Surviving Mesothelioma

According to the American Cancer Society, up to about 10 percent of people with malignant mesothelioma live at least five years after the disease is diagnosed. While that leaves miles of room for improvement, the statistic nevertheless means that a substantial fraction of patients are surviving mesothelioma—a fraction that is likely to grow with each passing year.

That’s because survival figures for mesothelioma, as well as for other cancers, are based on outcomes of patients in the past, who

received whatever treatment was available back when they first learned of their mesothelioma diagnosis. Even minor innovations in surgery or postoperative care, as well as more substantial advances in chemotherapy or other medicines, can immediately benefit

individual patients. That impact, though, can take years to begin to show up in average survival statistics. For instance, the mesothelioma treatment pemetrexed disodium (Alimta), which is given with another chemotherapy drug to patients who aren’t candidates for surgery, received U.S. government approval just seven years go, meaning that any ability to nudge up survival statistics is only beginning to appear.

In the broader war on cancer, there is even more reason for hope. In the war on cancer, many powerful weapons are in development, and in some cases, already on the battlefield. Consider a rare cancer of the white blood cells known as chronic myeloid leukemia (CML). Until the introduction of a new drug, called imatinib (Gleevec), in the United States in 2001, less than one-third of patients with CML survived for five years. The new medicine, clinical trials show, boosted that survival rate to around 90 percent or more—and is now the

standard of care for that disease.

Also, knowledge from the development of one such weapon—even if it isn’t designed to specifically attack malignant mesothelioma—can yield insights that will help in the battle against asbestos-caused disease. Every day scientists are learning more about how to attack specific tumors, how a tumor’s environment in the body can help or hinder its

growth, and what special tricks tumors use to thrive and spread. A multitude of research studies are under way to translate that knowledge into action.

Meanwhile, the medical literature on mesothelioma reflects how individual miracles happen. A report in January 2011 in the Journal of Medical Case Reports described a woman in her 40s who is alive and well seven years after diagnosis with peritoneal mesothelioma, a

cancer of the lining of the abdomen. Her physicians attribute her good fortune to the contained nature of the disease, her successful surgery and chemotherapy, and specific characteristics of her tumor tissue. Another case report, appearing just a month earlier in the journal Diagnostic Pathology, describes a patient who developed pleural mesothelioma, a cancer of the lining of the lungs, after asbestos exposure and was healthy 14 years after symptoms appeared, and a dozen years after surgery and chemotherapy. And a report from

2007, appearing in the journal The Annals of Thoracic Surgery, recounts a surgical patient whose pleural mesothelioma spontaneously regressed. The patient experienced just a single recurrence six years into a 12-year follow-up period, and that tumor in the chest was successfully removed.

In short, as oncologists and other experts will readily acknowledge, statistics reflect the history of a group—not the future of an individual.

Taking a Shot at Mesothelioma

Researchers at Memorial Sloan-Kettering Cancer Center in New York City are recruiting patients for a clinical trial to test a ―vaccine‖ under development for the mesothelioma treatment.

Unlike many well known vaccines—such as a shot to protect against onset of illnesses such as the flu or the mumps—this vaccine is intended to be given to people who already have

malignant pleural mesothelioma, a cancer of the lining of the lung. Very preliminary tests have suggested that the experimental vaccine can mobilize a patient’s own immune system to attack mesothelioma cells.

Specifically, the vaccine appears to target WT1, a type of protein that binds to a specific part of the DNA code, affecting the transfer of genetic information and impacting how cells function. WT1 is especially abundant in cells from many people’s mesothelioma tumors.

The preliminary tests, whose results were published in fall 2010 the journal Cancer Immunology, Immunotherapy, found that the vaccine worked to mobilize two different types of immune cells known as T cells, and those T cells were able to kill the cancer cells with abundant WT1. Also, the vaccine was well tolerated, causing minimal problems with

side effects among test patients, the researchers noted.

Participants in the preliminary trial, which included both malignant mesothelioma patients and those with non–small-cell lung cancer, received six doses of the vaccine, injected under the skin, along with an immune-boosting substance. Injections were given at the start of the study, and four, six, eight, 10 and 12 weeks later. People whose tumors responded received additional injections once a month.

While only a handful of patients received the vaccine in this early trial, a majority of them showed an immune response to the treatment, setting the stage for the current, Phase II randomized clinical trial. The new trial is for adult patients who have had their pleural mesothelioma tumors surgically resected and have received chemotherapy or radiation. Half

the participants will receive a series of shots over 10 weeks containing the WT1-targeted vaccine, along with some general immune-boosting medicines, while the other half will receive those general immune boosters alone. Neither the patients nor the researchers will know who received which treatment.

The research team, which hopes to enroll 78 participants whose tumors test positive for the WT1 protein, will evaluate whether or when their mesothelioma recurs for a period of one year after the vaccine treatment is completed. The principal investigator conducting the study is thoracic oncologist Dr. Lee Krug, director of the Mesothelioma Program at Memorial Sloan-Kettering. Dr. Krug can be contacted at 212-639-8420 or 646-888-4201.

The identifier number for the new mesothelioma clinical trial is NCT01265433. Researchers

expect the trial to be completed in December 2014.

Study of New Medicine for Mesothelioma Treatment

The National Cancer Institute is sponsoring a clinical trial of a new medicine in hopes that it will help mesothelioma patients whose cancers have been unresponsive to chemotherapy. The trial is being conducted at the National Institutes of Health’s Clinical Center in Bethesda, Md., and is led by Dr. Raffit Hassan.

The experimental medicine that is being tested – IMC-A12 – is a human antibody. The trial is a Phase II study, meaning the medicine has already shown promise in preclinical testing in the laboratory and has been tested in people to assess safety and proper dosage. The current research will continue to investigate safety and evaluate IMC-A12′s effectiveness against mesothelioma tumors.

The medicine, also called cixutumumab, is given intravenously in the trial once every 21 days to patients with pleural mesothelioma (cancer in the thin layer of tissue that surrounds the lungs and lines the chest cavity) or peritoneal mesothelioma (cancer in the lining of the abdomen). The study is open to adults whose tumors can’t be fully removed with surgery, and whose cancer has not responded to chemotherapy with drugs known as platinum-based agents, such as cisplatin, which is commonly used to treat mesothelioma. Patients might also be admitted if they have refused previous chemotherapy as part of their mesothelioma treatment.

Treatment will be ongoing unless patients develop severe side effects or their mesothelioma progresses. The primary goal is to see whether mesothelioma tumors partially or completely

respond to the medicine.

The antibody works somewhat in the way that glue gums up the works of a lock and prevents a key from opening a door. IMC-A12 (the ―glue‖) stops up certain receptors (―locks‖) that sit on the surface of a mesothelioma cell. That way, a protein called Type I insulin-like growth factor, or IGF-1R—the normal ―key‖ that would open the door to the cancer’s growth and survival – no longer works. This particular type of ―lock‖ and ―key‖ is also being studied in other cancers.

All participants in the IMC-A12 trial must have acceptable kidney and liver function as well as the adequate ability to form blood cells, and must not have had any major surgery, radiation treatment, chemotherapy or biologic therapy within 28 days of the start of the

new mesothelioma treatment. Potential participants will be given a complete physical exam to assess their mesothelioma and overall health.

Patients must cover their own travel expenses to be screened for possible enrollment in the trial, but those selected to participate will receive payment for out-of-town transportation costs for study treatment and follow-up. All medical care related to the trial will be provided for free at the NIH Clinical Center, but patients should maintain any current health care coverage to pay for other medical expenses.

Additional information about the mesothelioma study and its requirements can be obtained

from the cancer institute’s referral office, at 1-888-NCI-1937. The study’s identifying tag at

ClinicalTrials.gov is NCT01160458.

Mesothelioma and Gemcitabine

New research from Europe suggests that a drug known as gemcitabine, given along with one that

is now commonly used for mesothelioma, might someday serve as another weapon in doctors’

arsenals against the cancer.

Gemcitabine (marketed as Gemzar) is a chemotherapy drug currently in use to treat lung, breast,

pancreatic and ovarian cancers. In the recent, Phase II study—designed to test whether the drug

is effective and to measure side effects and other risks—investigators in Slovenia gave patients

with malignant pleural mesothelioma a prolonged, low-dose infusion of gemcitabine in

combination with cisplatin (marketed as Platinol).

The researchers decided to test this course of therapy against malignant pleural mesothelioma—a

cancer in a layer of specialized cells, called mesothelial cells, that line the chest and are adjacent

to the lungs—after noting that the treatment appeared to be effective in advanced cases of the

most common type of lung cancer, non–small-cell lung cancer.

Patients in the mesothelioma study were eligible if they had not previously received any

chemotherapy, and other than the mesothelioma, were in fair to good health with normal liver

and kidney function. The treatment entailed six three-week cycles of therapy. For the first four

cycles, patients received six-hour infusions of gemcitabine on the first and eighth days, plus

cisplatin on the second day; the last two cycles included the gemcitabine but not the cisplatin. A

total of 78 patients—58 men and 20 women, ages 33 to 82 years old—participated. More than 70

percent of the patients had mesothelioma tumors of the most common subtype, known as

epitheloid, a categorization based on certain characteristics of the cancer cells.

Four of the patients, or 5 percent, showed a complete response—meaning their cancer was

undetectable—after the therapy. Thirty-five had a partial response—meaning the size of their

tumors was reduced substantially. Another 35 patients had tumors that either responded

minimally or remained stable, while only four patients experienced tumor progression during the

treatment.

Sixty-seven percent of the mesothelioma patients survived one year after therapy; almost 33

percent survived two years, and about 20 percent survived three years. Patients who had

epitheloid tumors were more likely to survive longer without their tumor progressing, and to

survive longer overall, compared with patients who had other tumor subtypes.

Most of the patients experienced an improvement in mesothelioma symptoms, and a quality of

life that either remained the same or improved, the researchers reported. Notable side effects

included neutropenia (a shortage in a type of white blood cells, which can impair the immune

system), anemia (a shortage of red blood cells, which can cause fatigue) and hair loss, as well as

thrombocytosis (an excess of blood platelets, which cause clotting). Because the therapy

appeared to slow down the mesothelioma’s progress and didn’t prove to be too toxic, the

scientists advised that this mesothelioma treatment approach warranted further research.

Photodynamic therapy for pleural mesothelioma

A combination therapy might hold promise for extending the lives and preserving more lung function of patients with malignant pleural mesothelioma, a cancer of the lining inside the chest.

Patients in mesothelioma treatment often undergo an extensive surgery known as a modified extrapleural pneumonectomy, which involves removal of the lung and surrounding tissue and is usually accompanied by radiation of the whole chest area. But the new combination approach for mesothelioma patients adds a treatment called photodynamic therapy to a more conservative,

lung-sparing surgery called a pleurectomy.

Photodynamic therapy is a light-based treatment that is designed to eliminate any microscopic bits of residual cancer that surgeons are unable to remove. The therapy, which penetrates just a few millimeters into tissue, has three components that are administered: a nontoxic compound that sensitizes cancer cells to light; then oxygen; then specially tailored light. While the therapy is federally approved for treatment of several cancers, it remains experimental for malignant pleural mesothelioma.

Researchers at the University of Pennsylvania in Philadelphia set out to determine whether the lung-sparing surgery could be used instead of an extrapleural pneumonectomy, and whether the use of photodynamic therapy would extend patients’ survival time, compared with typical survival times in mesothelioma patients.

Nine women and 19 men with malignant pleural mesothelioma, ranging in age from 27 to 81, participated in the Phase II study from 2004 to 2008. Half received the more extensive surgery along with photodynamic therapy, while the other half had the lung-sparing surgery along with the light-based therapy.

Twelve patients in each group had stage III/IV mesothelioma—and researchers noted that many of the research subjects, due to the advanced stage of their mesothelioma or to their advanced age, would not be candidates for surgical treatment. In all, 22 patients also had chemotherapy. The two groups were comprised of mesothelioma patients with similar demographic traits such as age, sex and disease characteristics.

Among the patients who had the more extensive surgery and photodynamic therapy, the median overall survival—the point in time after treatment was completed at which half the patients were still alive—was 8.4 months. For the patients receiving the lung-sparing surgery plus the light therapy, that median point had not been reached yet, after more than two years of follow-up.

The surgeon who performed the procedures in the study, Dr. Joseph Friedberg of the Penn Mesothelioma and Pleural Program, said researchers had hoped that preservation of patients’ lungs would improve their quality of life, and that the extended survival time of those patients was a complete surprise. The scientists are continuing to investigate exactly how the photodynamic therapy might be helping to fight mesothelioma—possibly by creating a ―vaccine‖ effect with residual disease that sparks the immune system to fight any remaining cancer. Or, the photodynamic therapy might have made any residual cancer more vulnerable to other follow-up treatments.

SIDE EFFECTS OF CHEMOTHERAPY ON MESOTHELIOMA PATIENTS

While doctors might choose from an assortment of

available medicines to care for

malignant mesothelioma patients, a combination

treatment with two chemotherapy drugs—pemetrexed

disodium (marketed as Alimta) and cisplatin (marketed

as Platinol)—is a mainstay. The two drugs are typically

used in patients when surgery is not an option.

Pemetrexed received approval from the federal Food and

Drug Administration (FDA) in 2004 for the treatment of

malignant pleural mesothelioma, a cancer of the chest

cavity lining, after a randomized clinical trial showed that

the drug, given with cisplatin, extended patients’ average

survival time longer than cisplatin alone. As the first drug

shown to be effective against pleural mesothelioma,

pemetrexed received priority review from the FDA.

As with most chemotherapy treatments, mesothelioma patients are vulnerable to experiencing side

effects from the combination of pemextrexed and cisplatin. In more than half the patients in the

clinical trial, the treatment suppressed bone marrow function, which might lead to low counts of white

blood cells, the body’s infection fighters. It’s important that mesothelioma patients on pemetrexed and

cisplatin tell their doctors immediately about any signs of infection, such as fever or chills or mouth

ulcers. Vitamin B-12 and folic acid are administered with pemetrexed to reduce the risk of a low white

cell count, as well as the likelihood of other side effects.

Cisplatin and pemetrexed also lowered red blood cell counts in about one-quarter of the mesothelioma

patients in the clinical trial. This condition, known as anemia, can cause fatigue. Medicines are

available to treat both low white and low red blood cell counts. Also, research has shown that

moderate exercise can help reduce cancer patients’ fatigue, and perhaps lessen pain.

Mesothelioma patients on pemetrexed could also experience a drop in their platelet count. Platelets

help the blood to clot, and patients with reduced levels of platelets should report any signs of

bleeding. These patients also might be asked to take precautions to avoid even minor injuries that

might cause bleeding, such as using a soft toothbrush to prevent gum bleeding.

Nausea and vomiting are very common side effects of the pemetrexed-cisplatin combination;

fortunately, effective anti-nausea medicines can be prescribed. Patients should promptly tell their

doctors about those symptoms—as well as rash, diarrhea, constipation, sore or gritty eyes and other

health concerns. It’s important that mesothelioma patients keep their health care teams fully informed

of side effects and avoid choosing over-the-counter treatments without medical consultation.

To learn more about the symptoms, diagnosis, treatment options, and resources for dealing with the

lung cancer or mesothelioma, call at 1.866.855.1229 or visit www.mesotheliomanews.com .

And if you, a family member or friend have been diagnosed with mesothelioma and believe it has been caused by asbestos exposure, visit http://baronandbudd.com. Baron & Budd has been protecting the rights of people with mesothelioma for nearly 30 years. Baron & Budd can help you seek the compensation you deserve.

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