unconventional cancer treatments (part 6 of 19)

Chapter 4

Herbal Treatments

CONTENTSPage

Chaparral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70Essiac . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Background and Early Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .*. .**.**.***.*.*.**.* 71Rationale for the Treatment and Claims for Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72Components of Essiac . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Attempts at Evaluating Essiac in Cancer Patients . . . . ... ,.. .. . $ . . ., . * * * . . . . . . . . . . . 74Current Status of Essiac in Canada . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74

The Hoxsey Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .*. . . . .**..*.**..**.***.*** 75Rationale for the Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76Components of the Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76Antitumor Effects of the Hoxsey Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77Adverse Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79claims . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79Attempts at Evaluating the Hoxsey Treatment . . . . . . . . . . . . . . . . .*.**,.**..*****.*+. 79

Mistletoe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .81Steiner’s Approach to Cancer Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .82Preparation and Administration of Iscador ● ... ..*. **. *.. *.*. .. * * $ . * . * . . . . *.*....** 83Indications for Use **. ... ... ... **. ... ..*. *.. ... ... ... ... .*. *.. . * $ * . * * * * * **@....** 83Effects of Iscador Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....84Mode of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .85Studies of the Biological Activity of Iscador . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85Clinical Studies With Iscador . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

Pau D’Arco . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

Chapter 4

Herbal Treatments

The therapeutic use of plant products—herbalmedicine-is among the oldest of medical practices.It is a central feature of many current forms of folkand traditional medicine, e.g., traditional Chinesemedicine, Native American healing, and curander-ismo, and is used in the treatment of a wide range ofdisorders, including cancer, More than 3,000 differ-ent plant species have reportedly been used to treatcancer in cultures worldwide, according to a surveyof the international literature (through 1971) inscientific and folk medicine (382). Herbal productsare also used in unconventional cancer treatment inthe United States, drawing from traditional practicesin most cases, but generally offered outside of theoverall context of traditional medicine and folkhealing.

Plant products are also the source of much of themainstream pharmacopeia. The use of botanicalproducts in drug development involves the identifi-cation and extraction of active components of wholeplants or crude extracts and, in some cases, synthesisof equivalent active compounds. The rationale forthis approach is that by reducing or eliminating thevariability of chemical composition and concentra-tion that exists in crude plants, precise doses ofknown compounds can be given to patients.

Several chemotherapeutic drugs used in conven-tional cancer treatment were developed from botani-cal sources. One of the best known examples isEtoposide, derived from the mayapple plant (Podo-phyllum peltatum). Prompted by a 1942 report of thetreatment of venereal warts using a constituent(podophyllotoxin) of mayapple, Jonathan Hartwelland colleagues at the National Cancer Institute’s(NCI’S) Drug Research and Development Programidentified the chemical structure for podophyllo-toxin and isolated other constituents of the plant(719). NCI conducted tests of the constituents forantitumor activity in a mouse tumor model (theSarcoma 37 test), and found that all were highlyactive in that test system (384). NCI initiated clinicaltrials of podophyllotoxin, which were later discon-tinued because of its toxicity. Clinical trials of thesubstance were continued by a private company(Sandoz Limited) in the 1960s, and semisyntheticcompounds (etoposide and teniposide) were laterdeveloped from the substance. Etoposide was ap-

proved by the Food and Drug Administration (FDA)in 1983 for use in patients with refractory testiculartumors, small-cell lung cancer, nonlymphocyticleukemias, and non-Hodgkins lymphoma (424).

Two of the most important chemotherapeuticdrugs currently used were originally developed froma folk remedy containing the rosy periwinkle plant(Vinca rosea), which was used in Madagascar fortreatment of diabetes. Chemical constituents withantitumor activity were isolated from the plant andtested for antitumor effects in animal systems. Theconstituents were later approved as vinblastine, usedto treat Hodgkins disease, and vincristine, used totreat acute childhood leukemia (826).

Traditional herbal practices, in contrast, involvethe use of whole plants or crude extracts of wholeplants, rather than purified active components. Oneof the central tenets of herbal philosophy is thatconstituents in botanical preparations other than thepredominant active component may modify physio-logic effects of the active component in beneficialways (945). The effects of crude preparations aregenerally slower in onset and less dramatic thanthose of the purified active ingredient, which maybeconsidered advantageous in some instances (946).

In recent years, some aspects of traditionalChinese medicine involving herbal medicine, acu-puncture, Qi gong, and other practices, have becomemore popular in the United States and are used totreat a wide variety of conditions. U.S. cancerpatients who use traditional Chinese medicine do somainly for pain control, reduction in side-effects ofconventional treatment, and enhanced quality of life,in the opinion of several members of the AdvisoryPanel for this project (8). Some of the herbalproducts used in traditional Chinese medicine aresold in U.S. health food stores and by specialtysupply companies (948). In China and Japan, wheretraditional chinese medicine and, particularly, herbalmedicine, is used in primary antitumor treatment,herbal products are the subject of much scientificresearch concerning their role in host support, e.g.,as enhancers of immune function (207). Most of therecent scientific literature on immune-stimulatingeffects and adjunctive therapeutic use of herbal

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70 ● Unconventional Cancer Treatments

medicine in cancer treatment has been published byresearchers in China, Japan, and Korea.

Higher fungi, including both edible and inediblemushrooms, are some of the major sources ofpolysaccharides and other substances that have beenstudied for antitumor and immunologic activity andas potential sources of new anticancer drugs. Manytypes of fungus are used medicinally in China andJapan to stimulate host defenses and to enhancepatients’ overall health. One of the most extensivelystudied mushrooms is the shiitake (Lentinusedodes), a popular edible mushroom in Japan.Lentinan, a polysaccharide isolated from extracts ofthe shiitake, has shown antitumor activity in avariety of animal tumor tests and has shown a varietyof immune-altering functions, e.g., as a restorer orpotentiator of T-lymphocyte activity, with no directcytotoxicity (182). Another example includes ex-tracts from the underground tuberlike growths (scle-rotia) of Polyporus umbellatus, an edible mushroomthat grows wild on tree stumps. Studies have shownthat a polysaccharide found in extracts of Polyporusumbellatus increases cellular and humoral immuni-ties in experimental animals, is active in experimen-tal tumor systems, and may potentate the effects ofchemotherapy (375). Other fungi studied for immu-nologic and antitumor effects include Coriolusveriscolor, from which the polysaccharide Krestin isderived, and the enokidake fungus (Flammulinavelutipes). Clinical studies in Japan and China havealso examined the potential for using extracts ofsome fungi in conjunction with conventional cancertreatment (207,375).

A small number of botanical preparations arecurrently being used to treat cancer in a way that isdistinct both from the context of traditional herbalpractices and from conventional drug development.Some of them may have had roots in traditionalpractices, but have since been removed from thatcontext and offered independently or in conjunctionwith conventional cancer treatments by practitionersuntrained in traditional medicine. These few herbaltreatments can be included in this report, since intheir present form, they are neither a part ofconventional cancer treatment nor of traditional orfolk medicine.

This chapter summarizs the available informa-tion on five of the most widely used unconventionaltreatments based on herbal substances (presented inalphabetical order). These include single agenttreatments, such as teas brewed from chaparral andPau d’Arco, and mixtures of herbal products sold asproprietary treatments-Hoxsey products, prepara-tions of mistletoe, and Essiac treatments.

CHAPARRALChaparral is an herbal product commonly avail-

able in health food stores. There is little systematicinformation available on its use, but it is oftensingled out, along with Pau D’Arco and severalothers, as a widely used unconventional treatmentfor cancer. Chaparral tea has reportedly been used infolk remedies for leukemia and cancers of thekidney, liver, lung, and stomach (382). It is reportedto have been popular among American Indians of theSouthwest as a remedy for a wide variety ofdisorders in addition to cancer, such as arthritis,venereal disease, tuberculosis, bowel cramps, rheu-matism, colds, and bronchitis (266). Chaparral tea isclaimed to have a variety of medicinal qualities—it has been described as an analgesic, an expectorant,an emetic, a diuretic, and an anti-inflammatorysubstance (861).

Chaparral tea is prepared from the leaflets andtwigs of Larrea divericata Coville and/or Larreatridentata Coville, also known as the creosote bush(520), which is indigenous to the desert areas of theSouthwestern United States. According to onereport, the tea is made by steeping about 7 to 8 gramsof dried leaves and stems of chaparral per quart ofhot water (809).

A number of chemicals, e.g., gums and resins,have been isolated from the creosote plant. Studiesof its biological activity have focused on one of itsmain components, nordihydroguaiaretic acid (NDGA),a chemical with antioxidant properties that has beenused widely in the food industry as a preservative.1

A 1969 report by Smart and colleagues (809)summarizing the available scientific data on NDGAnoted that in vitro tests revealed a‘ ‘virtual completeinhibition of aerobic and anaerobic glycolysis and

l~ong & bi~l~gi~~ proWfies of -A is ~ it Mbits ~sp~ation in ce~ types of ceus; this ~tioxitit characteristic w=, ~til 1967, USedas the rationale for the food industry’s using NDGA as a food additive to prevent fermentation and decomposition of commercial foods. In 1968, theFDA removed NDGA from its “generally recognized as safe” (GWS) list after the results from long-term feeding studies in rats showed that NDGAinduced lesions inmesenteric Iymphnodes and kidneys. The U.S. Department of Agriculture, however, still permits the use of NDGA in lard and animalshortenings (861).

Chapter 4--Herbal Treatments ● 71

respiration with dilute suspensions of Krebs 2ascites, Ehrlich ascites, and leukemia L121O cells. ’Some in vitro studies reported that NDGA wasassociated with stimulation of tumor cell growth andstimulation of respiratory enzyme activity at lowconcentrations, though those same processes wereinhibited at higher concentrations of NDGA (810).It has also been reported that under certain condi-tions, NDGA can bind to DNA (932) and cansuppress certain immune responses in culturedmouse cells (783).

NDGA had sigificant antitumor activity in oneanimal tumor model (Ehrlich ascites tumor) whengiven with high doses of ascorbic acid (vitamin C),but has shown no activity in several other animaltumor models (S180, mammary adenocarcinoma755, and leukemia L121O in mice). Additional testsof extracts of the crude chaparral plant and of NDGAfor antitumor activity in animal models showed nosignificant antitumor effects, with the “possibleexception of a flavonoid fraction of L. divaricatawhich had marginal activity in P388" (383). Ac-cording to NCI, additional animal tumor tests carriedout at the University of Utah reportedly showed thatNGDA was active in the ependymoblastoma testsystem but not in Melanoma S91 tumors (810).NDGA has also been reported to inhibit the develop-ment (59 1) and promotion (57) of certain carcinogen-induced tumors in rodents.

Based on a 1969 case report (809) of a patient withrecurrent malignant melanoma whose cancer report-edly regressed following treatment with chaparraltea, and on some of the experimental data citedabove, NCI sponsored a clinical study of NDGA(810). It was reported that over a period of 1 year(November 1969 to November 1970), 59 patientswith ‘advanced incurable malignancy were treatedwith chaparral tea or NDGA at the University ofUtah. The treatment examined in the study includedboth chaparral tea as used by cancer patients and itscomponent, NDGA: some patients drank two tothree glasses per day of chaparral tea, while othersreceived oral doses of pure NDGA (250 to 3000 mgper day). It was not noted in the analysis whichpatients took which form of the treatment. Theoutcomes of 45 of these patients were consideredevaluable (defined as having received at least 4weeks of treatment or as having undergone a tumorregression of at least 25 percent or more), althoughfew clinical details were given in the publishedreport.

Tumor remissions were reported in four patientsin that study. One was the case previously describedof the man with recurrent melanoma (his inclusionin the results indicates that the study was not entirelyprospective) (see ch. 3). Another was a secondpatient with melanoma (in these two cases ofmelanoma, the duration of response was noted as 3months and 20 months). The third was a patient withchoriocarcinoma of the testicle with pulmonarymetastasis, whose regression lasted 2 months, and afourth was a patient with lymphosarcoma, whoseregression lasted 10 days. Little additional clinicalinformation about these patients, e.g., previoustreatment or stage of illness, is given in the report. Itwas noted that 27 of the patients had “subjectiveimprovement” during the course of their treatmentwith chaparral tea or NDGA.

While the authors concluded that chaparral teawas not an effective anticancer agent (defined in thereport as a substance that caused a significantregression of 20 percent of a specific cancer typelasting a minimum of 2 months), the report indicatesthat there could have been evidence of someantitumor activity. The lack of clinical detail in thepublished report makes the results difficult tointerpret, but the observation that several patientswith advanced disease had tumor regressions sug-gests that chaparral tea and NDGA as given were notnecessarily inactive.

ESSIACEssiac is an herbal preparation developed in

Canada as a treatment for cancer, which is reportedto have originated in Indian folk medicine. From the1920s until the late 1970s, Essiac was made avail-able to cancer patients by Rene M. Caisse, a nursewho developed the treatment while working at amedical clinic in rural Ontario and who became itssole proprietor. Shortly before her death in 1978,Caisse turned over the Essiac formula, along withrights to its name and manufacture, to the ResperinCorp. of Ontario, the company currently providingEssiac to patients in accordance with a specialagreement with Canadian federal health officials.

Background and Early Use

Rene Caisse began her career as a public healthnurse in Haileybury, Ontario. In 1922, one ofCaisse’s patients told her that she had recoveredfrom breast cancer some 20 years earlier after takingan Indian herbal tea. Caisse obtained the recipe for


the herbal tea and began administering it to cancerpatients in 1924 following a reportedly successfultreatment of a relative with cancer using the tea. Shenamed the treatment Essiac, her name spelledbackwards. She gradually modified the herbal for-mula, producing an injectable and an oral form of thetreatment. One of the constituent herbs, whichCaisse believed had antitumor effects, was used inthe injectable form, while three other herbs, whichshe believed contributed to improvements in overallhealth rather than to tumor reduction, were used inthe oral form (303). She never revealed the names ofthese herbs, nor any others she may have used.Throughout her career, Caisse insisted that theingredients and formula remain secret, despitepressure from the public and medical profession toreveal the information (303).

From the late 1920s until 1942, Caisse operated aclinic in Bracebridge, Ontario (303), where shetreated hundreds of cancer patients with Essiac(388). From the 1950s until her death in 1978, sheprovided patients with Essiac from her home inBracebridge, except for a period of unknown dura-tion beginning in 1959 when she worked at theBrusch Medical Centre in Boston (303).

OTA research did not turn up any papers byCaisse in the scientific or popular literature. Most ofthe available written information on Essiac comesfrom the press, which, since the 1920s, has periodi-cally described certain aspects of Caisse’s career, heradvocacy of Essiac as a cancer treatment, andtestimonials of patients treated with Essiac. Most ofthese articles have appeared in local Ontario news-papers. 2 In 1977, an investigative article entitled‘‘Could Essiac Halt Cancer?’ was printed in Home-maker’s, a popular Canadian magazine (303). Morerecently, the identity of herbs used in Essiac has beenreported (388,981), but few additional treatmentdetails have come to light. No substantive informa-tion about the treatment regimen is available in theArchives of Ontario (Ministry of Culture andCommunications, Toronto, Ontario), where copiesof some of Caisse’s personal correspondence be-tween 1938 and 1959 are kept.

The description provided here is based on thesefew sources; most of these are secondary sources,since neither Caisse nor her supporters have appar-

ently provided any primary materials. OTA’s re-quests for primary written information from theOntario company currently supplying Essiac andfrom Canadian health officials now coordinating theprovision of the treatment were refused.

Rationale for the Treatment and Claimsfor Efficacy

The 1977 Homemaker’s article briefly describedCaisse’s view of how she thought Essiac affected thecancer process, based on her observations of patientswho took the treatment:

Often patients would report an enlarging andhardening of the tumor after a few treatments; thenthe tumor would begin to soften, and if it was locatedin any body system with a route to the exterior, thepatient would report discharging large amounts ofpus and fleshy material. After this, the tumor wouldbe gone. Rene reasoned that Essiac somehow causedall the cancerous cells to retreat to the site of theoriginal tumor, then to shrink and discharge-oftento vanish altogether. (303)

Caisse claimed that even in what she referred to as‘‘hopeless’ or “terminal” cases, Essiac benefitedpatients by relieving pain, reducing tumor size, andincreasing survival. She claimed generally positiveresults with many types of cancer with no harmfulside effects (303). She reportedly also believed thattreatment with Essiac would reduce the risk ofmetastasis following surgery to remove tumor tissue(303). In a letter to the Deputy Minister of Health inCanada dated October 6, 1958, Caisse wrote:

My treatment consists of an intermuscular injec-tion of herbs which causes the growth to localize. Ifthere are secondaries, they recede into the primarygrowth, causing it to become larger, until it is alllocalized; then the mass starts to reduce in size. (148)

According to a current patient information sheetdistributed by a cancer support group, Essiac in-creases appetite, “alleviates and can eliminatepain,” and “gives a wonderful feeling of well-being.’ It is claimed to be nontoxic and to have noside-effects.

There is no available information to indicate howCaisse applied Essiac in specific cases, e.g., whethershe gave all patients the same doses of the sameformula or whether she modified the treatment

@lany of these are collected by Stan Darling, Member of Parliment, Ottawa, Ontario. One recent newspaper example is: J. Lun& “The OjibwayWonder Drug, Can Essiac Cure Cancer?” Norrh Buy Nugget, Apr. 9, 1988 (570).


regimen (ingredients, treatment schedules, oral v.injectable forms, etc.) for different patients. Atpresent, Essiac is sold in 16 oz. bottles, withrecommended doses of 2 oz. diluted in 2 to 3 oz. ofwarm water to be taken once a day for the first 10days, later reduced to 1 oz. in the same dilution perday. This dose is recommended for 1 to 2 years orlonger, with amounts eventually being further re-duced to two or three times per week (449). Thepatient information advises that no other treatment,including chemotherapy and radiation, should beused while taking Essiac. It states that “any othertreatment which causes change in the human im-mune system will prevent Essiac from doing itsjob.” If other medication must be taken, however,Essiac “will not conflict,” it just won’t “work asfast” (449), according to current patient informa-tion.

Components of Essiac

Several reports specify four herbal ingredients inEssiac: Indian rhubarb (Rheum palmatum), sheeps-head sorrel (Rumex acetosa), slippery elm (Ulmusfulva),and burdock root (Arctium lappa) (388,392,981).None of these reports indicate how or when theseingredients were identified, although one (98 1) citespersonal communication from the Resperin Corp.No information is available on the amount of eachingredient or the method of preparation, sinceResperin considers the formula proprietary.

Some experimental antitumor data are availableon the individual herbal ingredients reportedlypresent in Essiac mixture. As with the Hoxsey datadescribed later in this chapter, OTA obtained infor-mation about antitumor testing of the Essiac ingredi-ents from the Natural Products Branch at NCI (232)3

and from the published literature (as collected by theNAPRALERT database,4 various books, and scien-tific articles). The details are summarized below:

Burdock—Two studies reported antitumor activ-ity of burdock in animal tumor systems (257,296),while two others reported no significant activity forthis herb (451,969). NCI tested burdock 14 times,with one sample showing activity, though notconsidered significant, in the P388 mouse leukemiasystem. Benzaldehyde, which has been isolated from

burdock, has shown antitumor activity in someanimal tests.

Indian rhubarb-This herb was found to haveantitumor activity at one dose level in the Sarcoma37 animal system but not at a higher dose in the sametest system (72). Another group found Indianrhubarb inactive in two other animal tumor systems(485). NCI tested two samples of Indian rhubarbfrom Poland and found no antitumor activity inmouse leukemia systems. Another type of Indianrhubarb, Peltiphyllum peltatum, was tested threetimes at NCI using samples from California, andnone was found active in mouse leukemia systems.Components of Indian rhubarb, e.g., aloe emodin,catechin, emodin, and rhein, have shown antitumoractivity in some animal test systems.

Sorrel—NCI tested one sample of sorrel fromTaiwan and found no activity in mouse leukemiasystems. The compound aloe emodin and emodinhave been isolated from sorrel and have shownactivity in some animal test systems.

Slippery elm—NCI tested slippery elm seventimes using samples from various parts of the UnitedStates and found no antitumor activity in mouseleukemia systems. Slippery elm contains beta-sitosterol and a polysaccharide, both of which havebeen reported to have antitumor activity in animaltumor models.

Unlike the Hoxsey treatment (see below), whichhas not been tested as a mixture for antitumoractivity in animals, the presumably complete Essiacmixture has been tested for antitumor activity in avariety of experimental mouse tumor systems. Theseexperiments were conducted at Caisse’s request bythe Memorial Sloan-Kettering Cancer Center(MSKCC) in the mid- 1970s and again at MSKCC atthe request of the Resperin Corp. in the early 1980s((427). In 1983, Canadian federal health officialsrequested that NCI test Essiac for antitumor effectsin animals (359,602).

Caisse submitted three samples of Essiac (twodried samples used to make an extract and one liquidsample), which MSKCC tested in the S-180 mousesarcoma test system. This test is intended to detectimmunotherapeutic effects (indicated by the occur-

s~se data ~e upublishe~ though publicly available from NCI on quest.ANa~~ Product Data Base, Program for Collaborative Reseamh in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at

Chicago. The NAPRALER T database systematically collects information about natural products from the published literature.


rence of tumor regression) or chemotherapeuticeffects (indicated by a diminished tumor growthrate) (427). The results of six immunotherapy testsand two chemotherapy tests of Essiac samples usingthe S-180 system all showed no activity. MSKCCtested Resperin’s sample of Essiac in a variety ofother animal leukemia and solid tumor test systemsin 17 separate chemotherapy experiments and foundno antitumor activity in any of these tests. Noevidence of acute toxicity was found in any of thesetests, although some evidence of subacute toxicity(slight weight loss in treated animals) was found(427).

In 1983, the Resperin Corp. submitted a liquidEssiac sample to NCI, following a request from theHealth Protection Branch, Health and WelfareCanada, that Essiac be tested in animal systems. Theresults of NCI’S tests with Essiac showed noantitumor activity in the mouse lymphocytic leuke-mia P388 tumor system. In contrast to the MSKCCtests, however, NCI found lethal toxicity in thehighest concentrations of Essiac given to the animalsin these tests. It is not known how the compositionof MSKCC’s samples compared with NCI’s sam-ples, or how the concentrations used in the animaltests relate to those in the treatments given topatients.

Attempts at Evaluating Essiac inCancer Patients

There have been no prospective clinical trials ofEssiac to determine its safety and efficacy as acancer treatment. In the early 1980s, however,Canadian health officials conducted a retrospectivereview of Canadian patients treated with Essiacusing case summaries submitted voluntarily by thepatients’ physicians. In 1982, when the reviewbegan, about 150 physicians in Canada had report-edly requested supplies of Essiac on behalf of theircancer patients. On request from the government,approximately half of these physicians submittedsummaries on a total of 86 patients to the Canadianfederal health department (Bureau of Human Pre-scription Drugs, Health Protection Branch, Healthand Welfare Canada). According to the formerdirector of the Bureau of Human Prescription Drugs(392), the Bureau reviewed the physicians’ reportsand concluded the following:

47 patients received “no benefits” from Essiactreatment;

8 of the patient reports were unevaluable;17 patients died;

1 had a‘ ‘subjective improvement”;5 required fewer analgesics;4 had an “objective response” to the treatment;4 were in “stable condition. ”

The Bureau’s judgments were based on thewritten summary comments physicians submitted,not on a review of the original patient charts. TheBureau did solicit additional information on the fourpatients who reportedly had an objective responseand the four who were in stable condition. Amongthese eight patients, three were then found to havehad progression of disease, two had died, and threewere still in stable condition. The latter threepatients had received previous conventional treat-ment that, in the Bureau’s judgment, was probablyresponsible for their stable condition. The Bureauconcluded that this review provided no evidence thatthe progression of cancer in these patients had beenaltered by taking Essiac. It noted, however, thepossibility that some of these patients might havebenefited from the treatment psychologically oremotionally. The Bureau’s summary of the safetydata collected in that review noted that “withoccasional batches there was some nausea andvomiting’ ‘ and suggested that these reactions wereprobably due to “a variation in composition” of theherbal preparation. However, few patients report-edly experienced any serious side-effects from thetreatment.

Current Status of Essiac in Canada

In 1978, Resperin filed a “preclinical new drugsubmission” 5 with the Health Protection Branch(HPB), Health and Welfare Canada. HPB officialsallowed Resperin’s application to proceed, authoriz-ing the distribution of Essiac to “qualified medicalinvestigators’ for clinical trials designed to obtainscientifically valid data on Essiac’s safety, dosage,and effectiveness in cancer treatment (392). Inaddition, it was expected that the Resperin Corp.‘‘would maintain adequate manufacturing and qual-ity control of the drug” and would “undertakeappropriate scientific investigations to isolate andidentify any active substances] in Essiac” (392).


In September 1982, HPB suspended Resperin’spreclinical new drug submission. An HPB officialstated that Resperin had not fulfilled its commitmentunder the agreement “to maintain adequate manu-facturing, to investigate the pharmacology of Essiac,and to arrange appropriate clinical trials” (392).During the same period in which the Canadianpreclinical drug submission was in effect, Resperinapplied to FDA for an NDA-permission to marketEssiac in the United States-but this application wasturned down (554). Details of the NDA submissionare confidential, according to FDA rules, so nodetails on this application are available unlessResperin chooses to make them public.

Although Essiac is currently unapproved formarketing in Canada and cannot be used in clinicaltrials without a valid preclinical new drug submis-sion, the Canadian Government allows Essiac to bemanufactured and sold, and to be used by cancerpatients under certain circumstances. A cooperativearrangement between Resperin and HPB authorizesthe distribution and sale of Essiac to cancer patients“on compassionate grounds,” i.e., when no othertreatment is appropriate in the particular case (392).Patients who wish to obtain Essiac ask their physi-cian to make a request to the Bureau of HumanPrescription Drugs, which relays the order to thecompany, and the company ships Essiac directly tothe patient. Physicians are asked to report to HPB theclinical details on each patient using Essiac. OTArequested details from HPB about its procedures fordistributing Essiac and monitoring its use (e.g., thetype of data collected, how many patients haverequested and received Essiac from Resperin viaHPB over the past 5 years, how many of these areU.S. patients, and the types of cancer for whichtreatment with Essiac is being sought), but was toldthat no more information could be given (480).

THE HOXSEY TREATMENTThe Hoxsey treatment involves several herbal

preparations, all of which are made from combina-tions of herbs and inorganic compounds. At present,this treatment is offered only at a clinic in Tijuana,Mexico, although from 1924 until the late 1950s(188) it was offered at a number of clinics in theUnited States under the direction of the late HarryHoxsey (1901-1974). Awareness of the treatmentwas recently renewed by the release of Hoxsey:

Quacks Who Cure Cancer? (59), a documentary filmon the history of the Hoxsey treatment and on HarryHoxsey’s personal role in its development andpromotion.

According to Hoxsey’s autobiographical bookYou Don’t Have To Die (418), the herbal formula forthe Hoxsey treatment was developed in 1840 byJohn Hoxsey, Harry Hoxsey’s great-grandfather. Itwas derived from grasses and flowering wild plantsgrowing in a pasture where one of John Hoxsey’shorses, afflicted with a cancerous growth, grazeddaily. The horse’s cancer reportedly disappeared,and John Hoxsey surmised that the wild plants hadcaused the recovery. He gathered some of the plantsfrom the pasture, and later added ingredients fromold home remedies for cancer. He used the resultingherbal mixture to treat similarly afflicted horses nearhis farm in southern Illinois (418,938).

The herbal formula was bequeathed to JohnHoxsey’s son, then to Harry’s father John, andfinally to Harry Hoxsey in 1919, whose fathercharged him with using it to treat cancer patients “ifneed be, in defiance of the high priests of medicine’(418,984). Although Harry’s father, a veterinarysurgeon, was the first to use the formula to treatpeople with cancer, it was Harry Hoxsey who madeit famous. The first clinic offering the Hoxseytreatment opened in the early 1920s and by the1950s, the Hoxsey Outpatient Clinic in Dallas wasreportedly one of the largest privately owned cancercenters in the world (188), with branches in 17 States(58). By Hoxsey’s account, the clinic had at its peakof operation 10,000 patients “under constant treat-ment or observation” (418,582).

Hoxsey was widely known for his flamboyant andconfrontational style (59,938,984). His reluctance todisclose the treatment formulas and his bold claimsreportedly led Morris Fishbein, then editor of theJournal of American Medical Association (J.A.M.A.),to publish articles labeling Hoxsey and his late fatheras charlatans (938). Hoxsey sued for libel and won(984).6 In 1956, the FDA Commissioner ordered thata “Public Beware!” warning against the Hoxseytreatment be posted in U.S. Post offices andsubstations across the country (518,984). Repeatedclashes with FDA over violations, and a number ofarrests eventually prompted Hoxsey to close hismain Dallas clinic in the late 1950s.

%e history of Hoxsey’s legal battles with the American Medical Association has been extensively reviewed elsewhere. See, e.g., (294,418,984).


Since 1963, the Hoxsey treatment has beenoffered at a clinic in Tijuana, Mexico, under thedirection of Hoxsey’s longtime chief nurse, MildredNelson (58). The herbal preparations Nelson uses totreat cancer patients are reportedly based onHoxsey’s herbal formulas and method of preparation(78,188).

Rationale for the Treatment

In 1956, Hoxsey described his belief that cancerwas a systemic disease, however localized itsmanifestations might appear to be. Although he didnot ‘‘pretend to know its fundamental cause, ’ hebelieved that “without exception it occurs only inthe presence of a profound physiological change inthe constituents of body fluids” and that it leads toa “chemical imbalance in the organism” (418).Hoxsey summarized the theory behind his approachthis way:

We believe that the organism’s attempt to adaptitself to the new and abnormal environment pro-duced by the chemical imbalance causes certainchanges (mutations) in newly born cells of the body.The mutated cells differ radically in appearance andfunction from their parent cells. Eventually a vi-ciously competent cell evolves which finds the newenvironment eminently suitable to survival and rapidself-reproduction. These cells are what is known ascancer.

It follows that if the constitution of body fluids canbe normalized and the original chemical balance inthe body restored, the environment again willbecome unfavorable for the survival and reproduc-tion of these cells, they will cease to multiply andeventually they will die. Then if vital organs have notbeen too seriously damaged by the malignancy (orby surgery or irradiation) the entire organism willrecover normal health. (418)

He also did not claim to know how or why hisherbal cancer treatment worked, but he maintainedthat it “corrects the abnormal blood chemistry andnormalizes cell metabolism” by “stimulat[ing] theelimination of toxins which are poisoning thesystem” (418).

There are three external forms of the Hoxseytreatment used for tumors in or near the skin to ‘haltthe spread of the disease and speed the necrosis(death) of cancer cells” (418). Hoxsey reported thathis yellow powder is “highly selective” for malig-nant tissue, leaving normal tissue undamaged. Thepaste and liquid forms, however, were not, by his

account, selective. He applied vaseleline or zinc oxidearound the perimeter of the affected area, a practicewhich he believed contained the corrosive action ofthe preparations (418). Hoxsey summarized theobserved outcomes of his external treatment thisway:

In practice we have found that a small amount ofour compounds, when placed on a large cancerousmass, cause a chain reaction which extends an inchor two beyond the point of application. The massdies, dries, separates from normal, healthy tissue andfalls out. (418)

Nelson believes that the Hoxsey tonic “normal-izes and balances the chemistry within the body,” aprocess she believes results in tumor regression.

In a 1984 interview, Nelson said:

When you get everything normalized, the abnor-mal cells-the tumor cells--cease to grow. And veryslowly the tumor is absorbed and excreted, and it’sgone. (188)

In that same article, it was noted that the Hoxseytonic is intended to help “eliminate toxins from thebody.” In addition, the Hoxsey powder and pastewere described as “escharotic agents’ that werecommonly used by conventional physicians to treatcancer before radiation and chemotherapy weredeveloped (188).

Components of the Treatment

Hoxsey’s treatment regimen included his internaland external preparations and “supportive treat-ment,’ although the components of the latter are notspecified in his book (418). His preparations in-cluded a paste or salve applied topically for externalcancers; a powder, pills, and a dark brown herbaltonic taken orally. Hoxsey adjusted the compositionand dose of each patient’s formula, depending on theindividual patient’s general condition, the locationof the cancer, and the extent of previous treatment.The internal treatment was taken by mouth as aliquid tonic or in pill form (418).

Hoxsey’s 1956 book You Don’t Have To Die liststhe ingredients of his internal treatment given in “allcases of cancer, both internal and external” (418) aspotassium iodide combined with some or all of thefollowing substances, on a case-by-case basis:licorice, red clover, burdock root (Arctium lappa),stillingia root (Stillingia sylvatica), berberis root(Berberis vulgaris), pokeroot (Phytolacca ameri-


cana), cascara (Rhamnus purshiana), Aromatic USP14 (artificial flavor), prickly ash bark (Zunthoxylumamericanum), and buckthorn bark (Rhamnus fran-gula) (418). The last two substances in this list arenot specifically mentioned in Mildred Nelson’s listof ingredients used in the Hoxsey treatment shecurrently offers.

Hoxsey’s escharotic preparations, which wereapplied locally in “external cases,” included ayellow powder, a red paste, and a clear solution. Hereported that his yellow powder contained arsenicsulfide, talc, sulfur, and what Hoxsey called a“yellow precipitate” (664).7 The caustic red pastereportedly contained antimony trisulfide, zinc chlo-ride, and bloodroot (Sanguinaria canadensis). Theclear solution contained trichloroacetic acid (418).

The current Hoxsey treatment offered by MildredNelson at the Bio-Medical Center in Tijuana in-cludes a liquid tonic, a salve, and a powder, all ofwhich are reportedly based on Hoxsey’s formulas.The current patient literature from Nelson’s cliniclists the components of the liquid herbal tonic as:“potassium iodide and herbs, licorice, red clover,cascara, burdock root, barberis root (sic), poke rootand stillingia root’ (78). The ingredients of the salveand powder are not given. In addition, Nelson’streatment regimen specifically includes nutritionalsupplements and dietary restrictions. Nelson advisesbefore-meal “tri-tabs,” after-meal tablets, yeasttablets, vitamin C, calcium capsules, laxative tab-lets, antiseptic douches, and antiseptic washes. Shealso recommends that patients exclude certain foodsthat “nullify the tonic” (663), such as pork,tomatoes, pickles or other products with vinegar,salt, sugar, artificial sweeteners, alcohol, carbonatedbeverages, and bleached flour. All patients are testedfor systemic infection with the fungus Candidaalbicans before treatment is initiated, although thereasons for such testing are not given in the patientliterature (78). Treatment lasts up to 3 days at theclinic, with followup visits within 3 to 6 months afterthe initial visit.

Antitumor Effects of the Hoxsey Components

Many of the constituent herbs in the Hoxseytreatment have a long history of folk use in thetreatment of cancer, as well as for a variety of otherconditions (266,382). One of the constituents of the

external treatment, bloodroot (Sanguinaria cana-densis), was used by Native Americans to treatcancer, warts, and nasal polyps.

The ingredients used in Hoxsey’s external paste-zinc chloride, antimony trisulfide, and bloodroot(418)-were used by Frederic Mohs, M.D., of theUniversity of Wisconsin Medical School in the1930s and 1940s to treat nonmelanoma skin cancer,e.g., invasive basal cell carcinoma. The Mohschemosurgical technique, as it came to be known,used the caustic paste to permit serial microscopicexamination of excised tissue (625). Mohs’ prepa-ration, which he referred to as a zinc chloridefixative, reportedly contained 40 grams of stibnite(antimony trisulfide in a metallic base), 10 grams ofpowdered sanguinaria, and 34.5 cc of a saturatedsolution of zinc chloride (624). In this method,dichloroacetic acid was first applied to the skincovering the tumor, followed by application of thecaustic paste to kill and fix the tissue, and left inplace under a bandage for 24 hours, during whichtime the patient was given analgesics for pain.Twenty-four hours later, a layer of tissue approxi-mately 5 millimeters thick could be excised with ascalpel, a procedure involving no pain or bleeding,and then examined microscopically. Several succes-sive applications of fixative, excisions, and micro-scopic observation were performed until the tumorwas removed.

Mohs reported high rates of success with thismethod-e. g., a 99 percent cure rate for all primarybasal cell carcinomas he treated (625). He noted thatthe reliability of the method was due to themicroscopic control that ‘‘makes it possible tofollow out the irregular and unpredictable exten-sions from the main tumor mass” (624). In a 1948paper in J.A.M.A., he contrasted his use of thefixative paste with that of unconventional practition-ers, who, according to Mohs, used the same fixativewithout microscopic control of excision, a procedureMohs considered unreliable and excessively muti-lating (624). In the early 1950s, Mohs and othersabandoned the use of the fixative paste in thismethod and replaced it with surgical excision offresh tissue specimens, which are then examinedmicroscopically as before. This latter form of Mohs’method is currently used in conventional surgicaltreatment of some types of skin cancer, particularly

7~~ @ht ~rre~p~nd to the ~~a fom @edients in &e book New C~re~@r O/dA~/~nts @~ on HOXSey Medicines) (664), listed as: flOWmelder, magnolia flower, blood roo~ and antimony trisulflde.

78 . Unconventional Cancer Treatments

basal cell and squamous cell carcinomas (845). Itsadvantages over the fixed tissue method reportedlyinclude the avoidance of pain associated with tissuefixation, the ability to perform multiple stages ofexcision in one day, and the elimination of ‘postfix-ation tissue slough, ’ permitting immediate recon-struction of the surgical wound when needed (845).

Over the past several decades, many of thebotanical products reported to be present in theHoxsey internal treatment have been tested individ-ually for antitumor activity in animal systems (seech. 12 for discussion of animal test systems). Thecomplete Hoxsey tonic currently given to cancerpatients has apparently not been tested for antitumoractivity in animal systems.

OTA obtained results of testing for antitumoractivity of the constituent Hoxsey herbs used in theinternal tonic from NCI’s Natural Products Branch,*the NAPRALERT database,9 an OTA contractreport reviewing the history of the Hoxsey treatment(938), and other published sources. Details of theresults in animal test systems are summarized below,giving results for NCI and non-NCI tests separately:

Burdock—Two studies reported antitumor activ-ity (257,296) in animal tumor systems, while twoothers reported no significant activity for this herb(451,969). NCI tested burdock 14 times, with onesample showing activity, though not consideredsignificant, in the P388 mouse leukemia system.Benzaldehyde, a constituent isolated from burdock,has been reported active in two test systems in rats(848).

Buckthorn-Antitumor activity of a component(aloe-emodin) of buckthorn has been reported in theP388 tumor system (495) and in the Walker 256system (summarized in (384)) (the Walker 256 testwas later withdrawn from use because of problemswith its validity). Two other components, emodinand dihydroxyanthroquinone, may also have antitu-mor activity in animal systems. NCI tested buck-thorn in animal systems three times, with noantitumor results.

Cascara-Also contains aloe-emodin and emodin,which have shown antitumor activity in animal testsystems. No antitumor activity was found when a

powdered plant suspension of cascara was tested inthe Sarcoma 37 system (72). NCI tested cascara 16times and found no antitumor activity.

Barber~Two studies have reported antitumoreffects of substances isolated from barberry (415,702).NCI reported one test of barberry, which showed noantitumor activity.

Licorice—one study reported that licorice wasinactive in the Sarcoma 37 test system (72). NCItested licorice 19 times, with one sample showingactivity that was not considered significant. Benzal-dehyde and a number of other components (e.g.,fenchone, glycyrrhizin, indole, quercetin, and beta-sitosterol) have been isolated from licorice andfound to be active in animal test systems.

Red Clover—Red clover showed no activity whentested in the P388 system (254). NCI tested redclover 94 times, with one test showing activity thatwas not considered significant.

Pokeroot-One published study reported no sig-nificant antitumor activity of pokeroot in threeanimal test systems (Ehrlich ascites, LeukemiaSN36, and Sarcoma 180) (969). A component ofpokeroot is well-known, however, for its ability toinduce the proliferation and differentiation of lym-phocytes in the blood (720), a property that might berelevant to an immunologic response to cancer butwhich might not be picked up as positive activity inthese animal tumor models. NCI tested pokeroot forantitumor activity 43 times; in one of these tests,activity was reported in the Walker 256 system, butthis test system was later withdrawn because ofproblems with its validity.

Prickly Ash—No tests for antitumor activity ofprickly ash have been reported in the literature,although some of its components (e.g., chelerythrineand nitidine) have tested positive in animal systems.NCI tested this plant for antitumor activity fivetimes, with no positive results.

Stillingia—No tests of stillingia have been re-ported, although one of its constituents (gnidilatidin)has tested positive in animal systems. NCI has norecord of testing it for antitumor activity.

g~e= tim We unpublished, though publicly available from NCI on -est.%latural Product Data Base, Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at

Chicago.


Taken together, the data indicate that many of theherbs used in the Hoxsey internal tonic or theisolated components of these herbs have antitumoractivity or cytotoxic effects in animal test systems.The complete Hoxsey herbal mixture has not beentested for antitumor activity in animal test systems,with human cells in culture, or in clinical trials,however. It is unknown whether the individual herbsor their components that show antitumor activity inanimals are active in humans when given in concen-trations used in the Hoxsey tonic. It is also unknownwhether there might be synergistic effects of theherbs used together.

Adverse Effects

Hoxsey’s medical director stated in a 1952publication that no toxic reactions had been seen inpatients treated with the Hoxsey tonic, but he addedthat ‘the growth of a cancer can be stimulated if thetreatment is used improperly” (664). No furtherinformation about this possibility was given.

No side-effects or toxicities specifically resultingfrom the Hoxsey treatment have been reported in themedical literature. Side-effects of some of theindividual herbs taken alone, often in massive dosescompared to the amounts present in the Hoxseytreatment, however, have been reported (67,179,487,671,881). Pokeroot, a reported component of theliquid tonic, contains toxic mitogenic substances(agents that induce cell division and proliferation),and has been linked with poisoning, including somefatal episodes, in children and adults (266). Therelevance of these reports to possible toxicities of theHoxsey mixture depends on the amount of each herbpresent in the mixture (which maybe unknown) andthe total amount taken (which varies with eachpatient).

Claims

Nelson claims that about 80 percent of the cancerpatients who take her herbal treatment are cured(59). She believes that a “bad attitude” is usuallyresponsible for her “20 percent failure rate” (663),and that she can tell who is going to get well and whois not from their attitude when they first arrive at theclinic; a patient’s strong belief that the treatment isgoing to lead to recovery is the best predictor ofsuccess, she says.

Hoxsey’s public claims of his treatment’s effec-tiveness were similar to Nelson’s present-dayclaims. Hoxsey presented numerous case histories ofpatients treated at his clinic in his 1956 book (418).Additional case histories supporting his claims aredescribed in a 1954 publication by Defender Maga-zine (251). In his book, Hoxsey noted that cancerpatients sought his treatment “as a last resort.” Hewrote:

We don’t pretend to cure all of them. The vastmajority are advanced and even terminal cases by thetime we get them. Many come to us after the diseasealready has spread through the body; after surgery orirradiation has so impaired circulation of the bloodto the affected areas that our treatment cannot reachthem . . . Nevertheless we believe we cure a fargreater percentage of cases treated than is cured byany other method at present known to science. (418)

In 1947, the medical director of Hoxsey’s clinicstated it more specifically: he claimed they had beencuring ’85 percent of external cancers, and approxi-mately 25 percent of internal cancers’ (664). Inparticular, it was noted that the outcome of treatmentwas ‘dependent to a great extent upon the lymphaticsystem, and our best results are in cancers that havea large lymphatic supply.” He stated that many oftheir patients had had “the limit of X ray andradium” and “in many of these, we cannot hope tocure the cancer itself because of the extensive priordestruction,” but that the Hoxsey treatment might“limit the further extension of the cancer and keepthe patient free from pain thereafter.” This directornoted, “in almost every case that the general healthof the patient improves’ as a result of the treatment.He concluded that “we know that the Hoxseytreatment cures cancer, and it is only reasonable tobelieve that we have within our grasp the cause, andeventually the complete solution, of the cancerproblem” (664).

Attempts at Evaluating the Hoxsey Treatment

No clinical trials of the Hoxsey treatment havebeen reported. Several record reviews, initiated inthe 1950s, have been discussed in the literature,however. The first was based on a site visit in 1954by a group of physicians, who, by Hoxsey’s account,spent 2 days inspecting the clinic, reviewing patientrecords, and talking to patients. Although the data onwhich they made their conclusions are not given inHoxsey’s book where an excerpt of their statementappears, the group concluded that the Hoxsey Clinic


was “successfully treating pathologically provencases of cancer, both internal and external, withoutthe use of surgery, radium or x-ray” (quoted in(418)). Criteria for such successful outcomes report-edly included patients who remained “symptom-free in excess of five to six years after treatment. ”They concluded that “the Hoxsey treatment issuperior to such conventional methods of treatmentas x-ray, radium, and surgery. ”

In 1957, a committee of faculty members of theUniversity of British Columbia conducted a reviewof the Hoxsey treatment and facilities (582). Aftervisiting Hoxsey’s Dallas clinic, the committeedescribed the overall treatment regimen, along withvarious other aspects of the treatment (the history ofthe treatment, Hoxsey’s claims for efficacy, and thehistory of Hoxsey’s litigation concerning the treat-ment). They were particularly interested in follow-ing up on patients from British Columbia who weretreated at the clinic. The clinic gave the committeemembers records for 78 patients from their ‘active’fries (unbeknownst to the clinic, however, some ofthese patients had died). The committee was able tofollow up on 71 of these patients, using BritishColumbia’s cancer registry, death registry, andphysician records. Their detailed findings weresummarized as follows:

For over one-half of the [cancer] patients fromBritish Columbia, the result [of treatment with theHoxsey method] has been either death or progressionof the disease. In nearly one-quarter there was noproof that the patient ever had cancer. Nearly one inten of the patients had curative treatment beforegoing to the Hoxsey Clinic. In only one case, anexternal cancer, was there any evidence at all that theHoxsey treatment had an effect on the disease; in thatcase, better results could have been obtained byorthodox means. (582)

The latter case to which they refer reportedlyinvolved a woman with a “slow-growing cancer ofthe ear” who refused surgery and was treated withone of Hoxsey’s external treatments. The committeereported that the treatment ‘‘did, in fact, remove thecancerous growth, along with a good deal of normaltissue.’ It did so ‘‘with needless pain and disfigure-ment,” given that it could have been treated withradiation or surgery, in the committee’s opinion(582). They also reported that of the 32 patients whodied, “two-thirds were dead in less than six months,90 per cent were dead within a year, and nonesurvived two years” (582).

Hoxsey made attempts (in 1945 and 1950) to haveNCI review his patients’ records. On both occasions,NCI determined that the records Hoxsey submitteddid not meet NCI’S previously established criteria atthat time for documenting treatment effects. Insummary, these criteria required that Hoxsey:

●

●

●

explain the composition of his herbal treat-ments and his regimen for treating patients;submit complete clinical and laboratory recordsof at least 50 patients with internal cancer toshow conflation of the diagnosis by biopsyand objective evidence of regression of primarygrowth and metastasis by measurement, photo-graphs, and x-rays; andprovide proof that these patients had survived&least 5 years following treatment (418,582,984).

In 1945, Hoxsey reportedly submitted records for60 patients, 40 of which were for cases of externalcancer, and the remaining 20 were reportedlyunevaluable by NCI’s criteria (582,984). In 1950,Hoxsey submitted an additional 77 case histories, allof which, he claimed, were “fully documented withclinical records and pathological reports” and someof which included “actual microscopic biopsyslide[s]” or details of where NCI could obtain suchmaterial. He added that all but a few of the cases wesent in had been cured more than five years, andthose few were of a deadly type of cancer wheresurvival for even three years was considered littleshort of miraculous” (418).

According to a discussion of the documentationHoxsey submitted to NCI by the University ofBritish Columbia committee, however, Hoxsey’s 77records reportedly included only 6 biopsies; 2 ofthese were from patients with internal cancer andneither of these 2 biopsies confirmed the existenceof malignant cells (582,984). It was also reportedthat 31 of the 77 patients were dead within 5 yearsof treatment and ‘‘in the remaining 46 cases, thecriteria would have been met by 12 patients ifsuitable sections had been submitted” (582).

According to several sources, NCI concluded onthe basis of Hoxsey’s data that no assessment of histreatment could be made (418,582,984). Hoxseybelieved, however, that it was NCI’s responsibilityto verify his case records; their failure to do so wasdeliberate, he believed, resulting from a widespreadconspiracy organized against him by the AMA(418). Attempts were made to initiate investigationsinto Hoxsey’s treatment and his allegations against

Chapter 4--Herbal Treatments . 81

NCI and AMA, but the investigations were neverconducted. In 1947, Senator Elmer Thomas ofOklahoma asked the U.S. Public Health Service toinvestigate Hoxsey’s treatment, and the SurgeonGeneral refused the request (294,582,984). In 1951,Senator William Langer of North Dakota sponsoreda resolution under which a subcommittee wouldhave been authorized to study Hoxsey’s treatmentand claims for effectiveness, but this resolution wasnever reported out of committee (582,984).

Hoxsey’s point of view was echoed by a 1953report to the Senate Interstate and Foreign Com-merce Committee by Benedict Fitzgerald, an attor-ney who examined records of Hoxsey’s litigationwith the AMA and the Federal Government. Afterreading about the circumstances of these attemptedcase reviews, Fitzgerald wrote that NCI ‘‘took sidesand sought in every way to hinder, suppress, andrestrict [the Hoxsey Cancer Clinic] in their treatmentof cancer” (294). To date, no independent, com-prehensive assessment has been made to resolve themany allegations and issues raised by Hoxsey’stumultuous career.

MISTLETOEMistletoe has long been used in the treatment of

a variety of acute and chronic conditions (302). Itwas not widely used for treating cancer, however,until the 1920s, during the early development ofAnthroposophy, a modern “spiritual science” ap-plied to medicine and a variety of other disciplines.At present, mistletoe is given to patients either as thecentral component of a complex, broader treatmentregimen in the practice of Anthroposophic medicinemainly in Europe (277) or as a single agent partiallyor completely removed from the overall context ofAnthroposophic care (e.g., in the United Kingdomand other countries). At present, mistletoe prepara-tions are advocated mainly by Swiss and Germanphysicians practicing Anthroposophic medicine, butare also used by other European physicians notnecessarily associated with Anthroposophy. A largergroup of researchers in Europe, and to a lesser extentin the United States, has focused on the study ofmistletoe’s biological properties in various experi-mental systems.

Mistletoe preparations are available in a variety offorms (413,753), including a preparation by the tradename Plenosol (208), but the oldest and most widelyused is a product marketed by Weleda AG (Switzer-

land and West Germany) under the trade nameIscador, which consists of fermented extracts ofmistletoe, some forms of which are combined withsmall amounts of various metals (e.g., silver, copper,and mercury). Iscador is listed in the German RoteListe (1989) and is registered with the SwissInter-Cantonal Office for drug control (847), but isnot listed in the Swiss Compendium of pharmaceuti-cal drugs (224). Some commercial preparations ofmistletoe are licensed in West Germany, but are notheld to the same standards of efficacy as othermedical drugs (422), according to a 1976 WestGerman drug law (789) allowing for differentstandards for unconventional treatments.

Approximately 40,000 patients worldwide werereceiving Iscador treatment in the early 1980s,according to the Society for Cancer Research, aSwiss Anthroposophic organization (8 16). Mistletoetreatment is reportedly available in Switzerland,West Germany, the Netherlands, the United King-dom, Austria, and Sweden, at clinics and privatepractices specializing in Anthroposophic or in vari-ous types of “holistic” medicine. Commercialpreparations of mistletoe can be legally prescribedby licensed physicians in these countries (726). TheWeleda company, which makes a range of drug andhousehold products, also has branch operations inseveral other European countries, as well as inCanada, the United States, India, South Africa,Argentina, and Brazil (746). Although Iscador is notcommonly used in the United States, some U.S.physicians have been trained in Anthroposophicmedicine and incorporate aspects of its practice intopatient care (953). The U.S. branch of Weleda doesnot sell Iscador, as the product is not approved forsale in the United States, but U.S. physicians canorder Iscador directly from European manufacturers(952). Some U.S. patients may also travel tospecialized clinics or hospitals in Europe to receiveIscador treatment.

Mistletoe achieved prominence as a cancer treat-ment through the work of Rudolf Steiner, Ph.D.(1861 -1925), who founded Anthroposophy (598).Working with Ita Wegman, a Dutch physician,Steiner applied the principles of his “spiritualscience,’ which combined spiritual and scientificthought, to the practice of medicine and to thetreatment of cancer in particular. In the decadessince Steiner’s death, physicians and researchershave continued developing his ideas (423) and haveestablished a network of clinics and hospitals in


Europe, North America, and South Africa designedto put his principles into medical practice. The firstAnthroposophic clinics opened in Arlesheim, Swit-zerland, and Stuttgart, West Germany, in 1921. Agroup of physicians following Steiner’s philosophyfounded the Society for Cancer Research in 1935. In1949, that group founded the Hiscia Institute, whosemain purpose WaS to develop Iscador for therapeuticuse and to conduct research. The Lukas Klinik,specializing in the Anthroposophic treatment ofcancer, was opened in 1963 in Arlesheim. Atpresent, the Society for Cancer Research supportstwo research institutes (the Hiscia Laboratory,where Iscador is manufactured, and the WidarResearch Center, where biochemical studies ofmistletoe are carried out), in addition to the LukasKlinik and a postgraduate training facility forphysicians specializing incine.

Steiner’s Approach to

Steiner’s work led himresults from imbalances in

Anthroposophic medi-

Cancer Treatment

to believe that cancercertain forces affecting

the human body. He believed that some of theseforces are responsible for cell division, growth, andexpansion (“lower organizing forces”) and others(“higher organizing processes” or “formati“ve forces’are responsible for limiting and organizing thatgrowth, controlling cell differentiation, and produc-ing overall body form; it is the balance of these twotypes of force that influences the strength orweakness of one’s individuality. Steiner believedthat in healthy people, such forces are balanced andact in harmony, whereas in people with cancer or inpeople “susceptible” to cancer, the higher organiz-ing forces are weak, relative to the lower organizingforces. The resulting imbalance would lead to excessproliferation of cells, loss of form, and eventuallytumor production (477). Steiner believed that cancerinvolved not only physical disorder in the body, butalso disruptions among “different levels of matter,life, soul, and spirit” (726).

In the early 1920s, Steiner proposed mistletoe asa therapeutic agent capable of correcting the imbal-ance he believed was ultimately responsible for thedevelopment of cancer. In general, his proposal wasbased on the process of what he called “spiritualscience,’ in which he combined spiritual andscientific thought as “complementary” modes ofinsight. Anthroposophic literature refers to his

reportedly extraordinary mental capabilities (“higherfaculties of perception,’ extrasensory perception, orinner knowledge) as the key element underlying hisnovel proposal to use mistletoe therapeutically incancer (277).

Contributing to Steiner’s proposal to use mistle-toe were his detailed analyses of the plant’s botani-cal characteristics, which are described in manyAnthroposophic accounts of the origin of thistreatment. Steiner examined the growth and devel-opment of the semiparasitic mistletoe plant andnoted, e.g., that its morphology is spherical ratherthan vertical; its growth is not influenced by theforce of gravity; it grows on different species of hosttrees, taking water and minerals from the tree sapand supplying the tree with sugars made viaphotosynthesis; it avoids direct contact with theearth and makes no roots in the ground; it producesberries all year long; and it flowers in the winter.Steiner concluded from these characteristics thatmistletoe develops independently from earth forces(e.g., gravitational, electromagnetic, chemical) andfrom seasonal cycles, opposite to the way in whichhe believed tumors develop (94,477). Steiner con-cluded that these characteristics made mistletoeuniquely valuable as a therapeutic agent. He be-lieved that mistletoe could stimulate ‘higher organ-izing” or “individualistic” forces which he feltwere relatively inadequate in cancer patients. Hesuggested that by taking mistletoe, such forceswould be transferred from the plant to the patient andwould result in an enhancement of host inflamma-tory defense mechanisms against cancer. The mistle-toe treatment was named Iscador (94) and Steinerrecommended that the mistletoe be combined withcertain metals in high dilution that he believedwould enhance the activity of the mistletoe prepara-tion (847).

With Iscador as the central element, Steiner’scancer treatment regimen consisted of various medi-cal and nonmedical interventions. Steiner developedand advocated specific artistic activities that hebelieved also contributed to recovery from cancer,such as clay modeling, eurythmy (or movementtreatment), and speech formation. The overall aim ofthe regimen was to strengthen patients’ “formativeforces” or “organic self-supportive systems” andprovide an opportunity for individuals to undergoinner change and to develop the soul and spirit (533).


The current Anthroposophic treatment for cancerconsists of a similar, but expanded, combination ofinverventions intended to be used adjunctively withconventional care (726). Conventional medical treat-ment is recommended for some patients, although atthe Lukas Klinik in Switzerland, patients are gener-ally referred to other centers to obtain it. Treatmentat the Lukas Klinik consists of some combination ofthe following, according to each patient’s condition:conventional and homeopathic preparations for vari-ous medical problems associated with cancer (e.g.,for hemorrhages, bone metastasis, effusions, pain,etc.); a vegetarian diet with restrictions on theconsumption of mushrooms, hardened fats, refinedsugars, new potatoes, and tomatoes; avoidance ofalcohol and cigarettes; artistic activities such aseurythmy, painting, speech formation, light andcolor therapy, and music; light exercise; and hyper-thermic baths, oil baths, and massage (277,533,534).

Preparation and Administration of Iscador

Iscador is made from a species of Europeanmistletoe, Viscum album, which differs from mistle-toe commonly found in the United States. Thedifferent preparations of Iscador are classified ac-cording to the type of tree on which the mistletoegrows and are chosen for use according to the sex ofthe patient and the location of the primary tumor. Forinstance, “Iscador M“ refers to the preparationmade from mistletoe growing on apple trees, and isused to treat women with cancer; ‘‘Iscador Qu,’from oak trees, usually for men; “Iscador p,” frompine trees, for men and women; and “Iscador U,”from elm trees, for men and women (726,746).

The preparations are also distinguished by thetype of metal added, e.g., silver, mercury, andcopper, in concentrations ranging from 10-8g silver/100 mg mistletoe to l0-5g copper/100 mg mistletoe(746). The addition of these metals is believed toenhance the action of Iscador on particular organsand systems. An Iscador preparation with copper isused for primary tumors of the liver, gallbladder,stomach, and kidneys; Iscador with mercury is usedto treat tumors of the intestine and lymphatic system;Iscador with silver is used to treat cancers of theurogenital system and breast; and Iscador withoutany added metals is used to treat tumors of thetongue, oral cavity, esophagus, nasopharynx, thy-roid, larynx, and extremities (746). The rationale for

inclusion of metals with mistletoe preparations is notexplained in the Iscador literature OTA reviewed.

Some aspects of the method by which Iscadorpreparations are made are proprietary, but it isknown that the whole plant is used to make anaqueous extract, which is then fermented with thebacterium Lactobacillus plantarum. The fermentedsaps ofsummer and winter extracts of mistletoe aremixed and then undergo sterile filtration (413,955).It is packaged in small ampules containing differentconcentrations of mistletoe, ranging from 0.0001 mgmistletoe/ampule to 50 mg mistletoe/ampule, de-signed to be administered by subcutaneous injectionat or near the tumor site. In some cases, Iscador isadministered orally, e.g., in cases of primary tumorsof the brain and spinal cord.l0 A typical course ofIscador treatment consists of 14 injections given inincreasing concentrations. It is usually given in themorning, when body temperature is rising.

According to a report of the Swiss Cancer League(847), fermented Iscador products contain largenumbers of both dead and live bacteria (mainlyLactobacillus) and some yeast (847). Proponentscontest that assertion, noting that Iscador is filteredto eliminate bacteria and that routine testing isconducted for microbial contamination, as requiredby the Swiss International Office for Drug Control(723). Iscador preparations are also tested forendotoxin contamination (367). No cases of seriousinfection have been reported in the literature as aresult of subcutaneous injection of Iscador.

Indications for Use

According to current information, Iscador prepa-rations are used in several specific ways in cancertreatment. The main use of the treatment, and the onefor which Anthroposophists claim the best resultsoverall, is in the treatment of solid tumors before andafter surgery and radiotherapy. It can be given in anintensive schedule 10 to 14 days before surgery “toactivate the defensive functions, ” to “help preventmetastatic spread” due to surgery, and to promoterapid recovery. Alternatively, it can be given asfollowup treatment beginning immediately aftersurgery and continuing over several years in gradu-ally decreasing doses and increasing intervals.Either way, Iscador is claimed to significantly

l~qotiy, p=nt~ a-s~ation of Iscador cfi= a W of increased pressure in the cranial cavity due to swelling around the tumor.


improve survival rates, particularly in cancers of thecervix, ovaries, breast, stomach, colon, and lung.

A second indication claimed for Iscador is thetreatment of advanced stage, inoperable solid tu-mors. Success in such cases is said to be dependenton the general condition of the patient when thetreatment is started, but improvement in the patient’sgeneral condition, reduction of pain, cessation oftumor growth, and occasionally tumor regression areclaimed.

In addition to treating solid tumors, Iscador is alsoused for cancers of the bone marrow, connectivetissue, and blood-forming organs, specifically, lym-phomas, sarcomas, and leukemias. Proponents statethat Iscador is less effective with these cancers thanwith the solid carcinomas.

The fourth, and probably the most controversial,use of Iscador is for treatment of ‘‘precancerousstates” (847). Recent anthroposophic literaturestates that cancer can start early in life and can be in“preparation” for several years, if not decades,before a tumor develops (533,847). It is believed thata variety of factors, including psychological dam-age, unresolved problems, incidents causing shock,“strokes of fate, ” individual predispositions, andenvironmental factors, can lead to an impairedmetabolism and a gradual failure of the immunesystem, which, in turn, decrease the body’s ability toidentify and destroy malfunctioning cells (536).

Proponents cite a number of conditions, some ofwhich are associated with an increased risk ofcancer, that are treated with Iscador in an attempt toprevent their development into tumors; after treat-ment with Iscador, regression of these conditions issaid to occur, along with improvement in a patient’sgeneral condition (e.g., as shown by the “blossom-ing of patients, who for example outgrow theirrepressed and depressed frame of mind, and developnew powers and initiative again” (109)). Suchconditions are listed as the following:

●

●

●

●

Ulcerative colitis-chronic inflammatory dis-ease of the colon and rectumCervical erosion (PapanicolaouIII and IV)-dysplasia, carcinoma in situ, or invasive carci-noma of the cervixKraurosis vulvae—primary atrophy ofthe vulvaLeukoplakia-white lesions of the mucousmembranes in various organs

Proliferative mastopathy, stage III-abnormalgrowth of breast tissueCrohn’s disease-chronic inflammatory boweldiseasePapillomatosis of the bladder—abnormalgrowth of the mucosal lining of the bladderIntestinal polyposis-presence of multiplepolyps in the intestineChronic gastric ulcer-ulceration of the mu-cosa of the stomachSenile keratosis—scaly lesions of the skin(746).

In their 1984 statement on Iscador, the SwissSociety for Oncology noted that conventional surgi-cal treatment for some of these conditions, e.g.,cervical abnormalities, is likely to be simpler andeasier for patients than long-term Iscador treatmentwould be, and that Iscador treatment for theseconditions could “maintain the patient in a constantfear of cancer for many years” (847). According toinformation provided to OTA by the PhysiciansAssociation for Anthroposophical Medicine, sur-gery for these conditions is used “wherever possi-ble” (726).

Effects of Iscador Treatment

The immediate physiologic effects of Iscadorreportedly include arise in body temperature and anincrease in the number and activity of circulatingwhite blood cells. Several clinical studies of thefermented form of Iscador have noted that patientsexperience moderate fever (arise of 2.3 to 2.4 ‘C) onthe day of the injections and in some cases, also localreactions around the injection site (479), temporaryheadaches, and chills associated with the fever(367). Clinical effects of the unfermented form ofmistletoe treatment have not been reported. Iscadortreatment is also claimed to improve patients’general conditions, even after all other treatmentoptions have been exhausted (109), and to enhancehormonal and enzyme activities (specifically, byimproving thyroid and reproductive organ function),promote deeper sleep, improve appetite, relievetension and depression, increase initiative, regulatebowel movements, and increase functional capacity(534,536).

In general, proponents claim that ‘in the majorityof cases [Iscador] treatment has had positive resultssuch as improved chances of survival, enhancedquality of life, extension of life and regression of


tumours” (530). Treatment with Iscador is generallynot claimed to result in dramatic destruction oftumors. Instead, it is thought to slow the growth oftumors or even stop tumor growth altogether, andthen lead to gradual tumor regression. It is believedthat tumor cells may undergo a transformation frommalignant forms to semimalignant forms, then tochronic inflammation, and finally to normal forms(533,534).

Mode of Action

The current Anthroposophic literature describesIscador as having a unique combination of cytostatic(suppression of cell multiplication and growth) andimmune stimulating properties (533,534). Its cyto-static properties are thought to derive from itsconstituent proteins, some of which are reported toact specifically against malignant cells. One type ofprotein found in mistletoe (viscotoxin), for example,is reported to destroy cancer cell membranes in cellculture (753). Another type (lectin) is reported toinhibit the growth of proliferating cells by blockingthe synthesis of particular proteins at the ribosomallevel (301,536). Iscador’s immune stimulating prop-erties reportedly include the ability to increase thenumber and activity of certain types of immune cellsand to promote specific immune defense mecha-nisms leading to increased production of lympho-cytes (533,534).

Studies of the Biological Activity of Iscador

The scientific literature contains a number ofstudies conducted during the 1970s and 1980s on thecytostatic and immunologic properties of mistletoeextracts. It is now well-established that crudemistletoe extracts contain a cytotoxic lectin11 (695)(viscumin, also called mistletoe lectin I), severalother similar lectins, and a few cytotoxic non-lectinproteins (viscotoxins) (413,511), among other com-ponents, such aspolysaccharides (464) and alkaloids(475). The identity and characteristics of cytotoxicsubstances in the processed and fermented Iscadorpreparation, however, which differs from the crudemistletoe extract, have been less actively studied.One recent study (413) of the cytotoxic componentsof Iscador found that it does contain a substance

related to (though not the same as) mistletoe’sviscumin, along with some additional cytotoxicmaterial similar to the viscotoxins found in unfer-mented mistletoe (51 1).

Several studies have investigated the effects ofIscador, crude mistletoe extracts, and their constitu-ents on the growth of rodent and human cell lines inculture. In most cases, these substances were foundto inhibit the growth of cells in culture. The degreeof inhibition was found to vary according to thetypes of cell used, the method of preparation of theextract, the subspecies of mistletoe used, and thetype of host tree supporting the mistletoe plant(752,753).

Both crude mistletoe extracts and Iscador havebeen extensively tested for antitumor activity invarious experimental animal systems (277,475). Theresults with Iscador preparations have been mixed.Significant antitumor activity of Iscador was foundin some animal tests (Lewis lung carcinoma, colonadenocarcinoma 38, and C3H mammary adenocar-cinoma C6/C) (475). No antitumor activity wasfound in other tests (leukemia L121O (475,928),leukemia L5222 (75), leukemia P388 (928), Ehrlichascites carcinoma of the mouse (475), B16 mela-noma (475, 928), Walker 256 rat carcinoma (75),and a separate test of Lewis lung carcinoma (928)).In a test using autochthonous primary mammarycarcinomas 12 in Sprague-Dawley rats (475), nonsignifi-cant growth inhibition was observed 6 weeks afterIscador treatment, but no difference in mediansurvival time was found.

Immunologic effects of Iscador in human cells inculture and in animals have also been investigated(208,367). In cell culture, for example, it was foundthat Iscador extracts increased the activity of naturalkiller (NK) cells (374). Several studies found thatinjections of Iscador in mice resulted in enlargementof the thymus (672), and one study found increasedproduction of certain immune system cell types(745). It is not yet known which components ofIscador, e.g., the various proteins or the bacteria ora combination of several elements, are responsiblefor eliciting these reactions.

Ilbtins are biologic~y active proteins or glycoproteins that cause agglutinatio~ precipitation or other phenomena resembling an imfn~e ractionwithout stimulating an antigenic response, Lectin can bind with red blood cells of certain blood groups and with malignant cells, but not their normalcounterparts. Other Iectins stimulate the proliferation of lymphocytes.

lz~ese caminomas resemble human tumors more closely than transplanted tumors with respect to growth behavior, antigenicity, and experimentalsensitivity.


Clinical Studies With Iscador

Although Iscador treatment is given along withother interventions in Anthroposophic medicine,proponents claim that Iscador itself has anticancerproperties: it is believed to increase the length andquality of life, stabilize disease, cause regression oftumors, and improve the general condition of thepatient (534). To support these claims, proponentscite their many years of clinical experience withIscador during which individual doctor-patient en-counters convinced them of its efficacy (534). Alsocited are isolated case reports (935) of patientstreated with Iscador and various clinical studies.

The clinical studies of Iscador published up to1984, most of which are in German, were reviewedin the Swiss Society for Oncology’s paper on Iscador(847). Included among these papers were individualcase reports, retrospective clinical trials, and “con-trolled” and “uncontrolled” prospective studies.Among these, five studies described by their authorsas controlled and prospective (386,771,772,773,774)were critiqued in the Swiss paper. The Swiss Societyfor Oncology study group found that major metho-dologic flaws in each of the five studies preventedvalid conclusions about efficacy to be drawn fromthem.

Several additional clinical studies of Iscador havebeen published since the Swiss review. One recentreport described a prospective, uncontrolled study of14 patients with stage IV renal adenocarcinoma withmeasurable lung metastasis who were treated withsubcutaneous injections of Iscador (479). Treatmentwas administered every second day in escalatingdoses over 3 weeks, followed by “maintenance”treatment on alternate days. The study reported noobjective responses to Iscador treatment in thesepatients.

Other studies have examined various immuno-logic effects of Iscador treatment in patients withadvanced breast cancer (367,368,369). A number ofchanges in immunologic function interpreted by theauthors as immune enhancement were noted afterintravenous infusion of Iscador. These studies didnot examine antitumor effects or effects on survival.

PAU D’ARCOPau D’Arco is one of several commonly available

herbal products used for cancer treatment. Unlikethe proprietary Hoxsey, Essiac, and Iscador prod-

ucts, Pau D’Arco is marketed by a number ofdifferent U.S. companies through local health foodstores. It is available in the form of capsules, teabags, or loose powder. Other terms used synony-mously with Pau D’Arco include taheebo, lapacho,ipes, ipe roxo, and trumpet bush (521,861).

Pau D’Arco originates in South America, where itis said to be a popular treatment for cancer and avariety of other disorders (e.g., malaria). It isreportedly used in folk medicine for Hodgkinsdisease, leukemia, and cancers of the pancreas,esophagus, “head,” intestines, lung, and prostate(266). According to catalogs from the U.S. compa-nies that sell Pau D’Arco, the product is generallyclaimed to be a strengthening and cleansing agent,with antimicrobial properties. In the popular litera-ture, anecdotal reports of its use by U.S. cancerpatients link tumor regression with drinking PauD’Arco tea (943).

The source of Pau D’Arco is the inner bark of thepurple flowered Tabebuia impetiginosa tree inArgentina or the Tabebuia heptaphylla tree inBrazil. The method by which Pau D’Arco tea orpowder is produced is not publicly known. However,efforts to study the effects of Pau D’Arco havefocused largely on one of its chemical constituents,lapachol, a biologically active organic compound.Lapachol is said to be present, to varying degrees, incommercial preparations of Pau D’Arco, although arecent analysis found only trace amounts or nomeasurable amounts of lapachol in the bark ofspecimens of Tabebuia impetiginosa and otherspecies collected for commercial purposes (61).Less attention has been paid to the biologicalproperties of other constituents of Pau D’Arco, e.g.,several naphthoquinone compounds (340), or tocrude extracts of the whole product.

For many years it has been known that lapachol isa potent cytotoxic agent and is an active antimalarialagent in animal test systems (173). Lapachol has alsobeen extensively tested for antitumor activity in avariety of animal tumor models. It has been found tohave antitumor activity in two types of tests (Walker256 system (736,737) and Sarcoma Yoshida ascites(285)), and no significant activity in other tumormodels (Sarcoma 180 (352), L121O leukemia (700),and Adenocarcinoma 755 (173)).

A recent unpublished study described the effectsof crude extracts of Pau D’Arco, rather than lapacholalone, in mouse cells in culture and in the Lewis


Lung Carcinoma system (626). According to thatstudy, the Pau D’Arco extract stimulated the activityof macrophages derived from mice, killed LewisLung carcinoma cells in culture, and in the animalmodel, reduced the occurrence of lung metastasis inmice following surgery to remove primary tumors.The authors suggested that the Pau D’Arco extractshowed immune modulation and direct cytotoxiceffects in these experimental systems. This study hasnot yet been confirmed by other investigators.

On the basis of the positive results with lapacholin the Walker 256 animal system cited above,lapachol has been examined in at least two clinicalstudies. Following toxicologic and pharmacologicstudies of lapachol in animals (173), NCI sponsoreda phase I toxicology study of oral doses of lapacholin human subjects (81). In that study, 19 patientswith unspecified advanced non-leukemic tumorsand two patients with chronic myelocytic leukemiain relapse were given oral doses of lapachol rangingfrom 250 to 3,750 mg per day. Although the studywas designed only to measure pharmacologic andtoxic effects of the drug, it was noted that one patientwith metastatic breast cancer had a regression in oneof several bone lesions, while none of ‘he otherpatients was reported to have had objective re-sponses to the drug.

The investigators also found that high oral dosesof lapachol (1,500 mg or more per day) wereassociated with nausea, vomiting, and a prolonga-tion of prothrombin time (an indicator of bloodcoagulation processes) that returned to normal whenthe drug was withdrawn. No myelosuppression,hepatic, or renal toxicity was seen among these

patients. Based on previous animal tests, it had beendetermined that a blood level of 30 ug/ml or more oflapachol would be necessary for physiologic activityof the drug, but the toxicities observed in the clinicalstudy indicated that physiologic levels of lapachol,in the authors’ opinion, could not be reached inpatients without encountering anticoagulation reac-tions. As a result of this study, the IND for lapacholwas closed in 1970 (231) and further study oflapachol as an antitumor agent was not pursued. Ina recent paper, however, the authors noted thatlapachol’s anticoagulant effects maybe inhibited bythe coadministration of vitamin K, allowing forfuture assessment of lapachol’s antitumor effectsalone (184).

In another uncontrolled study, nine patients, all ofwhom had received previous conventional treat-ment, were given oral doses (20 to 30 mg/kg/day) oflapachol for 20 to 60 days or longer (286). Onecomplete and two partial tumor regressions werenoted in three of the nine patients: one described ashaving hepatic adenocarcinoma, another with basalcell carcinoma of the cheek with metastasis to thecervix, and a third with ulcerated squamous cellcarcinoma of the oral cavity. It was not indicatedhow the regressions were measured or their duration.Subjective improvements (e.g., reduction of pain)were noted in all nine patients. Some of the patientsreportedly showed some signs of toxicity (e.g.,nausea, dizziness, and diarrhea). Valid inferencesabout the efficacy of lapachol cannot be drawn fromthis study, since many of the clinical details are notgiven in the published report and the possible effectsof previous treatment were not accounted for.

unconventional cancer treatments (part 6 of 19)

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