POTENTIAL PROBLEMS RELATED TO CANCER TREATMENTBy Catherine M. Handy, Ph.D., RN, AOCN

Oncology Clinical Nurse Specialist

Current Anti-Cancer Approaches

Surgery

Chemo-therapy

Radiation

Hormonaltherapy

Targetedtherapy

Remove known tumor masses

Kill rapidly dividing tumor cells, including tumor cells in adjacent tissues

Kill rapidly dividing tumor cells

Inhibit the growth and survival of hormone-dependent tumor cells

Specifically inhibit processes required for tumor cell growth

Surgery

• Surgery is the oldest and the most investigated therapy for cancer.

• Many different rationales for cancer-related surgeries– Diagnostic: To obtain tissue necessary for diagnosis and staging– Curative: To remove entire tumor with adequate margins of normal

tissue– Preventive or prophylactic: To reduce risk of cancer developing in

high-risk patients• Esophageal resection for Barrett’s esophagus• Bilateral mastectomy for BRCA mutations

– Palliative: To treat cancer symptoms, not cure• Tumor debulking• Esophageal stent placement

Radiation Therapy: Indications• Can be the primary treatment• Used before surgery to shrink tumor• Used after chemotherapy or surgery to get tumor cells left

behind• Delivered to high-risk areas to prevent cancer growth • Used to control cancer• Used to manage symptoms or to improve quality of life• Used to treat structural emergencies

Radiation Therapy Side Effects• General:

• Fatigue• Skin

• All other toxicities are particular to the organs that were in the treatment field• For example, if a patient received radiation therapy for lung cancer

the esophagus, heart, spinal cord and perhaps the thyroid also received some radiation

Chemotherapy vs. Targeted Therapies

Cytotoxic Chemotherapy

• “Poisonous substances” that interrupt normal cellular division in proliferating cells and are more effective in cancer cells due to the rapid proliferation of tumors

• Dosages generally based on BSA (Pediatric and specific agent doses may differ.)

Biotherapy/Targeted Therapies

• Designed to interfere with specific molecules or signaling pathways involved in tumor growth and progression

• Dosed in mg, units, m2

Hormone Side Effects

• Anti-estrogens• Menopause• VTE• Osteopenia/osteoporosis

• Medical castration agents• Feminization

Chemotherapy General Side Effects• Myelosuppression• GI

• Mucositis• N/V• Diarrhea

• Alopecia• Renal

Monoclonal Antibody Side Effects

• Hypersensitivity reactions: less mouse and more human = less chance of hypersensitivity

• EGFR• Skin toxicity

• VEGF• Vascular toxicity

• CD 20• lymphopenia

Kinase Inhibitor Side Effects• Because they are po, uncertain absorption• Possible interference with metabolism of other drugs and

interaction with enzymes or proteins other than designated target (e.g. cytochrome P450 enzyme)

PERIPHERAL NEUROPATHY (PN)ORCHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY (CIPN)

Definition• Often thought to refer only to numbness and tingling of

the hands or feet• PN is a group of neurologic dysfunctions that occur

outside the spine and brain.• Refers to any part of the body affected by peripheral

nerves

Incidence

In those receiving neurotoxic chemotherapeutic agents, the incidence of developing PN can range from 10% to 100%.

Risk Factors

Comorbidities:–Diabetes–Alcohol overuse–Metabolic imbalances–Vitamin B12 deficiency–Cachexia–HIV–Other paraneoplastic syndrome–Cancer–Age–Medications

Pathophysiology• CIPN is not understood totally.• Can vary depending on the type of chemotherapy given• Chemotherapy is believed to damage the sensory axons

first and then cause degeneration and dying of axons and myelin sheaths.

Pathophysiology• Axons can regenerate if the offending agent is removed.• Damage to cell bodies is often not completely reversible.

Characteristics

Sensory CIPN:– Negative manifestations such as numbness or reduced

sensation– Positive symptoms/pain sensations such as paresthesia,

dysesthesia, causalgia, and allodynia– Large sensory nerve damage may result in decreased deep

tendon reflexes and vibratory sense, ataxia, and abnormal position sense of body parts.

Characteristics

• Motor CIPN and autonomic CIPN are uncommon.• Motor CIPN is difficult to characterize as it is related to

sensory damage, such as weakness, loss of feeling, or foot pain.

• Autonomic CIPN can cause nausea, abdominal fullness or bloating, early satiety, constipation, urinary issues, and erectile dysfunction.

Associated Chemotherapy

• Vinca alkaloids, taxanes, and platinum analogs are most commonly implicated—Dose-limiting CIPN

• Less commonly, high-dose ifosfamide, high-dose methotrexate, etoposide, procarbazine, cytarabine, suramin, bortezomib, thalidomide, and arsenic trioxide

• CIPN may occur during or soon after chemotherapy administration.

• CIPN may progress with increasing doses or worsen after some drugs have been discontinued.

Assessment• Grading tools are available to grade the toxicity.• Determine the level of functional impairment.• Focus on evaluating from the patient’s perspective

(subjective data).

Assessment Tools• Semmes-Weinstein filaments for cutaneous touch• Vibration—Nerve conduction• Reflexes• Assessment of temperature• Proprioception—Romberg test for balance• Sharp/dull sensation—Pinprick test• Gait assessment—Walking on heels and toes• Muscle strength—From no contraction to active movement against full resistance

• Patient-reported symptoms

Medical Management of CIPN

• Accurate assessment is essential!• Dose adjustment of chemotherapy• Pharmacologic interventions (effectiveness not yet

established)– IV or oral calcium/magnesium– Glutathione– Supplemental vitamin E– Amifostine, glutamate, and glutamine– Xaliproden

Painful CIPN

Agents to decrease dysethetic pain:• Anticonvulsants• Tricyclic antidepressants• Opioids• Topical agents

Patient Teaching• Self-report measures• Identify triggers• Self-care measures• Online educational sites

Nursing Considerations• Complex causes with few treatments• Goals should consider quality of life.• Nurses are an integral part of the team to help manage

CIPN, especially with ongoing assessment.

HYPERGLYCEMIAMALGLYCEMIA

Diabetes Brief Overview • Characterized by high blood glucose levels• Also known as diabetes mellitus• Caused by defects in the body’s ability to produce and/or use

insulin• Hormone needed to convert glucose (sugar, starches) into

energy• Produced in the pancreas

• Glucose buildup in the blood causes diabetic complications.• Types of diabetes: type I, type II, gestational• Approximately 25.8 million people (> 8% of the population) in

the U.S. have diabetes.• Cancer survivors: 8%18% report diabetes or prediabetes.

Potential Impact• Both diabetes and cancer are prevalent diseases.

• Incidence is increasing globally for both.• Between 8%18% of patients with cancer have diabetes.• Diabetes and hypertension often coexist; if so, these two

conditions along with cancer need to be addressed when planning treatment and surveillance following treatment.

• A link exists between type II diabetes and cancer, most likely due to sharing similar risk factors.

• Drug interactions and contraindications are a possibility.• Exacerbation of symptoms related to diabetes may occur

when certain cancer treatments are administered or when cancer progresses.

Impact Examples for Patients with Diabetes• Some cancer treatment regimens include:

– Corticosteroids and other drugs, affecting blood glucose levels.

– Immunosuppressive agents, increasing the risk of poor wound healing and infection.

– Agents that result in nausea, vomiting, and diarrhea, affecting dietary intake and blood glucose levels.

– Agents causing peripheral neuropathy, increasing this complication of diabetes.

• Kidney function may also be affected by both diseases and some cancer treatments.

Nursing Care Implications• Gather thorough health history data, including detailed

information about conditions and medications. Update at each visit.

• Assess baseline and monitor blood glucose closely before, during, and following treatment for those regimens potentially affecting diabetic control.

• Assess and manage baseline and ongoing symptoms related to all conditions.

• Assist with collaboration efforts between physicians treating both diabetes and cancer.

• Promote diabetes self-management efforts; enlist assistance from a diabetes educator and dietitian to assess and plan for any needed changes in exercise, weight control, and meal planning.

Steroid Use in Cancer• Therapeutic:

• As part of Chemotherapeutic regimen for leukemia ,lymphoma, myeloma

• Treatment of Graft versus host disease (GVHD)

• Therapeutic/Prophylactic:• Prevention and treatment of chemotherapy induced nausea and

vomiting

Steroid Use in Cancer• Prophylactic:

• Prevention of hypersensitivity reactions with certain chemotherapeutic agents such as the taxanes

Steroid Induced Malglycemia• Malglycemia:

• Hypoglycemia (blood glucose < 70 mg/dl)• Hyperglycemia (blood glucose of 126 mg/dl or greater• Glycemic variability (standard deviation of two or more

measurements of 29 mg/dl or greater)

Potential Impact of Malglycemia on Clinical Outcomes In Hospitalized Patients

• Increased risk of infection and sepsis• Increased mortality• Decreased survival• Increased length of stay• Increased Toxicities

Storey, S. & Von Ah, D. (2012) Impact of malglycemia on clinical outcomes in hospitalized patients with cancer: A

review of the literature. Oncology Nursing Forum39(5), 458-465.

Strategies for Glycemic Management in the Hospitalized Patient• Diet • Physical activity• Medications

• Sulfonylureas• Metformin• Thiazolidiones• Insulin

• Basal-bolus insulin therapy

Malglycemia in the Non-Hospitalized Cancer Patient• Not as well studied• Caused by both therapeutic and prophylactic steroid use• Similar concerns with potential consequences

• Impaired cellular repair• Increased clotting• Increased aggregation of platelets• Increased inflammation• Decreased ability to fight infection• Increased cellular proliferation• Increased mortality

De Vos-Schmidt, D., & Dilworth, K. (2014). Management strategy for steroid-induced malglycemia during cancer treatment. Clinical Journal of Oncology Nursing 18(1), 41-44.

Management Strategies• Send patient to PCP or endocrinologist• One strategy developed by one oncology nurse and one

diabetes nurse educator:• All patients given corticosteroids screened with a 2 hr postprandial

blood glucose on day 2 of the first chemotherapy cycle• Blood glucose <140 mg/dl: no interventions needed• Blood glucose 140-199 mg/dl: Blood glucose meter and education

on its use and dietary carbohydrate controlDe Vos-Schmidt & Dilsworth, 2014

Management Strategies• Blood glucose > 200 mg/dl:

• Education about glucose monitoring, use of and insulin pen and dietary carbohydrate control

• Blood glucose monitoring before each meal• Dietary carbohydrate control• Sliding scale insulin

• De-Vos-Schmidt & Dilworth, 2014

HYPERTENSION

The Malignant Cell

• Overexpression of EGFR1• Cell receives continuous signals to divide.• Daughter cells do not differentiate; return to cell cycle to

divide again. • Cell makes VEGF to stimulate angiogenesis.• Cell is signaled to ignore messages for apoptosis.

Angiogenesis

• Process by which a tumor develops its own blood supply• Needed for the tumor to exceed 1 mm in diameter• Triggered by hypoxia, oncogenic signals, and pro-

angiogenic growth factors• Growth of tumor and rate of spread are related to tumor

vascularity.

Role of VEGF in Angiogenesis

• Binds to receptors on the endothelial cells of nearby blood vessels

• Sends message to increase production of more endothelial cells

• Causes endothelial cells to migrate through basement membrane and toward the tumor

• New blood vessel tube is formed.

Bevacizumab (Avastin)• Monoclonal antibody against VEGF• Activity in a variety of tumors including colorectal and

brain• Toxicity profile:

• GI perforation• Delayed would healing• Arterial and venous thrombotic events• Bleeding/hemorrhage• Hypertension

Blood Pressure Classification BP Classification SBP mmHg DBP mm Hg

Normal <120 and <80

Prehypertension 120-139 or 80-90

Stage 1 Hypertension

140-159 or 90-99

Stage 2 Hypertension

≥ 160 or ≥ 100

Management of BP for AdultsBP Classification Lifestyle

Modification

Initial Drug TherapyWithout Compelling Indication

Initial Drug Therapy With Compelling Indications

Normal Encourage

Prehypertension Yes No BP drug indicated Drug(s) for compelling indications

Stage 1 hypertension

Yes Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination

Drug(s) for compelling indications

Stage 2 hypertension

Yes Two-drug combination for most (usually thiazide-type diuretic and ACEI or ARB or BB or CCB)

Other antihypertensive drugs as needed

Hypertension Glossary• Compelling indications: other comorbid conditions that

increase risk of heart disease. Treat patients with chronic kidney disease or diabetes to BP goal of <130/80

• ACEI: Angiotension converting enzyme inhibitor• ARB: Angiotension receptor blocker• BB: Beta blocker• CCB: Calcium channel blockerNational Heart, Lung and Blood Institute: The Eighth Report of the Joint National Committee on

Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8)

Survivorship: Institute of Medicine Report

• Establish survivorship as a distinct phase of care• Implement survivorship care plans

• Build bridges between oncology and primary care• Develop and test models of care• Develop and evaluate clinical practice guidelines• Institute quality of survivorship measures• Strengthen professional education• Expand use of psychosocial and community support

services• Invest in survivorship research

Executive Summary From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, D.C.: The National Academies Press; 2006.

Cardiac

PulmonaryUrological

Renal

Liver

NeurologicalOcular

Reproductive

Organ Toxicities

Due to damaging effects of drugs or treatment on

organ-specific normal cells

Late Effects

• May appear months to years after treatment has ended

• Include physical, psychological, and cognitive effects– Bones

– Organs– Body tissues– Feelings– Moods– Actions– Post-traumatic stress disorder– Thinking

– Memory– Learning– Concentration/attention span– Math, problem solving, handwriting,

reading, and spelling– Planning and organizing– Processing

Fatigue• Affects almost 100% of patients undergoing cancer

treatments• Most common and distressing symptom of cancer patients• Related to disease, biochemical imbalance,

deconditioning, stress, treatment, quality of rest/sleep, nutrition, and functional status

• Results in altered sleep patterns, depression, anxiety, and environmental factors

• Can be lasting effect for weeks to months to years

Cardiac• Patients at risk:

• Radiation treatment in which the heart potentially received radiation:• Radiation to a mediastinal mass in lymphoma• Radiation to breast, lung, esophagus

• Early effects are pericarditis, pericardial effusion, tamponade• Late effects are valvular insufficiency, constrictive pericarditis, MILandier, W. & Smith, S. (2011). Late effects of cancer treatment. In C. H. Yarbro, D. Wujcik & B.H.

Gobel (Eds.) Cancer Nursing Principles and Practice Seventh Edition. Sudbury, MA: Jones and Bartlett Publishers

Cardiac• Chemotherapy/Targeted therapy:

• **Anthracyclines (“rubicin”)• High dose cyclophosphamide• Trastuzumab• Many agents combined with anthracyclines

• CHF and cardiomyopathy• 5-Fluoruracil and Capecitabine can cause acute coronary

symptoms• Monitor EKG, Echo, MUGALandier & Smith, 2011

Pulmonary• Radiation to the lung

• Pneumonitis• Restrictive/obstructive lung disease

• Chemotherapy• Bleomycin• Busulfan• Nitrosureas (BCNU)• Pulmonary fibrosis• Avoid high concentrations of oxygen in patients who have received

these agents• Monitor PFT, CXR

Landier & Smith, 2011

Neurological• Peripheral: Persistent peripheral neuropathy, especially

with paclitaxel• Monitor neuro exam• Neurocognitive: many after chemotherapy complain of

“chemo brain” and exhibit neurocognitive testing• Monitor neurocognitive testing

Landier & Smith , 2011

Neurological• Central Nervous System:

• Neurosurgery• High doses of radiation to brain

• Can have motor and sensory deficits, seizures, CVA, leukoencephalopathy

• Auditory: hearing loss with platinum chemotherapy• Ocular: cataracts and glaucoma with corticosteroids• Monitor neuro, audiological and visual exam; imaging as

indicatedLandrier & Story , 2011

Reproductive• In general the alkylating agents can cause infertility in

men and women• In men, prostate cancer therapy (radiation or surgery) can

cause impotence and incontinence• Androgen deprivation therapy (medical castration) can

cause hypogonadism• Monitor FSH, testosteroneLandier & Story, 2011

Reproductive• In women, pelvic irradiation may cause vaginal stenosis,

uterine vascular insufficiency• Hormone therapy with tamoxifen, aromatase inhibitors,

lupron may cause early menopause• Monitor FSH, LH, estradiol

Landrier & Story, 2011

Gastrointestinal• With surgery or radiation may see adhesions, strictures,

perforations, impaired absorption of nutrients, diarrhea, fecal incontinence, chronic enterocolitis, anorexia

• May see impaired swallowing after head and neck irradiation

• Monitor electrolytes, colonoscopyLandrier & Story , 2011

Liver• Treatment with antimetabolites or abdominal radiation

can lead to hepatic dysfunction• Monitor LFTs, imaging as indicated

Landrier & Story, 2011

GU• After bladder, prostate or spinal surgery may see

incontinence, dysfunctional voiding, neurogenic bladder• Hemorrhagic cystitis after cyclopohosphamide• Monitor UA

Landrier & Story , 2011

Renal• Chemotherapy:

• Platinum agents• Ifosfamide• Methotrexate• Nitrosureas

• Symptoms:• Glomerular toxicity• Tubular dysfunction• Renal insufficiency• Chronic kidney disease

• Monitor renal function tests, UALandrier & Story ,2011

Lymphatic• Radiation to the lymph node channel or lymph node

dissections can result in lymphedema

Landrier & Story ,2011

Musculoskeletal• Treatment with corticosteroids, androgen deprivation

therapy, aromatase inhibitors, surgical castration, oopherectomy may result in osteopenia/osteonecrosis

Landrier & Story , 2011

Dental• Xerostomia, dental caries and periodontal disease with

radiation• Osteonecrosis with bisphosphonate therapy• Dental care as indicated

Landrier & Story, 2011

Hematologic• Alkylating agents and other chemotheraeutic agents can

cause myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML)

• Monitor CBC

Landrier & Story ,2011

Chronic Graft-Versus-Host Disease• Occurs 324 months after transplant• May involve skin, liver, eyes, mouth, upper respiratory

tract, and esophagus• Erythematous skin rash is hallmark manifestation. • Cyclosporine and corticosteroids

Psychosocial• Depression• Anxiety• PTSD• Limitations in health care access• Alterations in body image• Psychosocial assessment

Landrier & Story ,2011

Institute of Medicine Report

• Establish survivorship as a distinct phase of care• Implement survivorship care plans

• Build bridges between oncology and primary care• Develop and test models of care• Develop and evaluate clinical practice guidelines• Institute quality of survivorship measures• Strengthen professional education• Expand use of psychosocial and community support

services• Invest in survivorship research

Executive Summary From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, D.C.: The National Academies Press; 2006.

ReferencesAmerican Diabetes Association. (2014). Diabetes basics. Retrieved from

http://www.diabetes.org/diabetes-basics Edgington, A., & Morgan, M.A. (2010). Looking beyond recurrence: Comorbidities in

cancer survivorship. Clinical Journal of Oncology Nursing, 15, E3E12.Giovannucci, E., Harlan, D.M., Archer, M.C., Bergenstal, R.M., Gapstur, S.M.,

Habel, L.A., . . . Yee, D. (2010). Diabetes and cancer: Consensus report. Diabetes Care, 33, 16741685. Retrieved from http://care.diabetesjournals.org/content/33/7/1674.long

U.S. National Library of Medicine, MedlinePlus. (2014). Diabetes. Retrieved from http://www.nlm.nih.gov/medlineplus/diabetes.html

U.S. National Library of Medicine, PubMed Health: A.D.A.M. Medical Encyclopedia. (2014). Diabetes. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002194

Stevens, C., Dinkel, S., & Catanzaro, J. (2011). The complex dual diagnosis of diabetes and cancer. Clinical Journal of Oncology Nursing, 15(6), 654-658.

ReferencesBiedrzycki, B.A. (2010). Peripheral neuropathy. In C.G. Brown (Ed.), A

guide to oncology symptom management (pp. 405421). Pittsburgh, PA: Oncology Nursing Society.

De Vos-Schmidt, D. & Dilsworth, K. (2014). Management strategy for steroid-induced malglycemia during cancer treatment. Clinical Journal of Oncology Nursing, 18,41-44.

Landrier, W. & Smith, S. (2011). Late effects of cancer treatment. In C.H. Yarbro, D. Wujcik & B.H. Gobel (Eds.), Cancer Nursing: Principles and Practice (pp. 1755-1779). Sudbury, MA: Jones and Bartlett Publishers.

National Heart, Lung, and Blood Institute (2014). The Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8).

Oncology Nursing Society. (2009). Putting evidence into practice: Peripheral neuropathy. Retrieved from http://www.ons.org/Research/PEP/Peripheral

Storey, S. & Von Ah, D. (2012). Impact of malglycemia on clinical outcomes in hospitalized patients with cancer: A review of the literature. Oncology Nursing Forum, 39 (5), 458-465.

Wickham, R. (2007). Chemotherapy-induced peripheral neuropathy: A review and implications for oncology nursing practice. Clinical Journal of Oncology Nursing, 11, 361376.

References

American Cancer Society. (2012). Cancer facts and figures. Retrieved from http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/index

Eggert, J. (2010). Cancer biology. In J. Eggert (Ed.), Cancer basics. Pittsburgh, PA: Oncology Nursing Society.

Van Gerpen, R. (2007). Pathophysiology. In M.E. Langhorne, J.S. Fulton, & S.E. Otto (Eds.), Oncology nursing (5th ed., pp. 298308). St. Louis, MO: Mosby.