LUNG CANCER: TREATMENT OF NON-SMALL CELL LUNG CANCER IN THE ELDERLY

LUNG CANCER: TREATMENT OF NON-SMALL CELL LUNG CANCER IN THE ELDERLY Authored by: Bryan J. Schneider, M.D. and Gregory P. Kalemkerian, M.D. Division of Hematology/Oncology, Department of Internal Medicine University of Michigan, Ann Arbor, MI 48109-0848 INTRODUCTION Lung cancer is the leading cause of cancer-related death in the United States for both men and women. In the United States, 80% of patients with lung cancer have non-small cell lung cancer, while the remaining 20% have small cell lung cancer. Non-small cell lung cancer is a "catch all" term for a group of cancers originating in the lung that includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. All of these diseases are treated in a similar fashion, and are therefore discussed under the general heading of non-small cell lung cancer. The average age at diagnosis of lung cancer is 68 years, which means that more than half of all patients with non-small cell lung cancer are older than 65 years of age and one-third are over 70 years old. WHAT DOES “ELDERLY” MEAN? Prior to making treatment recommendations, the oncologist must assess an individual patient's ability to tolerate the various types of treatment that are available to treat cancer, including surgery, radiation therapy, and chemotherapy, used either alone or in combination with each other. Patient age must be considered because some treatments may not be tolerated as well by older patients as by younger individuals. In previous studies, the definition of an "elderly" patient has varied from 65 years of age or older to 75 years of age or older. A more functional definition of "elderly" has been proposed as follows:"when the health status of a patient begins to interfere with oncological (cancer) decision-making guidelines"(1). This definition also takes into account the fact that a patient's other medical problems could interfere with treatment of the cancer. Age, by itself, does not generally prevent the use of the best available therapy. However, with increasing age comes a higher propensity for chronic illnesses that may impair a patient's functional ability and alter his or her ability to tolerate aggressive anticancer treatment. Debility caused by the cancer or by other illnesses may change the balance between the potential risks and benefits of a specific treatment. Another relevant issue is that although lung cancer is very common in elderly patients, most of the available data regarding the optimal treatment of lung cancer comes from clinical trials in which the vast majority of patients are significantly younger than 65 years of age. Few elderly patients are enrolled into clinical trials, perhaps due to the greater chance that they may have other medical problems that exclude them from a trial or due to potential bias on the part of their physicians or the elderly patients themselves against enrollment in trials studying investigational, and potentially more aggressive, therapies. It is only in the past 10 years that trials have been specifically designed to evaluate the potential benefits and risks of treatment in elderly patients, but even in clinical trials designed for patients 70 years of age or older, the average age of treated patients tends to be in the early 70s with few patients over the age of 80 participating in such trials. CHOOSING TREATMENT Two of the most important pieces of information needed to decide on the appropriate treatment for patients with non-small lung cancer are the stage of the disease and the performance status of the patient. Cancer staging is a way to describe the extent of the disease. It also helps the oncologist guide treatment decision-making and offer general information to the patient regarding overall prognosis. In non-small cell lung cancer, staging is done by looking at the size of the tumor, involvement of lymph nodes within the chest, and the presence of cancer spread to areas outside of the chest, such as the brain, liver, bones, or adrenal glands. Table 1 presents the most common staging system used by oncologists for patients with non-small cell lung cancer(2). Table 1. International Staging System for Lung Cancer, 1997 Revision The performance status of a patient helps an oncologist define how the lung cancer or other medical problems are affecting the patient's ability to function. The worse the performance status, the more likely it is that the patient will have significant complications during aggressive treatment. Table 2 presents one performance status scale commonly used by oncologists to gauge an individual patient's level of daily functioning. Patients with non-small cell lung cancer and a performance status of 3 or 4 are usually not candidates for surgery or chemotherapy. In addition to evaluating general performance status, a careful assessment of heart function, lung function, and other chronic illnesses may be required before treatment recommendations can be made. Table 2. Zubrod or Eastern Cooperative Oncology Group (ECOG) Performance Scale TREATMENT OF PATIENTS WITH STAGE I OR STAGE II DISEASE SURGERY Stage I or II non-small cell lung cancer typically means that the cancer is confined to the lung and there is no or minimal lymph node involvement. The most effective treatment for patients with stage I or II disease is to surgically remove the cancer by cutting out all or part of the involved lung. Studies have shown that elderly patients with good lung and heart function and a good performance status can tolerate lung cancer surgery as well as younger patients with a similar chance for cure (3-7). Older patients may need to undergo a more rigorous evaluation of their heart and lung function prior to surgery to ensure that surgery can be performed safely and with an acceptable risk of long-term complications. For patients with stage I disease, 60-80% can be cured by surgical removal of the cancer. For those with stage II disease, 40-50% of patients can be cured by surgery. For more information on surgery, see the article in CancerNews titled "Lung Cancer: Who is a Candidate for Surgery?" RADIATION THERAPY Radiation therapy is the treatment of cancer by a beam of high energy x-rays directed at the part of the body affected by the cancer. Like surgery, it is a local treatment that only can kill cancer cells within the area being treated, not throughout the whole body. Some elderly patients may not be able to undergo surgical removal of stage I or II non-small cell lung cancer because of a significant medical problem, such as a recent heart attack or poor lung function due to emphysema. In these situations, radiation therapy targeted to the main lung tumor and to lymph nodes to which the cancer has spread may be the best treatment option for potential cure. However, the chance for cure in patients with stage I disease treated with radiation therapy is only 20-30%, significantly lower than that seen with surgery (8). For patients who can tolerate surgery and undergo complete removal of a stage I or II cancer, radiation therapy is not typically recommended because it has not been shown to improve the chance for cure and can cause potentially serious side-effects in patients with underlying lung disease. CHEMOTHERAPY Chemotherapy is a term that pertains to many different drugs, usually given through a vein, used to try to kill cancer cells wherever they might be in a patient's body. Chemotherapy is not typically used as the sole treatment for stage I or II non-small cell lung cancer because by itself it cannot cure the disease. Sometimes it is used after surgery as adjuvant therapy (meaning "in addition to" the primary treatment, in this case surgery). In several recent clinical trials, chemotherapy has been shown to decrease the chance for cancer recurrence and improve the chance for cure in some patients who have undergone complete surgical removal of stage IB, II, or IIIA non-small cell lung cancer. All of these studies were randomized trials in which half of the enrolled patients received chemotherapy after surgical removal of the tumor and the other half received no further therapy. The first of these adjuvant trials, called IALT, demonstrated a 5% decrease in cancer recurrence rate and a 4% improvement in survival in patients treated with cisplatin-based chemotherapy compared to those receiving no further therapy after surgical removal of stage IB, II, or III non-small cell lung cancer (9). While the benefit of chemotherapy in this trial may seem small, a recurrence of the cancer is usually incurable, meaning that chemotherapy given after surgery can prevent some people from dying of the cancer. Importantly, patients over 75 years of age were not allowed to participate in this trial and the average age of patients enrolled was only 59 years. Therefore, it is not clear whether the benefit of chemotherapy seen in this trial would also occur in an older population of patients. The second of these trials, called JBR.10, demonstrated a 15% improvement in survival in patients treated with the chemotherapy combination of cisplatin plus vinorelbine compared to those receiving no further therapy after surgical removal of stage IB or II non-small cell lung cancer (10). The third recent adjuvant chemotherapy trial, called CALGB 9633, demonstrated a 12% improvement in survival in patients treated with carboplatin plus paclitaxel compared to those receiving no further therapy after surgical removal of stage IB non-small cell lung cancer (11). Although the JBR.10 and CALGB 9633 trials did not limit the age of potential participants, the average age of patients enrolled in both of these trials was 61 years and few patients were over 75 years of age. The most recent of the adjuvant trials, called the ANITA trial, demonstrated an 8% improvement in survival in patients treated with cisplatin plus vinorelbine compared to those receiving no further therapy after surgical removal of stage IB, II, or IIIA non-small cell lung cancer (11). As in the first trial mentioned above, patients over the age of 75 years were not allowed to participate in the ANITA trial. Overall, adjuvant chemotherapy is now recommended for patients who have undergone complete removal of stage IB, II, or III non-small cell lung cancer and have recovered from surgery within two months without significant complications. Clearly, the oncologist must carefully evaluate every patient to ensure that the potential benefits of chemotherapy outweigh the risk of serious side-effects of treatment. If adjuvant chemotherapy is given, the chemotherapy should consist of four cycles of cisplatin or carboplatin in combination with another chemotherapy agent, usually vinorelbine, paclitaxel, or etoposide. While age alone should not be a deterrent to receiving adjuvant chemotherapy, the oncologist must keep in mind that very few elderly patients were involved in the clinical trials that determined the benefits of this treatment. TREATMENT OF PATIENTS WITH STAGE III DISEASE Stage III disease usually means that the cancer has directly extended outside the lung into other structures within the chest or has spread to the lymph nodes outside of the lung within the middle of the chest, called the mediastinum. The mediastinum is the area in the chest between the lungs where the heart, major blood vessels, esophagus, and windpipe are located. Unfortunately, stage III non-small cell lung cancer is more difficult to cure than earlier stage disease. Surgery is usually not an option due to the extent of disease and its proximity to vital organs. Most patients with stage III disease are treated with a combination of radiation therapy and chemotherapy. However, the particular type of treatment recommended for an individual patient is dependant on his or her performance status, degree of prior weight loss, and overall medical condition. For patients with significant functional impairment, radiation therapy alone may be recommended. Although the chance for cure with radiation alone is small (13), the addition of chemotherapy may add an unacceptable risk of side-effects and further debility in these patients. Patients who are able to care for themselves, but require some assistance, or who have had significant weight loss may be candidates for chemotherapy followed by radiation therapy. This sequential form of chemotherapy and radiotherapy offers a better chance for cure than radiation therapy alone, but also introduces potential side-effects from chemotherapy. Patients who are in good physical condition and have had minimal weight loss, may be candidates for radiation therapy and chemotherapy given together at the same time. This treatment offers the best chance for cure, with 15-20% of patients alive 5 years after the diagnosis (14, 15). However, concurrent radiation and chemotherapy is also associated with greater short-term and long-term side-effects that may not be tolerated by patients who are frail, have had significant weight loss, or have other major medical problems. There are several acceptable ways of combining chemotherapy and radiation therapy, but the optimal method has not yet been defined. Radiation is typically administered once a day, Monday though Friday, for 6 weeks. Chemotherapy can be given as two cycles of intermittent treatment with combinations of drugs such as cisplatin plus etoposide or carboplatin plus etoposide, or treatment once a week during radiation therapy with a combination such as carboplatin plus paclitaxel. The combination of carboplatin plus etoposide probably offers the most tolerable risk of side-effects (16). The common side-effects of concurrent chemotherapy plus radiation therapy include fatigue, drops in the blood counts that can increase the risk of infection or bleeding, irritation of the esophagus that can cause difficulty swallowing, and inflammation of the lungs that can cause cough or shortness of breath. No clinical trials have yet been designed to specifically study the treatment of elderly patients with stage III non-small cell lung cancer. Some trials that included both young and elderly patients have compared the effects of the treatment on elderly patients versus the younger ones. One such analysis was done of a trial comparing sequential to concurrent chemotherapy plus radiation therapy (17). All patients enrolled in this trial had a good performance status, but only 17% were elderly (70 years old or older). The elderly patients on this trial were just as likely to complete treatment and obtained as much benefit from treatment as younger patients. Although the elderly patients had a higher risk of short-term side-effects, specifically low blood counts and esophageal irritation, they did not have any greater risk of long-term complications. Another analysis was done of a study comparing chemotherapy plus concurrent chemotherapy given once or twice a day in which 26% of patients were 70 years old or older (18). Again, the chance for cure was similar in younger and elderly patients, but the risks of side-effects, particularly low blood counts and inflammation of the lungs, was higher in elderly patients. Overall, these data suggest that concurrent chemotherapy plus radiotherapy is both tolerable and beneficial in elderly patients with stage III non-small cell lung cancer who are in good overall physical condition. TREATMENT OF PATIENTS WITH STAGE IV DISEASE Stage IV disease usually means that the cancer has spread through the bloodstream to another location in the body, either to the other lung or to organs outside of the chest such as the brain, liver, adrenal glands, or bones. Unfortunately, stage IV non-small cell lung cancer is not curable with any currently known treatments. Surgery and radiation therapy are local treatments that cannot eradicate cancer once it has spread to a distant site. Therefore, the primary treatment option for patients with stage IV disease is chemotherapy, and the goal of treatment is to prolong good quality of life. Standard treatment consists of a combination of two chemotherapy drugs, usually cisplatin or carboplatin plus another agent such as paclitaxel, gemcitabine, docetaxel or vinorelbine. The use of cisplatin in elderly patients may result in a greater risk because of its particular side-effects which include impairment of kidney function, damage to the nerves in the hands and feet, nausea and vomiting with resultant dehydration, and hearing loss. Cisplatin should clearly be avoided in elderly patients that already have, or are at specific risk for, one of these conditions. Despite these concerns, analyses of two studies that treated patients of all ages with a cisplatin-containing regimen have shown that ¡°fit¡± elderly patients with a good performance status had no significant differences in response to treatment or survival when compared to the younger patients on the trials (19,20). Several studies have specifically studied the use of chemotherapy in elderly patients with advanced non-small cell lung cancer. One of the central questions of these studies has been the potential role of single-drug treatment based on the rationale that one drug would result in fewer side-effects than combinations of chemotherapy drugs, and may therefore lead to improved quality of life and duration of survival in the elderly population (21-24). The ELVIS trial randomized patients age 70 years or older to receive either vinorelbine or no chemotherapy (21). Patients receiving vinorelbine reported better quality of life and were found to have longer survival than those who received no chemotherapy. A second trial, the MILES trial, compared two different types of single-drug therapy, gemcitabine or vinorelbine, against the combination of the two drugs given together in patients 70 years of age or older with advanced non-small cell lung cancer (22). Treatment with the combination of drugs did not improve patient survival or quality of life, but was associated with a greater risk of significant side-effects. Overall, while it appears that ¡°fit¡± elderly patients can tolerate and may benefit from treatment with a combination of chemotherapy agents, there is little data to suggest that such combinations of drugs offer any benefit over single-drug chemotherapy in the elderly patient population. Recently, newer drugs that can more specifically target lung cancer cells have been developed and have been shown to benefit some patients with advanced non-small cell lung cancer. In general, these drugs have more tolerable side-effects than standard chemotherapy since they are more specifically aimed at the cancer cells. Erlotinib is one such drug that has been approved for use in patients with advanced non-small cell lung cancer. Erlotinib is a pill that can result in tumor shrinkage and improvement in duration of survival in patients with non-small cell lung cancer that has recurred after initial treatment with standard chemotherapy (25). To date, specific studies of erlotinib in elderly patients have not been reported, and the drug does have potential side-effects, such as diarrhea, that may be particularly problematic in the elderly population. Thus far, we know that women, non-smokers, people of East Asian heritage, and those with adenocarcinoma seem to benefit the most from treatment with erlotinib (26). As stated earlier, radiation therapy cannot treat all sites of disease in patients with advanced non-small cell lung cancer, but it can be very useful in alleviating distressing symptoms, such as pain due to bone invasion or cough and shortness of breath due to the obstruction of an airway. In addition, radiation therapy is the primary treatment for patients with cancer that has spread to the brain. Finally, some elderly patients with advanced, incurable non-small cell lung cancer may elect not to undergo therapy because of the potential for serious side-effects. This is certainly a reasonable option, and support services such as hospice care can aggressively treat symptoms and work to improve quality of life, with the goal of keeping patients functional and feeling well for as long as possible. Hospice care can offer much needed assistance for both the patient and their family in dealing with the physical, emotional, spiritual, and practical aspects of living with a terminal disease. CONCLUSION In the past, elderly patients were frequently not offered standard treatment for lung cancer purely based on their age and the concern that they would not be able to tolerate therapy. While this may be the case in a fair number of elderly patients who have significant limitations in their functional ability or other medical illnesses, it has now become clear that many elderly patients can tolerate and benefit from standard treatments for lung cancer. In recent years, there has been a greater focus on the development of clinical trials that specifically address lung cancer treatment in the elderly and several excellent reviews of this topic have been published in the medical literature (27-31). It is important to stress that performance status is the most significant indicator of how well an individual patient will tolerate therapy and how well they will do with the disease in general. Patients with a limited performance status have a shorter survival time and are much less likely to benefit from treatment. However, "fit" elderly patients with a good performance status may be good candidates for standard therapy, and may gain just as much benefit from such therapy as younger patients.

Additional Authors:
Gregory P. Kalemkerian, M.D.

Works Cited:

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Douillard JY, Rosell R, Delena M, et al. ANITA: Phase III adjuvant vinorelbine and cisplatin versus observation in completely resected (stage I-III) non-small-cell lung cancer patients: final results after 70-month median follow-up. J Clin Oncol 23(16S): 624s, 2005, Abstract #7013. 13. Lonardi F, Coeli M, Pavanato G, et al. Radiotherapy for non-small cell lung cancer in patients aged 75 and over: safety, effectiveness and possible impact on survival. Lung Cancer 28:43-50, 2000. 14. Furuse K, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small cell lung cancer. J Clin Oncol 17:2692-9, 1999. 15. Curran WJ, Scott CB, Langer CJ, et al. Long-term benefit is observed in a phase III comparison of sequential vs. concurrent chemo-radiation for patients with unresected stage III NSCLC: RTOG 9410. Proc Am Soc Clin Oncol 22:621, 2003, Abstract #2499. 16. Lau DH, Crowley JJ, Gandara DR, et al. Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide and radiation for poor-risk stage III non-small-cell lung cancer. J Clin Oncol 16:3078-81, 1998. 17. Langer CJ, Hsu C, Curran WJ, et al. Elderly patients with locally advanced non-small cell lung cancer benefit from combined modality therapy: secondary analysis of RTOG 94-10. Proc Am Soc Clin Oncol 21:299a, 2002, Abstract #1193. 18. Schild SE, Stella PJ, Geyer SM, et al. The outcome of combined-modality therapy for stage III non-small cell lung cancer in the elderly. J Clin Oncol 21:3201-6, 2003. 19. Fossella FV, Belani CP. Phase III study (TAX 326) of docetaxel-cisplatin and docetaxel-carboplatin versus vinorelbine-cisplatin for the first line treatment of advanced/metastatic non-small cell lung cancer: analyses in elderly patients. Proc Am Soc Clin Oncol, 22:629, 2003, Abstract #2528. 20. Lilenbaum RC, Herndon JE 2nd, List MA, et al. 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Part I: non-small cell lung cancer. Lung Cancer 39:233-53, 2002.

A Word about Clinical Trials

When you or a loved one are diagnosed with cancer, it is important to know all of the treatment options available in order to make the best decision about your cancer treatment. This may include clinical trials, which are research studies designed to evaluate new cancer treatment options. Clinical trials test the safety and effectiveness of treatments, many of which are only available through participating in a clinical trial. Trials evaluate new anti-cancer drugs, unique approaches to surgery and radiation therapy, and new combinations of treatments. In the United States, the Food and Drug Administration (FDA) oversees the conduct of clinical trials.

What does the FDA do?

The FDA is a government agency that is responsible for making certain that the food we eat and the drugs we take are safe. The FDA does not make drugs or directly test drugs to determine if they are safe and effective. The FDA's role is to oversee the research conducted by pharmaceutical companies, university research centers, and physicians to make certain that federal regulations governing research are being followed.

The FDA requires that the drug company's plan must be reviewed by community research review board (IRB), and that patients participating in the clinical trial are informed about the trial and consent to participate. Once the drug company has completed its clinical trials, the data are tabulated and submitted to the FDA in an application known as a New Drug Application (NDA). The FDA evaluates the outcomes reported in the NDA and determines whether the new drug will be approved and made available to patients in the United States. In order to be approved, the drug must be safe and effective.

Can I get a drug before it is approved by the FDA?

Until a drug receives FDA approval, it cannot be sold and the drug company may only provide it to patients through clinical trials. Furthermore, each clinical trial has specific criteria that patients must meet to be included. Occasionally, a cancer patient who is not eligible for a clinical trial may receive a promising unapproved drug, if the patient's doctor, the drug company, and FDA each agree. The FDA's primary interest is helping to ensure that the drug company's research will not subject cancer patients in the clinical trial to undue risks. The FDA drug review process guarantees that the risks and benefits of a cancer drug have been carefully considered before it is approved and helps to ensure the public that marketed drugs are safe and effective.

How can I learn more about a drug that has been approved?

The FDA requires that all drugs have an information document for healthcare providers and consumers called a “package insert.” This document is a summary of the essential scientific information needed for the safe and effective use of the drug. You can ask your doctor for this information. Also, most package inserts are available on the internet. A package insert typically includes the following information:

• Chemical structure
• Information about how the body absorbs, distributes, metabolizes, and excretes the drug
• Results from some clinical trials
• What specific circumstances the drug is used for
• Dosing and administration schedules
• Side effects
• Contraindications

It is important to understand that once it has been determined that a drug is safe and it is approved by the FDA, physicians often use the drug for the treatment of medical conditions other than the specific condition that the FDA has approved it for.

Are all clinical trials the same?

Development of new anticancer drugs and treatment strategies occurs in four phases. Each phase is designed to determine specific information about the potential new treatment such as its risks, safety, and effectiveness compared to standard therapy. The hope is that the new therapy will be an improvement over the previous standard therapy.

Phase I Trials: This phase is probably the most important step in the development of a new drug or therapy. Phase I therapy may produce anti-cancer effects and a small number of patients may benefit, however, the primary goals of this phase are to determine safety issues, which include:

• The maximum tolerated dose of the treatment,
• The manner in which the drug works in the body,
• The toxic side effects related to different doses, and
• Whether toxic side effects are reversible.

Phase I trials usually involve a small number of patients for whom other standard therapies have failed or no known alternative therapy is available. Upon completion of phase I trials, the information that has been gathered is used to begin phase II trials.

Phase II Trials: Phase II trials are designed to determine the effectiveness of the treatment in a specific patient population at the dose and schedules determined in phase I. These trials usually require a slightly higher number of patients than phase I trials. In general, all of the patients participating in a phase II trial will receive the treatment that is being investigated. Drugs or therapies that are shown to be active in phase II trials may become standard treatment or be further evaluated for effectiveness in phase III trials.

Phase III Trials: Phase III trials compare a new drug or therapy with a standard therapy in a randomized and controlled manner in order to determine proof of effectiveness. Phase III trials require a large number of patients to measure the statistical validity of the results because patient age, sex, race, and other unknown factors could affect the results. To obtain an adequate number of patients, several physicians (investigators) from different institutions typically participate in phase III clinical trials.

Phase IV Trials: Once the drug or treatment is approved and becomes part of standard therapy, the manufacturer of the drug may elect to initiate phase IV trials. This phase includes continued evaluation of the treatment effectiveness and monitoring of side effects as well as implementing studies to evaluate usefulness in different types of cancers.

There is currently no single source of all clinical trials. The following are clinical trial resources that patients may wish to visit:

• NCI's Web site at www.cancer.gov
• ECancerTrials National Clinical Trials Database

http://cancer.unm.edu/content.aspx?section=patients&id=23016

Questions to Ask Your Doctor about Cancer Treatment

Being educated and informed will help you make the best decisions about your cancer treatment. Get all the information you can as early as possible concerning your evaluation, treatment, and possible side effects. The sooner you know about side effects and possible treatments, the more likely you are to protect yourself against them, or manage them more effectively.

Your doctor and nurse are your best sources of information, but you must remember to ask questions. There is no such thing as a dumb question. Don’t be afraid to ask anything that is on your mind. To make the most of your opportunities to learn from your health care providers, read as much as you can and make a list of questions before each appointment. Also, ask family, friends, and your support team to help you remember the questions. These approaches will help you talk more effectively with your doctor or nurse. Finally, you or your caregiver should consider taking notes during your visit to ensure you remember what you learned.

The following are some questions, grouped by topic, which you may wish to ask your nurse or physician:

Your Cancer
• Do you typically treat patients with my diagnosis?
• What stage is my cancer?
• Is there anything unique about my cancer that makes my prognosis better or worse?
• Should I get a second opinion?

Cancer Treatment
• What is the goal of treatment?
• To cure my cancer or stop it from growing?
• What are my treatment options?
• How can each treatment option help me achieve my goal of therapy?
• What risks or potential side effects are associated with each treatment?
• What research studies (“clinical trials”) are available?
• Are there any clinical trials that are right for me?
• How long will I receive treatment, how often, and where?
• How will it be given?
• How will I know if the treatment is working?
• How might a disruption in my chemotherapy dose or timing affect my results?
• How and when will I be able to tell whether the treatment is working?
• What are the names of all the drugs I will be taking?
• Can I talk with another of your patients who has received this treatment?
• Are there any resources or Web sites you recommend for more information?

Tests
• What types of lab tests will I need?
• Will I need x-rays and scans?
• Can you explain the results of my complete blood count (CBC)?
• Are there tests for the genetic make-up of my cancer?
• Will I benefit from having my cancer evaluated for its genetic make-up?
• How frequently will I get the tests?

Side Effects of Treatment
• What possible side effects should I prepare for?
• When might they start?
• Will they get better or worse as my treatment goes along?
• How can I prepare for them or lessen their impact?
• Are there treatments that can help relieve the side effects? What are they? Do you usually recommend or prescribe them?
• Which risks are most serious?
• Will I require blood transfusions? Why?
• How can I best monitor myself for complications related to either my disease or my treatment?

Protecting Against Infection
• Will my type of chemotherapy put me at risk for a low white blood cell count and infection?
• Can I help protect myself against infection right from the start of chemotherapy, instead of waiting until problems develop?
• Am I at special risk for infection?
• What are the signs of infection?
• How serious is an infection?
• How long will I be at risk for infection?
• What should I do if I have a fever?
• How are infections treated?

Daily Activities
• How will my cancer treatment affect my usual activities?
• Will I be able to work?
• Will I need to stay in the hospital?
• Will I need someone to help me at home?
• Will I need help taking care of my kids?
• Are there any activities I should avoid during my chemotherapy?

What to Expect After Treatment
• What happens after I complete my treatment?
• How can I best continue to monitor myself for complications related to either my disease or my treatment?
• What kind of lab tests will I need?
• How frequently should I get those lab tests?
• What types of x-rays and scans will I need?
• How often do I need to come in for checkups?
• When will you know if I am cured?
• What happens if my disease comes back?

Optimizing Your Treatment

By proactively understanding and managing aspects of your treatment, you can help ensure the best possible outcome from treatment and maintain some degree of control in your life. Things you can do to optimize treatment of cancer are:

• Get informed
• Stay organized
• Discuss the effectiveness of treatment
• Work with your physician to select the best treatment for you

Don’t forget that fighting cancer is not a challenge you should face alone. It is a team effort that involves family, friends, and your healthcare team. Don’t overlook the strength that can come from having your support network by your side. In order to ensure optimal treatment, consider the following:

Get informed: A new diagnosis of cancer can be a shock, making you feel out of control and overwhelmed. Getting informed can help alleviate these feelings. Seek out many resources to investigate your treatment options for your type and stage of cancer. Resources should include your healthcare team, second opinions, books, the internet, and other patients with your disease. As you learn, identify the specific questions that only your doctor can answer.

Most importantly, work toward understanding your diagnosis and stage of disease, goals of therapy, treatment plan, benefits of treatment, and possible side effects. Following a diagnosis of cancer, the most important step is to accurately define the stage of your disease. Staging is a system that describes how far the cancer has spread. (Keep in mind that some cancers, such as leukemia, may not be staged.) Each stage of cancer may be treated differently. In order for you to begin evaluating and discussing treatment options with your healthcare team, you need to find out from your doctor the correct stage of your cancer.

Stay organized: Develop a system for keeping all the information that you gather organized, such as laboratory and test results, admissions and consultation information, and additional instructions. Keep a folder or three-ring binder with all your information in one location.

Discussing the effectiveness of treatment: It is important that you and your caregivers are able to evaluate treatment options and to understand how cancer treatments are compared so that you can work with your healthcare team to make informed treatment choices. Understanding the goals of a specific therapy, as well as the risk and benefits it poses, will help you decide which treatment is most appropriate for your situation. Patients typically receive cancer treatment in order to cure the cancer, prolong the duration of their life or alleviate symptoms caused by the cancer and improve their quality of life. These potential benefits of treatment must be balanced against the risks of treatment. Some risks posed by various cancer treatments may include time away from family and friends, uncomfortable side effects of therapy and/or long-term complications or death.

The most common term used to describe the effectiveness of cancer treatment is remission. Remission means that the cancer has disappeared and can no longer be measured using existing technology. Oncologists use the terms partial and complete remission to describe partial or complete disappearance of cancer after treatment. A cancer cannot be cured if a remission is not obtained; however, a remission does not always ensure that a cancer is cured. The best ways to evaluate the benefits of treatment are to examine the duration of remission, survival, and disease-free survival (cure). Since it often takes many years to determine whether a new treatment is better than a previous treatment, remission rates may be useful for comparing therapies when patients have not been evaluated long enough to know whether the chance of cure or survival is improved.

Treatment of cancer is associated with risks. It is important that you evaluate the risks and benefits of treatment within the context of the overall goal of receiving cancer therapy.

Cancer treatment may be inconvenient, prolonged, or unavailable close to home. These are important considerations when evaluating treatment options, but not typically mentioned in medical journals reporting the results and benefits of new treatments.

Select your optimal treatment: Cancer treatment varies depending upon your type of cancer, stage of cancer, and overall condition. Additionally, treatment options may vary depending on whether or not the goal of treatment is to cure the cancer, keep the cancer from spreading, or to relieve the symptoms caused by cancer. You and your physician will consider all of these factors as you work on selecting your optimal treatment.

Introduction to Cancer Treatment

Overview of Cancer Treatments

Choice of cancer treatment is influenced by several factors, including the specific characteristics of your cancer; your overall condition; and whether the goal of treatment is to cure your cancer, keep your cancer from spreading, or to relieve the symptoms caused by cancer. Depending on these factors, you may receive one or more of the following:

• Surgery
• Chemotherapy
• Radiation therapy
• Hormonal therapy
• Targeted therapy
• Biological therapy

One or more treatment modalities may be used to provide you with the most effective treatment. Increasingly, it is common to use several treatment modalities together (concurrently) or in sequence with the goal of preventing recurrence. This is referred to as multi-modality treatment of the cancer.

Surgery

Surgery is used to diagnose cancer, determine its stage, and to treat cancer. One common type of surgery that may be used to help with diagnosing cancer is a biopsy. A biopsy involves taking a tissue sample from the suspected cancer for examination by a specialist in a laboratory. A biopsy is often performed in the physician’s office or in an outpatient surgery center. A positive biopsy indicates the presence of cancer; a negative biopsy may indicate that no cancer is present in the sample.

When surgery is used for treatment, the cancer and some tissue adjacent to the cancer are typically removed. In addition to providing local treatment of the cancer, information gained during surgery is useful in predicting the likelihood of cancer recurrence and whether other treatment modalities will be necessary.

Learn more about surgery.

Chemotherapy

Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. Chemotherapy is different from surgery or radiation therapy in that the cancer-fighting drugs circulate in the blood to parts of the body where the cancer may have spread and can kill or eliminate cancers cells at sites great distances from the original cancer. As a result, chemotherapy is considered a systemic treatment.

More than half of all people diagnosed with cancer receive chemotherapy. For millions of people who have cancers that respond well to chemotherapy, this approach helps treat their cancer effectively, enabling them to enjoy full, productive lives. Furthermore, many side effects once associated with chemotherapy are now easily prevented or controlled, allowing many people to work, travel, and participate in many of their other normal activities while receiving chemotherapy.

Learn more about chemotherapy treatment and the management of side effects.

Radiation Therapy

Radiation therapy, or radiotherapy, uses high-energy rays to damage or kill cancer cells by preventing them from growing and dividing. Similar to surgery, radiation therapy is a local treatment used to eliminate or eradicate visible tumors. Radiation therapy is not typically useful in eradicating cancer cells that have already spread to other parts of the body. Radiation therapy may be externally or internally delivered. External radiation delivers high-energy rays directly to the tumor site from a machine outside the body. Internal radiation, or brachytherapy, involves the implantation of a small amount of radioactive material in or near the cancer. Radiation may be used to cure or control cancer, or to ease some of the symptoms caused by cancer. Sometimes radiation is used with other types of cancer treatment, such as chemotherapy and surgery, and sometimes it is used alone.

For more information, go to Radiation Therapy.

Hormonal Therapy

Hormones are naturally occurring substances in the body that stimulate the growth of hormone sensitive tissues, such as the breast or prostate gland. When cancer arises in breast or prostate tissue, its growth and spread may be caused by the body’s own hormones. Therefore, drugs that block hormone production or change the way hormones work, and/or removal of organs that secrete hormones, such as the ovaries or testicles, are ways of fighting cancer. Hormone therapy, similar to chemotherapy, is a systemic treatment in that it may affect cancer cells throughout the body.

Targeted Therapy

A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes.

Conventional cancer treatments, such as chemotherapy and radiation therapy, cannot distinguish between cancer cells and healthy cells. Consequently, healthy cells are commonly damaged in the process of treating the cancer, which results in side effects. Chemotherapy damages rapidly dividing cells, a hallmark trait of cancer cells. In the process, healthy cells that are also rapidly dividing, such as blood cells and the cells lining the mouth and GI tract are also damaged. Radiation therapy kills some healthy cells that are in the path of the radiation or near the cancer being treated. Newer radiation therapy techniques can reduce, but not eliminate this damage. Treatment-related damage to healthy cells leads to complications of treatment, or side effects. These side effects may be severe, reducing a patient's quality of life, compromising their ability to receive their full, prescribed treatment, and sometimes, limiting their chance for an optimal outcome from treatment.

Biological Therapy

Biological therapy is referred to by many terms, including immunologic therapy, immunotherapy, or biotherapy. Biological therapy is a type of treatment that uses the body’s immune system to facilitate the killing of cancer cells. Types of biological therapy include interferon, interleukin, monoclonal antibodies, colony stimulating factors (cytokines), and vaccines.

Personalized Cancer Care

There is no longer a “one-size-fits-all” approach to cancer treatment. Even among patients with the same type of cancer, the behavior of the cancer and its response to treatment can vary widely. By exploring the reasons for this variation, researchers have begun to pave the way for more personalized cancer treatment. It is becoming increasingly clear that specific characteristics of cancer cells and cancer patients can have a profound impact on prognosis and treatment outcome. Although factoring these characteristics into treatment decisions makes cancer care more complex, it also offers the promise of improved outcomes.

The idea of matching a particular treatment to a particular patient is not a new one. It has long been recognized, for example, that hormonal therapy for breast cancer is most likely to be effective when the breast cancer contains receptors for estrogen and/or progesterone. Testing for these receptors is part of the standard clinical work-up of breast cancer. What is new, however, is the pace at which researchers are identifying new tumor markers, new tests, and new and more targeted drugs that individualize cancer treatment. Tests now exist that can assess the likelihood of cancer recurrence, the likelihood of response to particular drugs, and the presence of specific cancer targets that can be attacked by new anti-cancer drugs that directly target individual cancer cells.

To learn more about personalized cancer care for two common types of cancer, visit the following:

• Breast Cancer
• Colon Cancer

Diagnosing Cancer

What is a cancer diagnosis?
Diagnosis is not the same as detection. Cancer may be detected when symptoms or abnormalities, such as a lump or growth, are recognized by a patient or doctor. After a cancer is detected, it still must be carefully diagnosed.

A diagnosis is an identification of a particular type of cancer. When making a diagnosis, the initial signs and symptoms are investigated through a variety of tests in order to identify whether cancer is causing them and, if so, what type of cancer it is. For example, breast cancer may be detected when a patient notices a lump, but it must be carefully evaluated with a number of tests in order to determine an accurate diagnosis. The diagnosis describes what type of breast cancer it is (i.e. “ductal” if it started in the ducts of the breast or “lobular” if it started in the lobes) and how advanced it is.

What is a cancer stage?
Following a diagnosis of cancer, the most important step is to accurately determine the stage of cancer. Stage describes how far the cancer has spread. (Some cancers, such as leukemia, may not be staged.) Each stage of cancer may be treated differently. In order for you to begin evaluating and discussing treatment options with your healthcare team, you need to know the correct stage of your cancer.

There are many staging systems, but TNM is the most common. “T” refers to the size of the tumor, “N” to the number of lymph nodes involved, and “M” to metastasis. TNM staging measures the extent of the disease by evaluating these three aspects and assigning a stage, which is usually between 0-4. Generally, the lower the stage, the better the treatment prognosis (outcome).

• Stage 0 – precancer
• Stage 1 – small cancer found only in the organ where it started
• Stage 2 – larger cancer that may or may not have spread to the lymph nodes
• Stage 3 – larger cancer that is also in the lymph nodes
• Stage 4 – cancer in a different organ from where it started

How is prognosis determined?
The probable course and/or outcome of the cancer is called the prognosis. Identifying factors that indicate a better or worse prognosis may help you and your doctor plan your treatment. There are many factors that help determine your prognosis. Some of these include:

• Your age
• Your level of physical fitness
• Size of your cancer
• Stage of your cancer
• Aggressiveness of your cancer (cancer cells that are growing and dividing rapidly are considered more aggressive)

Your doctor will evaluate all possible factors to determine your prognosis.

Recently, the genetic make-up of cancer is being increasingly recognized as an important prognostic factor. For example, some genes have been associated with an aggressive course or tendency to recur. Identification of these in an early stage cancer may indicate a poor prognosis. Some research suggests that the genetic make-up of the cancer may be even more important for determining prognosis than the stage of the cancer.

How is cancer diagnosed?
Diagnosing cancer involves the use of a variety of tests that provide details about abnormal cells, which may have been detected through routine medical examinations, self-examination, or reported symptoms. More information about these cells must be gathered in order to identify them as malignant (cancerous) or non-malignant (non-cancerous), and if they are malignant, to determine how serious (aggressive) the particular cancer cells are. Aggressive cancers grow and spread more quickly than less-aggressive or “indolent” cancers. There are many types of tests specifically designed to evaluate cancer:

• A pathology report is based on observation of abnormal cells under a microscope.
• Diagnostic imaging involves visualization of abnormal masses using high tech machines that create images, such as x-rays, computed tomography (CT), positron emission test (PET), magnetic resonance imaging (MRI), and combined PET/CT.
• Blood tests measure substances in the blood that may indicate how advanced the cancer is or other problems related to the cancer.
• Tumor marker tests detect substances in blood, urine, or other tissues that occur in higher than normal levels with certain cancers.
• Special laboratory evaluation of DNA involves the identification of the genetic make-up—the DNA—of the abnormal cells.

For more information about diagnostic tests, visit the Testing Center.

How does diagnosis determine treatment?
Historically, a combination of pathological assessment (laboratory evaluation using a microscope) and diagnostic imaging has been used to identify the type of cancer and its stage, and then the treatment. Stage indicates how extensive the cancer is and how much it has spread. Staging usually involves determining the size of the primary tumor and evaluating whether it has remained in the tissue in which it started, whether it has invaded other nearby organs or tissues, and whether cancer cells have spread to distant locations in the body. The cancer is then assigned a stage on a predetermined scale of numbers and letters, for example stage I, II, IIIa, IIIb, IV, etc. The higher number and letter combination indicates more extensive spread, and therefore a more serious condition. Treatment is often selected based on the stage of disease. Higher stage cancers typically receive very aggressive treatments and lower stage disease less aggressive treatment.

However, research has indicated that identifying the stage of disease may not be the most accurate technique for determining how aggressive it is. For example, some early stage diseases may recur or progress even after treatment, while some late stage cancers may stay in remission. These findings suggest that there may be factors other than how the cancer looks under a microscope and how far it has spread at the time of diagnosis that may better indicate the likelihood that a given cancer will recur and/or progress.

Human genomics, which is the study of the entire genetic material of humans, has provided invaluable tools for identifying the genetic components of cancers. The mapping of the human genome, which consists of 30,000 to 70,000 genes, has laid the ground work for understanding the role those genes play in human health and disease. Cancer is many different diseases; however, one aspect of all cancers that is similar is damage to the DNA resulting in uncontrolled cell growth. Identifying the genes for each cancer type that are involved in the capacity grow and spread may provide valuable prognostic information.

As improvements are made in the special laboratory techniques used to identify the genetic make-up of cancers, this genetic information may become a better predictor of cancer aggressiveness and outcome than stage, which has been the diagnostic indicator of choice in the past. Additionally, this genetic information will likely play an increasing role in directing treatment. Specifically, the genes involved in each cancer may indicate more aggressive treatment for some cancers and less aggressive treatment for others.

WHAT CANCER

What Is Cancer?

Newly Diagnosed
A new diagnosis of cancer can be a shock, making you feel out of control and overwhelmed. Getting informed can help alleviate these feelings. Remember, very few cancers require emergency treatment; you have time to learn about your diagnosis and treatment options, ask questions, and get a second opinion. This section is designed to help you address your initial questions before you move forward with your treatment.

What is Cancer?
Cancer is not one disease, but many diseases that occur in different areas of the body. Each type of cancer is characterized by the uncontrolled growth of cells. Under normal conditions, cell reproduction is carefully controlled by the body. However, these controls can malfunction, resulting in abnormal cell growth and the development of a lump, mass, or tumor. Some cancers involving the blood and blood-forming organs do not form tumors but circulate through other tissues where they grow.

A tumor may be benign (non-cancerous) or malignant (cancerous). Cells from cancerous tumors can spread throughout the body. This process, called metastasis, occurs when cancer cells break away from the original tumor and travel in the circulatory or lymphatic systems until they are lodged in a small capillary network in another area of the body. Common locations of metastasis are the bones, lungs, liver, and central nervous system.

The type of cancer refers to the organ or area of the body where the cancer first occurred. Cancer that has metastasized to other areas of the body is named for the part of the body where it originated. For example, if breast cancer has spread to the bones, it is called "metastatic breast cancer" not bone cancer.

How did I get cancer?
Although every patient and family member wants to know the answer to this question, the reason people develop cancer is not well understood. There are some known carcinogens (materials that can cause cancer), but many are still undiscovered. We do not know why some people who are exposed to carcinogens get cancer and others do not. The length and amount of exposure are believed to affect the chances of developing a disease. For example, as exposure to cigarette smoking increases, the chance of developing lung cancer also increases. Genetics also plays an important role in whether an individual develops cancer. For example, certain types of breast cancer have a genetic component.

What’s next?
Following your diagnosis of cancer, your reaction may be one of shock and disbelief. If you have been told that chemotherapy or radiation therapy are an important part of your treatment, many unpleasant images may come to mind. But as you move beyond that initial shock to begin the journey of surviving your cancer, you have many good reasons to be optimistic. Medicine has made—and continues to make—great strides in treating cancer and in making cancer treatment more tolerable, both physically and emotionally.

No one would call cancer a normal experience, but by proactively managing aspects of your treatment, you can maintain a sense of normalcy in your life. Fighting cancer is not a challenge you face alone. It's a team effort that involves family, friends, and your healthcare team. Don't overlook the strength that can come from having your support network by your side.