Chapter

Chemotherapy for Non-smal Cel Lung Cancer
Marianne J. Davies, DNP, CNS-BC, ACNP-BC, AOCNP-BC and
Amanda E. Reid, MSN, APRN, ANP-BC

Introduction
There are several treatment strategies available for non-small cell lung cancer (NSCLC). These
include surgery, radiation therapy, chemotherapy, targeted therapy, immunotherapy, and palliative care. Patients may be treated with one type of treatment or a combination of treatments. This chapter reviews the use of chemotherapy and targeted therapies in the treatment of NSCLC. Chemotherapy is a form of treatment that is distributed throughout the body to kill cancer cells. Chemotherapy kills not only the rapidly dividing cancer cells but also some rapidly dividing normal cells in the body. It is usually given intravenously. Some of the normal cells that can be affected by chemotherapy include cells in the gastrointestinal tract, bone marrow, and hair follicles. This effect on normal tissue results in side effects. Chemotherapy agents that are selected to treat NSCLC have been approved for use after extensive clinical research. Some of these chemotherapy agents have been approved in combination with each other. Chemotherapy agents are identified by the generic name and brand names, and either name is used when treatment is explained to patients (Appendix 1). Targeted therapies are agents that target unique abnormalities found in specific tumors. These therapies function by inhibiting the blood supply to tumors and inhibiting growth factors needed for tumor growth. Cancerous tumors require blood supply for nutrition and to survive. This process is referred to as angiogenesis. Some targeted therapies, such as monoclonal antibodies, prevent tumor cells from developing blood vessels therefore blocking nutrition, leading to tumor death. These agents are referred to as anti-angiogenic agents. The most common anti-angiogenic agents block the vascular endothelial growth factor (VEGF). Other targeted therapies, called small molecules, block growth factors or "driver-mutations" that are needed for tumors to grow and spread. It is necessary to identify if tumor cell growth relies on a "driver-mutation" to survive. The most common driver mutation targets in lung cancer are epidermal growth factor receptor (EGFR), EML4-ALK, and HER2.1, 2 Targeted therapies may be administered intravenously or taken orally. Targeted therapies may be referred to by their generic or brand names (Appendix 2). Caring Ambassadors Program 2014 Caring Ambassadors Lung Cancer Choices, 2nd Edition Treatment of lung cancer requires a multidisciplinary Treatment Team approach. Several healthcare professionals are involved in patient care, and each has expertise in the treatment of lung cancer. It is valuable to seek treatment at a facility that has a lung cancer specialty program and a treatment team with which the patient is comfortable. Medical Oncologist
Following a diagnosis of NSCLC, the patient is referred to a medical oncologist, a physician
who specializes in the medical management of cancer. In cancer centers, hospitals, or large clinics, the physicians may specialize in one type of cancer. In smaller community practices, the oncologist may treat patients with a variety of cancers. It is important for the patient to see an oncologist who has a special interest in treating lung cancer. The medical oncologist reviews the medical history, pathology, and diagnostic tests, and performs a physical examination. Treatment recommendations are based on the stage of the disease, physical condition, functional status and history of previous treatment for cancer. Functional or Performance status is assessed by the ability of the patient to carry out their normal daily activities (Table 1). The medical oncologist prescribes and monitors response to treatment and performs follow- up evaluations. The decision to administer chemotherapy does not depend on a patient's age, and many studies have shown that elderly patients can successfully receive chemotherapy.3 However, treatment of lung cancer varies from one person to another, and the type of chemotherapy prescribed may depend on the specifics of the patient's disease. Table 1. Eastern Cooperative Oncology Group (ECOG) Performance Status Fully active, able to carry out all daily activities Decreased activity, but able to walk and carry out light activities (light house work or office work) Able to walk and care for self, but unable to carry out any work activities. Up and active > 50% waking hours Able to do only minimal self-care; confined to bed or chair > 50% waking Completely disabled. Cannot carry out any self-care. Totally confined to Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer Advanced Practice Provider (Nurse Practitioner or Physician Assistant)
The oncology advanced practice provider is an integral member of the treatment team. An
advanced practice nurse has received additional master's level education and certification beyond nursing school. Physician Assistants complete a master's level education beyond undergraduate education. The advanced practice provider is involved in the overall coordination of the cancer care, performs physical examinations, and may diagnose and treat health problems related to cancer and cancer treatment. The advanced practice provider may order diagnostic tests, perform certain procedures, and prescribe medications and other treatments.
Oncology Nurse
The oncology nurse works closely with the physician and advanced practice provider to
provide optimal care to the patient and family. This nurse has special training and certification in administering chemotherapy and managing side effects. The oncology nurse may start the intravenous line, administer the chemotherapy, and monitor for symptoms during and after the infusion. This nurse also reinforces education about managing side effects and coordinates additional nursing services needed in the home.
Social Worker
A licensed clinical oncology social worker specializes in assessing psychological, social, and
emotional concerns, counseling support for cancer patients and families, and assisting with referrals to hospital and community resources. The oncology social worker may collaborate with the interdisciplinary team about care plans at different stages of illness. Many oncology social workers facilitate support groups for patients and families and may offer groups that address the needs of specific cancer patients such as those with lung cancer. The patient may find out about available social work services by asking their care providers, local hospital, or cancer organizations such as the American Cancer Society.
Pharmacist
A licensed pharmacist who specializes in oncology may be part of your treatment team if the
patient is being treated at a large oncology practice, designated cancer center or hospital. The pharmacist will review your treatment regimen, medications and prepare your chemotherapy infusion. They are available to help council you about how to take your medications/chemotherapy, what the expected side effects are, and how to self-manage common side effects as well as educate you when to seek medical care.
Nutritionist
A licensed nutritionist specializes in assessing nutritional needs during treatment. This
healthcare specialist may assist the patient and family monitor dietary intake and may provide suggestions to improve nutrition during and after treatment.
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Caring Ambassadors Lung Cancer Choices, 2nd Edition Chemotherapy for Lung Cancer
The purpose of chemotherapy treatment may vary, Goals of Treatment depending on the patient's situation. Treatment goals may include curing the cancer, keeping the cancer under control and preventing it from spreading (metastasizing) to other areas of the body, decreasing tumor size to minimize pain and other negative symptoms (palliative), and treating recurrent disease. Chemotherapy may be administered at different times and in different sequences during the disease course. Neoadjuvant chemotherapy, given before surgery, may decrease tumor size, so surgery is more effective. Adjuvant chemotherapy is given after surgery to kill tumor cells that might be remaining in the body. Concurrent chemotherapy is chemotherapy given with radiation therapy. This may be done before or after surgical resection (tri-modality treatment). Chemotherapy can also be given along without regards to surgery or radiation therapy. Chemotherapy and some targeted therapies may be Administration of Chemotherapy given in an infusion center clinic, a physician's office, or a hospital. The safest location for receiving treatment may depend on the type of chemotherapy and duration of infusion. Chemotherapy agents may be used alone or in combination with other agents, and treatment is given on a schedule, in blocks of time known as cycles. The specific cycles vary depending on the treatment combination. Each chemotherapy cycle usually is followed by a recovery period to allow the normal cells to repair. However, the chemotherapy schedule may be changed when the patient experiences severe side effects from treatment. Chemotherapy is given intravenously via the bloodstream throughout the entire body. Techniques for intravenous chemotherapy include:  Peripheral intravenous: A catheter or needle is inserted into an arm vein on the day of the chemotherapy infusion, and is removed at the end of treatment.  Infusion port: This is a more permanent device that is placed under the skin, includes a catheter that tunnels into a larger vein, and remains in place throughout the treatment course. A specially trained chemotherapy nurse places a needle into the port through the skin to administer chemotherapy, give hydration, and draw blood samples. Only specially trained nurses or providers can access the port. When the needle is not in place, the patient may participate in normal activities, including showering.  Peripherally inserted central catheter (PICC): This is a catheter placed through a large vein in the arm, neck, or chest for chemotherapy, hydration, or drawing blood. The catheter extends outside the body, and only specially trained chemotherapy nurses access this catheter. This catheter requires a bandage dressing over the exit site to prevent infections. The catheter must be protected from getting wet. The chemotherapy nurse educates patients in how to care for the catheter and dressing at home. Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer  Pump: Some chemotherapy treatments require a continuous infusion for several hours or days. An infusion pump ensures that the accurate about of chemotherapy is infused into the body at a specific rate. Some chemotherapy drugs are given as an injection into the skin or muscle, and some are taken by mouth. Targeted therapies are usually taken by mouth in pill form on a daily basis. Targeted therapies that are taken orally usually have to be ordered through a specialty pharmacy. The processing of the prescription may take several days. In many cases, the prescription will be delivered to the patient via US postal mail. It is important for the patient to notify their healthcare team if there is delay in obtaining the prescription. Once the patient receives the prescription for the targeted oral therapy, health care provider may want to review with the patient specific instructions for taking the therapy. Often targeted therapies need to be taken hours after or before meals and other medications. Evaluation before the start of chemotherapy includes a physical examination to assess performance status (Table 1) and pulmonary, cardiac, and neurologic function. Blood tests, diagnostic tests, and other procedures are necessary. Blood tests are obtained on a regular schedule to evaluate for side effects of treatment. The complete blood count assesses white blood cells, red blood cells (hemoglobin or hematocrit), and platelets. Complete metabolic chemistry panel includes assessment of electrolytes (potassium, calcium, sodium, chloride, and magnesium), kidney function, and liver function. Prior to starting treatment, prescriptions are provided for supportive care medications that may be required during chemotherapy. Supportive care medications are those that treat the side effects of your cancer treatment. It is important to have the prescriptions filled before treatment and tell the healthcare team about any difficulties obtaining or starting the medications as prescribed. Smoking should be stopped before chemotherapy, and many centers offer smoking cessation counseling. Exercise is important to maintain energy, and it is important to have a balance between maintaining physical activity and getting adequate rest. A normal, balanced diet is recommended during treatment. It is important that the patient informs the healthcare team about all medications, including non-prescription ("over the counter") medication, because some medications may interfere with the chemotherapy, making treatment less effective or side effects more severe. On the day of treatment, the patient is evaluated by Treatment Procedure the physician or advanced practice provider to evaluate and address any changes in how the patient is feeling. The height and weight are measured because these measurements are used to calculate the dose of chemotherapy. The oncology nurse will insert the intravenous line or access the infusion port. Intravenous fluids (hydration) may be given before the chemotherapy. Other medications are given to help prevent side effects of treatment such as nausea or allergic reaction. The nurse administers the chemotherapy through the intravenous line, either by syringe or pump infusion. During and after treatment, the patient is monitored closely and notifies the nurse about any unusual symptoms or side effects. Information is
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Caring Ambassadors Lung Cancer Choices, 2nd Edition given to the patient about the chemotherapy and possible side effects, and a schedule for future appointments is provided. During and after chemotherapy, the patient is routinely evaluated, for potential side effects, with a physical examination and blood tests. The healthcare team asks the patient about any possible side effects, symptoms of disease, and strategies they have used for symptom management. The patient is encouraged to contact the healthcare team for any unusual side effects or new symptoms that occur post chemotherapy infusion. The oncologist performs tests intermittently throughout the treatment course to assess the effectiveness of treatment. This evaluation may include a computerized tomography (CT) scan, magnetic resonance imaging (MRI) scan, or positron emission tomography (PET) scan. The MRI and CT scans provide a 3-dimensional view of the organs examined, and the PET scan may distinguish normal cells from tumor cells that are rapidly dividing. The diagnostic tests may be compared with tests from the time of diagnosis. The radiologist and oncologist review the imaging tests to measure the tumor response to treatment. If the cancer has been surgically removed, the patient might receive a prescribed number of cycles of chemotherapy with or without radiation therapy. After completing this regimen, repeat (restaging) scans are performed. However, if chemotherapy is the primary treatment modality, restaging scans are usually done after every two to three cycles of chemotherapy.

Chemotherapy for Different Cancer Stages
Stage I NSCLC is a smal tumor with no lymph node involvement. Stage II NSCLC is a smal or larger tumor Early Stage Lung Cancer with lymph node involvement confined to one lung. (Stage I and II) The initial treatment of choice for stage I and II NSCLC is surgery, but chemotherapy may be incorporated into the treatment plan as wel .4-12 Radiation therapy, including stereotactic radiosurgery may be necessary if the primary tumor is not able to be surgical y removed.4 Stage I NSCLC may recur at local (regional) or distant (metastatic) sites. If the disease recurs at the same site, the area may be treated with local radiation therapy. Patients may be asked to participate in clinical trials to investigate adjuvant (postoperative) chemotherapy. For stage II NSCLC, chemotherapy and surgery are effective treatments and improve patient survival. Chemotherapy may be used before surgery (neoadjuvant) or after surgery (adjuvant). Neoadjuvant chemotherapy may decrease the tumor size so surgery may be less extensive. Chemotherapy also may treat cancer cel s that may have traveled to other parts of the body (micrometastasis) but cannot be identified with current diagnostic scans. Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer Stage III A NSCLC is a large tumor with invasion or lymph node involvement in the central chest region Stage IIIA Lung Cancer (mediastinum). Most cases of stage IIIA NSCLC are not surgically resectable because of the large extent of disease. Stage IIIA NSCLC often receives combination treatment, with four to six cycles of chemotherapy, in one of the following schedules: 4, 9-16 (Table 2,3,4)  Neoadjuvant chemotherapy: This is chemotherapy before surgery.  Induction chemotherapy before concurrent chemotherapy: This is chemotherapy alone before a course of chemotherapy and radiation therapy.  Neoadjuvant chemotherapy with concurrent radiation: Chemotherapy and radiation therapy may be given together before surgery.  Neoadjuvant therapy with sequential radiation: If the combination of both chemotherapy and radiation may not be tolerated, the patient may be given the combination of treatments in a sequence, one treatment after completion of the other. Table 2. Adjuvant Chemotherapy for Stage IIIA Non-small Cell Lung Cancer Chemotherapy Regimen
Schedule
Cisplatin, day 1 and 8 Every 28 days x 4 cycles Vinorelbine days 1, 8, 15, 22 Cisplatin, day 1 Every 28 days x 4 cycles Vinorelbine, days 1, 8, 15, 22 Cisplatin, day 1 Every 21 days x 4 cycles Vinorelbine, days 1 and 8 Cisplatin, day 1 Every 28 days x 4 cycles Etoposide, days 1 to 3 Cisplatin, day 1 Every 21 days x 4 cycles Gemcitabine, days 1 and 8 Cisplatin, day 1 Every 21 days (x 2-4 cycles) Docetaxel, day 1 Cisplatin, day 1 Every 21 days (x 2-4 cycles) Pemetrexed, day 1 Carboplatin, day 1 Every 21 days (x 2-4 cycles) Paclitaxel, day 1
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Caring Ambassadors Lung Cancer Choices, 2nd Edition Table 3. Concurrent Chemotherapy with Radiation Therapy for Stage IIIA Non-small Cell Lung Cancer Radiation Therapy (Concurrent with
Cisplatin, days 1,8, 29, and 36 Total dose, 61 cGy Etoposide, days 1 through 5 and Typically 6 weeks, daily (Monday through Friday) days 29 through 33 Carboplatin, day 1 Typically 7 weeks Pemetrexed, day 1 Every 21 days, x 4 cycles (non-squamous) Cisplatin, day 1 Typically 7 weeks Pemetrexed, day 1 Every 21 days, x 3 cycles (non-squamous) Cisplatin, days 1 and 29 Typically 6 weeks, daily (Monday through Friday) Vinblastine, weekly x 6 Table 4. Sequential Chemotherapy with Radiation Therapy for Stage IIIA Non-small Cell Lung Cancer Radiation Therapy
(After Chemotherapy)
Carboplatin, every 3 weeks x 2 cycles Paclitaxel, every 3 weeks x 2 cycles Cisplatin, days 1 and 29 Vinblastine, weekly on days 1, 8, 15, 22, 29 Stage IIIB NSCLC is unresectable disease with local involvement. Stage IV NSCLC includes extensive Advanced Stage Lung Cancer local spread or metastasis of the cancer to other (Stages IIIB and IV) regions in the body such as the brain, liver, or adrenal glands or the development a malignant pleural or pericardial effusion. The treatment goals for advanced stage disease include prolonging survival and controlling symptoms.17-19 Supportive care includes treatment that controls symptoms, but may not necessarily treat the cancer directly. Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer Treatment for advanced stage lung cancer, with no known driver mutation, usually consists of combination treatment that includes a platinum chemotherapy agent. If the patient has a poor performance status, a single agent may be used. Patients with non-small cell lung cancer, who are being considered to receive systemic chemotherapy, should be assessed with a genetic test on their tumor biopsy for a mutation of the epidermal growth factor receptor (EGFR) and EML4-ALK. Patients who have the EGFR mutation may receive oral treatment with erlotinib or afatinib.40 Either erlotinib or afatinib may be selected as first line treatment. If patients develop a resistance to the first therapy, the second EGFR agent may be started. Patients with an EML4-ALK mutation may receive oral treatment with crizotinib.39 If there is progression of disease or resistance to therapy ceritinib may be utilized.41 There is much research on additional tumor driver mutations including KRAS, ROS and BRAF. In the future, there are likely to be additional targets and targeted therapies for patients with lung cancer. Patients who do not have the EGFR or EML-4/ALK, mutation may be treated with combination chemotherapy if they are in healthy condition or a single agent if they have poor performance status. Selection of chemotherapy also is based on the specific type of NSCLC. Treatment usually is given for four to six cycles if there is tumor response or stable disease. It is standard for two chemotherapy drugs to be used together (doublet). Treatment options for different types of NSCLC include 4: Non-squamous cel NSCLC: 1. Cisplatin/Carboplatin-based doublet with or without bevacizumab 2. Cisplatin/Carboplatin-based doublet and cetuximab 3. Cisplatin/Carboplatin and pemetrexed 4. Vinerelbine and cetuximab Squamous cel NSCLC 1. Cisplatin/Carboplatin and gemcitabine 2. Carboplatin and Abraxane 3. Vinerelbine and cetuximab Maintenance therapy consists of ongoing administration (beyond four to six cycles) of at least Maintenance Therapy for Advanced one chemotherapy or targeted agent given during primary treatment. The goal is to extend long-term benefit from primary treatment. Examples of maintenance therapy include:  Bevacizumab, continued after four to six cycles of cisplatin/carboplatin-doublet and  Cetuximab, continued after four to six cycles of cisplatin/carboplatin-doublet and cetuximab
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Caring Ambassadors Lung Cancer Choices, 2nd Edition  Pemetrexed: continued after four to six cycles of cisplatin/carboplatin and pemetrexed for patients with non-squamous cell NSCLC.  Bevacizumab & Pemetrexed after four to six cycles of cisplatin/carboplatin, pemetrexed & Switch maintenance is the initiation of a new chemotherapy agent after primary treatment is completed. Examples of switch maintenance therapy include:  Pemetrexed after four to six cycles of cisplatin/carboplatin-doublet for patients with non- squamous cell NSCLC.  Docetaxel after four to six cycles of cisplatin/carboplatin-doublet in patients with squamous Clinical trials are supervised research studies that investigate the effectiveness and safety of new cancer treatments or the combination of new treatments with established treatments. The trials are designed to compare new treatment strategies with the current standard of care and to improve survival outcomes. (See Chapter 6: Clinical Trials and Emerging Therapies for Lung Cancer) Second line treatment is treatment for disease progression or recurrence. The physician does a Recurrent Non-smal Cel Lung Cancer complete review of the disease, treatment history, and reviews new and previous diagnostic scans. It is important for the physician to understand how well the patient tolerated the first line of treatment and if there are any residual side effects. Frequently, a different combination of chemotherapy drugs is used if the disease recurs soon after completing the first line of treatment. Radiation therapy and surgery may be considered depending on the site of recurrence. Targeted agents such as erlotinib, afatinib, crizotinib and ceritinib may be continued in the setting of Continuation After Disease Progression disease progression in patients with EGFR and ALK mutations. The chemotherapy portion of the regimen is discontinued.
Chemotherapy Side Effects
Chemotherapy for NSCLC can cause many unwanted side effects. These side effects occur because
chemotherapy drugs kill both cancer cells and rapidly dividing normal cells. Healthy cells that may be affected include bone marrow, blood, intestinal, oral, and hair cells. Not every side effect of chemotherapy may be experienced. Frequency and severity of side effects may depend on factors such as the dosage, route (intravenous or oral), frequency (how often chemotherapy is given), and response of the individual body to the chemotherapy. The patient should speak with the oncology team about specific side effects that may be expected and about how to prevent and treat them. Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer Side effects of chemotherapy include and are not limited to anemia, leukopenia, thrombocytopenia, nausea, vomiting, diarrhea, constipation, mucositis, peripheral neuropathy, alopecia, infection, pain, and fatigue. The patient may also experience changes in appetite, skin, nails, vision, hearing, or cognition. The patient may have flu-like symptoms, including body and muscle aches, fever, chills, headache, and nasal congestion. Bone marrow is a thick, pasty liquid inside bones where new red blood cells, white blood cells, and Bone Marrow Suppression platelets are formed. When bone marrow suppression occurs from chemotherapy, production of these cells is decreased. Bone marrow suppression is diagnosed with a complete blood count, a blood test that measures the number of red blood cells, white blood cells, and platelets. Bone marrow suppression may include anemia (a decrease in red blood cells), leukopenia (a decrease in white blood cells), and thrombocytopenia (a decrease in platelets), and is more likely to occur with more cycles of chemotherapy. Chemotherapy induced anemia is caused by the impairment of the cellular products needed to make red blood cells in the bone marrow as well as a decrease in the production of erythropoietin, a substance produced by the kidney. 20 The platinum chemotherapy agents such as Cisplatin and Carboplatin are well known to cause anemia. Signs and symptoms of anemia include weakness, fatigue, dizziness, lightheadedness, shortness of breath, and pallor of the fingernails, palms of the hands, eyelids, and inside of the mouth. Anemia may be prevented by eating a diet rich in iron and folate, including red meats and green leafy vegetables, drinking plenty of fluids, and doing mild exercise daily such as walking for 15 to 30 minutes. Medical evaluation is advised for symptoms of increased fatigue, inability to do normal activities, shortness of breath, chest pain, bleeding, or inability to think clearly. Treatment for anemia may include a blood transfusion or drugs such as epoetin alfa or darbepoetin alfa, however these drugs are not indicated for all cancer patients and have risk for developing blood clots, high blood pressure, and seizures. 20 When leukopenia (decrease in the white blood cell count) occurs the body is prone to infections. There are many different types of white blood cells. The neutrophils make up most of the white blood cell count. Usually, the white blood cell count is lowest 10 to 14 days after chemotherapy. A decrease in the number of neutrophils (neutropenia) occurs during this time. It is extremely important to take measures to prevent infection during chemotherapy by washing the hands frequently, avoiding large crowds, limiting time spent with small children as they carry a lot of germs and avoiding sick individuals. Most infections arise from bacteria from the patient's own mouth, airway, skin, urinary tract, or rectum. It is important for the patient to bathe daily and perform oral care 3-4 times a day as well as good perineal care. The patient should contact their healthcare provider immediately if they develop a high fever (temperature equal to or greater than 100.4○F), chills, new onset of cough or shortness of breath, burning with urination, vaginal discharge, or pain, swelling, redness, or warmth at an intravenous site or any site of injury. Severe untreated neutropenia is very dangerous. Patients should be treated with antibiotics immediately.21 If the white blood cell count is expected to decrease, treatment with growth factors such as filgrastim or pegfilgrastim within 24 to 48 hours after chemotherapy may decrease the length of leukopenia and thus decreasing the risk of developing infections.
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Caring Ambassadors Lung Cancer Choices, 2nd Edition Platelets help the blood form clots in response to injury. With thrombocytopenia (low platelet count), blood clot formation is impaired. Signs include easy bleeding or bruising, purple or red spots (petechiae) on the skin, blood in the urine, bloody or black stools, and extreme weakness. Treatment may include a platelet transfusion or administration of growth factors. Patients should use a soft bristle toothbrush, only use electric razors, and protect themselves from injury. The most common side effect of chemotherapy is nausea and vomiting. Nausea and vomiting are Nausea and Vomiting caused by different impulses received from the digestive track and the brain. Anti-nausea medications block different pathways and neurotransmitter receptors. 22-24 Several antiemetic drugs are available and work differently to prevent and treat different types of nausea, including acute, delayed, anticipatory, breakthrough, or refractory nausea (Table 5). Different antiemetic drugs commonly are used in combination and may be given before, during, or after chemotherapy. When the optimal antiemetic regimen is used, nausea or vomiting may be prevented. Nausea and vomiting also may be managed by decreasing unnecessary motion, eating slowly, eating small frequent meals and avoiding large meals, and sipping on water, ginger ale, or electrolyte-rich fluids. Behavioral therapies useful for nausea induced by chemotherapy include acupuncture, acupressure, guided imagery, and relaxation methods. The patient should contact their provider if they experience uncontrollable or ongoing nausea, projectile vomiting, severe stomach pain or bloating, weight loss, or vomit that is bloody or appears like coffee grounds. Risk factors for developing nausea and vomiting including the female gender, history of prior chemotherapy induced nausea and vomiting, younger than 50 years of age, dehydration, electrolyte imbalances, past history of motion sickness, brain metastases, anxiety, bowel obstruction or slow bowl transit, and use of opioids to control pain. 25
Table 5. Common Antiemetic Drugs for Nausea and Vomiting Induced by Chemotherapy
22-24
Dexamethasone (Decadron®) Ondansetron (Zofran®) Dolasetron (Anzemet®) Granisetron (Granisol®, Kytril®, Sancuso®) Palonosetron (Aloxi®) Aprepitant or Fosaprepitant (Emend®) Prochlorperazine (Compazine®) Promethazine (Phenergan®) Metoclopramide (Reglan®) Haloperidol (Haldol®) Lorazepam (Ativan®) Alprazaolam (Xanax®) Scopolamine Transdermal Patch Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer Diarrhea is defined as two to three loose or watery bowel movements daily. When the intestines are not working properly, the fluid remains in the stool and causes loose or watery bowel movements. If untreated, diarrhea can cause dehydration and loss of important electrolytes that are needed for normal function. Diarrhea can cause dizziness, weakness, fatigue, weight loss, nausea, abdominal pain, abdominal cramping, or bloating. The primary treatment for diarrhea is fluid replacement and stool bulking. This can be done by drinking electrolyte-rich fluids such as water, juice, soup broth, or commercially available electrolyte drinks and consuming bulking foods such as bananas, rice, apple sauce, oat cereal, toast, crackers, or potatoes. Patients with diarrhea should avoid consuming caffeinated beverages, alcohol, milk products, and high fiber, high fatty, spicy, and gas producing foods such as beans, nuts, raw vegetables, corn, dried fruits, or hot peppers. Many nonprescription products can help stop diarrhea, including loperamide (Imodium®) or bismuth subsalicylate (Pepto-Bismol®). However, sometimes diarrhea can be so severe that prescription medications are prescribed such as diphenoxylate and atropine (Lomotil®). The patient should keep a record of the number of loose stools per day and clean the area around the rectum thoroughly. The patient's provider should be notified immediately for diarrhea that does not resolve and is associated with fever, inability to eat or drink, decreased urination, or bloody or black stools. Constipation occurs when bowel movements are infrequent (no bowel movement in 3 days) or stool is Constipation difficult to pass. Cancer-related constipation is mainly caused by chemotherapy and medications to treat cancer pain. Prevention of constipation includes eating a diet high in fiber (grains, beans, and vegetables), drinking 8 glasses of fluids daily, walking or exercising regularly, and establishing a bathroom routine. Medications to treat and prevent constipation include stool softeners and laxatives. The provider should be contacted if a patient develops constipation that is associated with abdominal pain, vomiting, or inability to eat, hard impacted stool that will not come out, or absence of a bowel movement in 4 to 5 days. These symptoms occur with stool impaction and bowel obstruction, which are serious complications of constipation. Eighty percent of patients receiving chemotherapy experience fatigue. 26 Fatigue is the feeling of tiredness. 27 Fatigue can be caused by cancer its self, treatments for cancer such as chemotherapy or radiation therapy, and the side effects of therapy including anemia, electrolyte abnormalities, dehydration, malnutrition, lack of physical activity, lack of sleep, pain, or emotional distress. 26 Fatigue can affect how patients feel physical, emotionally, and spiritually, as well as interfere with the ability to function or socialize. 26 Patients usually report having fatigue within 1 to 2 days after the first chemotherapy treatment, throughout therapy, and weeks to months and sometimes even a year after treatment.
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Caring Ambassadors Lung Cancer Choices, 2nd Edition Since fatigue can be caused by many different factors, a combination of treatment approaches is necessary. Fatigue can be managed by maintaining a healthy diet, avoiding long naps during the day (keep under 1 hour), postponing activities that are not essential, doing moderate physical activity such as walking, and participating in relaxation activities such as yoga, massage, or acupuncture. 26-27 Treating problems such as pain, sleep disturbance, infection, or anemia also decrease fatigue. Symptomatic anemia related fatigue is sometimes treated with blood transfusions or red blood cell stimulating products. Steroids or medications that increase patient's appetite can also be helpful. It is helpful to keep a record or weekly diary of the onset of fatigue, factors that aggravate or improve fatigue, and the effect of fatigue on activities of daily living. 27 Patients should contact their provider if they experience an increase in their fatigue, the inability to get out of bed or think clearly, fever, or Alopecia is temporary or permanent hair loss. This occurs because chemotherapy damages the hair follicle, causing the hair to break. Some chemotherapy drugs cause thinning of the hair without complete hair loss. Chemotherapy may affect the hair on the head, eyelashes, eyebrows, face, underarm, leg, and pubic area. Most people report a tingling sensation before the hair falls out, usually two to three weeks after the first chemotherapy treatment. Hair loss cannot be prevented, so being prepared is important. Before starting chemotherapy, the patient may purchase hats, scarves, or wigs. After hair loss, it is important to protect the skin from extreme warm (sun burn) or cold temperatures and to keep the skin lubricated with ointments and creams to avoid dryness. After chemotherapy is completed, the hair may grow back however this usually begins within three months after the last treatment.28 Changes to the skin and nail may occur due to chemotherapy especially if a patient is being treated Cutaneous (Skin and Nail) Changes with a targeted chemotherapy such as Afatinib, Cetuximab, Erlotinib, or Gefitinib. Rash is the most common skin related side effect from targeted therapies. 29 The rash is usually acneform (looks like acne with pustules or white heads) and is located on the face, chest, abdomen, or thighs.30 It is important for the patient to not pop the pustules as this could lead to infection requiring antibiotics. Patient's skin can also become itchy, scaly, rough, and dry. Bathing with nonirritating soaps and water as well as applying fragrance free emollients, creams, and lotions to moisturize the skin can provide symptom relief. Patients should avoid bath salts or lotions that contain alcohol as they can dry out the skin. Epidermal growth factor receptor inhibitors can cause paronychia or nail fold swelling and cracking in the fingers and toes. Skin and nail changes can wax and wane and/or spontaneously resolve. 29 For the most part, reducing the dose or interrupting therapy for a brief period of time is the most effect way to manage moderate to severe cutaneous reactions related to targeted therapies. 29-30 At times topical or oral antibiotics may be given to help reduce symptoms related to targeted therapy induced acneiform rashes. Both, targeted and non-targeted based chemotherapies can cause the skin may become sensitive to sunlight therefore staying out of direct sunlight and wearing sunscreen is important. Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer Mucositis is inflammation and ulceration of the lining of the mouth, throat, and digestive tract. This occurs Mucositis due to direct cellular kill by chemotherapy as well as the release of oxidative, inflammatory and metabolic by-products. 31 Mucositis can be very painful and irritating requiring pain medications and alteration in nutritional intake. Symptoms may include an abnormal sensation in the mouth, redness, swelling, sores, difficulty swallowing, bleeding, and mouth pain. Mucositis can also cause nausea and vomiting. Medications can be used to prevent mucositis from developing or becoming worse. It is important to maintain good nutrition and oral hygiene to prevent abnormal bacteria or fungi from growing inside the mouth. It also is important to keep the mouth and lips moist to prevent cracking which can lead to infection. The patient should avoid using a hard bristle toothbrush and alcohol-based mouthwash, which can irritate the lining of the mouth and gums. 32 The patient should notify the practitioner for any changes in the mouth, inability to swallow, pain or discomfort when swallowing, sores or white patches in the mouth or on the tongue, bleeding from the gums, fever, or other signs of infection. Medications and oral rinses (saline solutions, baking soda solutions) may alleviate symptoms. The platinum-based chemotherapy drugs that are used to treat NSCLC, such as cisplatin and Ototoxicity carboplatin, may cause inner ear damage, high pitch hearing loss, and ringing in the ears (tinnitus). Other medications such as antibiotics and diuretics can produce the same effects. Hearing loss is painless and may not be noticed until it becomes severe and irreversible. Signs and symptoms of hearing loss include turning the head while having a conversation, increasing the volume of the television or radio, or unclear, muffled, or quiet sounds. The patient should report changes in hearing to the practitioner, who may examine the ears and determine if hearing loss has occurred. A hearing test (audiogram) may be done before, during, or after chemotherapy to assess hearing. Changes in vision and eye toxicities are side effects of systemic chemotherapies as well as targeted therapies. Ocular Toxicities Some of the most common eye problems experienced by patients include: blepharitis (inflammation of the eyelids, redness, crusting and flaking of the skin on the lids); conjunctivitis (inflammation and redness of the conjunctiva); epiphora (excessive tear production); photophobia (sensitivity to light); photopsia (ocular pain); trichomeglay (long eyelashes that get misdirected or go inward instead of outward); diplopia (double vision), visual floaters and blurry vision. Treatment for vision changes includes artificial tears or lubricants, topical steroids, anti-inflammatory medications, good eye hygiene, warm compresses, avoiding light exposure, and occasional y discontinuation of chemotherapy. Prompt referral to an ophthalmologist is important when a patient experiences severe pain, swelling, redness, or sudden onset of any type of visual impairment. 33-34 Cognitive change also known as "chemo brain" is a decrease in mental sharpness. Chemotherapy is one Cognitive Dysfunction of many causes of cognitive dysfunction. Patients can develop memory impairment, difficulty
Caring Ambassadors Program 2014
Caring Ambassadors Lung Cancer Choices, 2nd Edition completing tasks, the inability to learn new skills, trouble with word finding or completing sentences, misplacing objects, confusing dates, and overall feeling mentally slow. Cognitive changes can be short or long term. Patient should notify their providers when "chemo brain" interferes with their normal daily activities and their ability to work. 35 Some chemotherapy drugs can cause damage to nerve fibers and lead to peripheral neuropathy, Peripheral Neuropathy causing numbness, tingling, burning, and loss of vibratory sensation in the hands and feet.36 Peripheral neuropathy may interfere with normal activities and may cause difficulties performing fine motor movements such as buttoning a shirt, writing, or picking up utensils. Sensing pain or changes in temperature, driving, walking, cooking, or brushing the teeth may also become difficult. Extremely hot or cold temperatures may aggravate numbness and tingling and may cause severe burns or frostbite injury. Therefore, extreme caution is necessary. It is recommended patients wear gloves near the refrigerator/freezer and potholders when cooking. Falls should be avoided by removing objects from the floor, securing area rugs, cleaning spills, and illuminating a room before entering. Some medications may be given for peripheral neuropathy. Although several medications are not approved by the United States Food and Drug Administration for the treatment of peripheral neuropathy, they may decrease the unpleasant symptoms of numbness and tingling. These medications include antidepressants, anti-seizure medication such as gabapentin, topical creams that contain capsaicin, and anesthetic creams or patches that contain lidocaine. Other helpful therapies may include acupuncture, physical therapy, massage, occupational therapy, and transcutaneous electrical nerve stimulation. The patient should contact the provider if the peripheral neuropathy becomes worse, interferes with self-care or activities of daily living, or causes stumbling, falling, loss of balance, injury, or muscle spasms in the mouth, jaw, fingers, or toes.
Conclusion
The patient should speak with the oncology provider or nurse about specific side effects that may be expected from the chemotherapy, and how these side effects will be prevented and treated. It is important to keep a list of the presence and severity of all side effects experienced. This list may give the oncology provider valuable information about how to treat the symptoms. In additional, the patient should keep the telephone numbers of their providers and clinic available in case of severe illness, high fever, or symptoms that require immediate medical attention. Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer
Appendix 1. Chemotherapy Drugs for Non-small Cell Lung Cancer and Common Side
Effects*
Chemotherapy Drug
Common Side Effects
Kidney damage (nephrotoxicity), nausea and (Cis-diamminedichloroplatinum, CDDP, vomiting, decrease in the red cell, white cell, and platelet counts (bone marrow suppression), nerve damage (neurotoxicity), high pitch hearing loss and ringing in the ears (ototoxicity), eye damage (ocular toxicity), metallic taste of foods, loss of appetite, hair loss (alopecia), infertility, liver function changes, possible vascular events (heart attack, stroke, clot formation), SIADH (syndrome of inappropriate antidiuretic hormone secretion) Decrease in the red cell, white cell, and platelet (VP-16, VePesid®) counts (bone marrow suppression), nausea and vomiting, anorexia, hair loss (alopecia), inflammation and ulceration in the mouth, throat, and intestines (muscositis), infusion reaction (fever, chills, shortness of breath, increased heart rate, facial and tongue swelling, low blood pressure), metallic taste in the mouth during infusion, redness at the injection site, skin changes (radiation recall reaction – skin reaction that occurs on an areas that has been previously radiated) Kidney damage (nephrotoxicity), nausea and vomiting, decrease in red cell, white cell, and platelet counts (bone marrow suppression), nerve damage (neurotoxicity), hair loss (alopecia), infertility, liver function changes, allergic reaction (skin rash, itchiness, hives, shortness of breath, low blood pressure) Decrease in red cell, white cell, and platelet counts (bone marrow suppression), infusion reaction (skin rash, flushing, redness, shortness of breath, low blood pressure), nerve damage (neurotoxicity), heart rate changes, hair loss (alopecia), inflammation and ulceration in the mouth, throat, and intestines (muscositis), diarrhea, liver and kidney function changes, nail bed changes (onycholysis)
Caring Ambassadors Program 2014
Caring Ambassadors Lung Cancer Choices, 2nd Edition Chemotherapy Drug
Common Side Effects
Decrease in the red cell, white cell, and platelet counts (bone marrow suppression), nausea and vomiting, constipation, diarrhea, inflammation and ulceration in the mouth, throat, and the intestines (muscositis), liver function changes, injury and inflammation the vein, nerve changes (neurotoxicity), hair loss (alopecia), general fatigue, infusion reaction (shortness of breath, low blood pressure, facial flushing, rash), SIADH (syndrome of inappropriate antidiuretic hormone secretion) Decrease in the red cell, white cell, and platelet counts (bone marrow suppression), nausea and vomiting, flu like symptoms (fever, muscle and body aches, chills, headaches), liver function changes, pulmonary toxicities( shortness of breath or drug induced pneumonitis), infusion reaction (facial flushing and swelling, headache, shortness of breath, low blood pressure), protein or blood in the urine, skin rash on the chest and extremities, swelling of the lower extremities, radiation recall skin reactions. Decrease in the white blood cell count (neutropenia), allergic reaction (skin rash, skin redness, low blood pressure, shortness of breath), fluid retention, dry itchy skin rash (maculopapular rash), hair loss (alopecia), inflammation and ulceration in the mouth, throat, and intestines (muscositis), diarrhea, nausea and vomiting, generalized fatigue, liver and kidney function changes, phlebitis or swelling at the injection site. Decrease in the red cell, white cell, and platelet counts (bone marrow suppression), skin rash, diarrhea, nausea and vomiting, inflammation and ulceration in the mouth, throat and intestines (mucositis), fatigue, changes in the liver and kidney function Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer Chemotherapy Drug
Common Side Effects
Albumin-Bound Paclitaxel Myelosupression (decrease in white blood cells, red blood cells, and platelets), ocular or visual disturbances, fatigue, weakens, alopecia, nausea, vomiting, mucositis, liver toxicities, neurotoxicity's (peripheral neuropathy and paresthesias), injection site reactions, cardiac toxicities (chest pain, high blood pressure, elevated heart rate, blood clot in the lungs), peripheral edema (swelling of the extremities) Myelosuppression, nausea, vomiting, diarrhea, abdominal pain, headache, fever, fatigue, alopecia (hair loss), liver toxicities, blood in the *Adapted from Chu E and Devita VT. Physicians' Cancer Chemotherapy Drug Manual (2014).37
Caring Ambassadors Program 2014
Caring Ambassadors Lung Cancer Choices, 2nd Edition Appendix 2. Targeted Therapy Drugs for Non-small Cell Lung Cancer and Common Side
Effects*
Targeted
Mutation
Side Effects
40 mg orally, once daily Diarrhea, rash, nail fold swelling in Take 1 hour before or the fingers and toes (paronychia), 2 hours after a meal dry skin, bullous and exfoliative skin disorders, decrease appetite, stomatitis, lung toxicity (interstitial lung disease), liver toxicities, inflammation of cornea (keratitis), visual changes, increase risk for heart dysfunction Given intravenously Nose bleeds (epistaxis), high blood once every 3 weeks pressure, decreased wound healing, gastrointestinal perforation, protein in the urine (proteinuria), infusion reaction (fever, chills, hives, facial flushing, fatigue, headache, shortness of breath, lip swelling, low blood pressure), possible lung bleeding (pulmonary hemorrhage) or vascular events (heart attack, stroke), dizziness, depression 750 mg orally, once Diarrhea, nausea, vomiting, daily on an empty abdominal pain, liver toxicities, lung stomach, do not take toxicity (interstitial lung within 2 hours of a disease/pneumonitis), heart dysfunction, decreased heart rate, high blood sugar (hyperglycemia), fatigue, decrease appetite, constipation Given intravenously Itchy and dry skin, acne skin rash on face and chest, nail fold swelling in the fingers and toes (paronychial inflammation), lung toxicity (cough, shortness of breath, interstitial lung disease), infusion reaction (fever, chills, rash, flushing, fatigue, headache, shortness of breath, lip swelling, low blood pressure), low magnesium, generalized malaise Caring Ambassadors Program 2014 Chapter 3: Chemotherapy for Non-small Cell Lung Cancer Targeted
Mutation
Side Effects
250 mg orally, twice Liver and kidney toxicities, decrease heart rate and contractility, lung toxicity (decrease in pulmonary function, pneumonia, interstitial lung disease/pneumonitis, shortness of breath, cough) visual disturbances (double and blurry vision, floaters/flashes, visual brightness, reduced visual acuity), diarrhea, nausea, vomiting, decrease appetite, fatigue, peripheral neuropathy 150 mg orally, once Dry and itchy skin, acneiform rash on face and chest, diarrhea, nausea and vomiting, mucositis, increased cough, shortness of breath, fever, liver function changes, anorexia, pink eye (conjunctivitis), inflammation of cornea (keratitis), nail changes (paronychia), hair growth abnormalities (alopecia, thinning of hair with increased fragility, darkening and increased thickness of eyelashes and eyebrows), possible GI hemorrhage 250mg orally, daily High blood pressure, dry itchy skin, acneiform rash, liver function changes, anorexia, nausea and vomiting, mucositis, conjunctivitis, inflammation of cornea (keratitis), abnormal eyelash growth, inflammation of the eyelash follicle (blepharitis), possible coughing up blood or GI hemorrhage 50mg orally daily for Decrease in the red cell, white cell, and platelet counts (bone marrow suppression), high blood pressure, yellowish discoloration in the skin, skin rash, dryness or cracking of the skin, nose bleeds (epistaxis), fatigue, diarrhea, altered taste, abdominal pain, inflammation and ulceration in the mouth, throat, and intestines (muscositis), increase risk for heart dysfunction, adrenal insufficiency, low thyroid function (hypothyroidism) *Adapted from Chu E and Devita VT. Physicians' Cancer Chemotherapy Drug Manual (2014).37
Caring Ambassadors Program 2014
Caring Ambassadors Lung Cancer Choices, 2nd Edition References
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