3 - Selection of Treatment for the Patient with Cancer

Editors: Skeel, Roland T.

Title: Handbook of Cancer Chemotherapy, 7th Edition

> Table of Contents > Section I - Basic Principles and Considerations of Rational Chemotherapy > Chapter 3 - Selection of Treatment for the Patient with Cancer

Chapter 3

Selection of Treatment for the Patient with Cancer

Ronald T. Skeel

I. Setting treatment goals

A. Patient perspective

Although most often patients come to the physician looking for a medical perspective on what can be done about their cancer, it is critical that physicians and other health care professionals remember that unless we know what the patient's goals are, our ideas and plans of therapy may not address the patient's needs. As a consequence, it is critical for the physician to ask the patient to participate in setting treatment goals because it is the patient who must undergo the rigors of treatment and be willing to abide by its consequences. Whereas the physician's medical recommendations are most commonly accepted, some patients reject them as inappropriate for them for a variety of reasons. Some ask the physician for another recommendation, and others seek the opinion of a second physician. The physician must clearly present the reasons for the treatment recommendations and why they seem to be the best ways to achieve the treatment objective. The physician has the obligation to make a treatment recommendation, but the patient always has the right to reject that advice without fear that the physician will be upset, will dislike the patient, or will refuse to continue to give the patient care.

B. Medical perspective

Before a physician decides on a course of treatment to recommend for a patient with cancer, an achievable medical goal of treatment must be clearly defined. If the goal is to cure the patient of cancer, the strategy of therapy is likely to be different from the strategy chosen if the purpose is to prolong life, or to relieve symptoms. To propose the goal of therapy, the physician must be

familiar with the natural history and behavior of the cancer to be treated
knowledgeable about the principles and practice of therapy for each of the treatment modalities that may be effective in that cancer
well grounded in the ethical principles of the treatment of patients with cancer
familiar with the theory and use of antineoplastic agents
informed about the particular therapy for the cancer in question
aware of the patient's individual circumstances, including stage of disease, performance status, social situation, psychological status, and concurrent illnesses.

Armed with this information and with the treatment goals in mind, the physician can develop a course of treatment, and make a recommendation to the patient.

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Components of the treatment plan include the following:

Should the cancer be treated at all, and, if so, is the treatment to be designed for cure, prolongation of life, or palliation of symptoms?
How aggressive should the therapy be to achieve the defined objective?
Which modalities of therapy will be used and in what sequence?
How will the treatment efficacy be determined?
What are the criteria for deciding the duration of therapy?

II. Choice of cancer treatment modality

A. Surgery

The oldest, most established, and still most effective way to cure most cancers is surgery. Surgery is selected as the treatment if the cancer is limited to one area and if it is anticipated that all cancer cells can be removed without unduly compromising vital structures. If it is believed that the patient can survive the surgery and return to a worthwhile life, surgery is recommended. Surgery is not recommended if the risk of surgery is greater than the risk of the cancer, if metastasis always occurs despite complete removal of the primary tumor, or if the patient will be left so debilitated, disfigured, or otherwise impaired that although cured of cancer, he or she feels that life is not worthwhile. If metastasis regularly (or always) occurs despite complete removal of the primary tumor, the benefits of removal of the gross tumor should be clearly defined before surgery is undertaken.

Most commonly, surgery is reserved for treatment of the primary neoplasm, although at times it may be used effectively to remove isolated metastases (e.g., in lung, brain, liver) with curative intent. Surgery is also used palliatively, such as for decompression of the brain in patients with glioma, or biliary bypass in patients with carcinoma of the pancreas. In nearly all nonhematologic cancers, a surgeon should be consulted to determine the role of surgery in the optimal treatment of the patient.

B. Radiotherapy

Radiotherapy is used for the treatment of local or regional disease when surgery cannot completely remove the cancer or when it would unduly disrupt normal structures or functions. In the treatment of some cancers, radiotherapy is as effective as surgery for eradicating the tumor. In this circumstance, factors such as the anticipated side effects of the treatment, the expertise and experience of local oncologists, and the preference of the patient may influence the choice of treatment.

One determinant of the appropriateness of radiotherapy is the inherent sensitivity of the cancer to ionizing radiation. Some kinds of cancer (e.g., the lymphomas and seminomas) are highly sensitive to radiotherapy. Other kinds (e.g., melanomas and sarcomas) tend to be less sensitive. Such considerations do not preclude the use of radiotherapy, however, and it is helpful to obtain an evaluation by the radiotherapist before initiating treatment so that treatment planning can take into consideration the possible contribution of this modality.

Although radiotherapy is frequently used as the primary or curative mode of therapy, it is also well suited to palliative

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management of problems such as bone metastases, superior vena cava syndrome, and local nodal metastases. The use of radiotherapy in the management of spinal cord compression and superior vena cava syndrome is discussed in Chapter 30.

C. Chemotherapy

Chemotherapy has as its primary role in the treatment of disease that is no longer confined to one site or region and has spread systemically. In the earliest days of chemotherapy, this interpretation directed its use to diseases that regularly presented in a disseminated form (e.g., leukemia) or after disease recurred following primary management with surgery or radiotherapy. It is now understood that widespread systemic micrometastases commonly occur early in cancer. These metastases are associated with certain predictive factors such as the axillary node metastases of carcinoma of the breast and the large tumor size and poorly differentiated histologic features of sarcomas or the cancer's genetic profile. Therefore, chemotherapy is now applied earlier to treat systemic disease. When this treatment is used for micrometastases, the response of an individual patient cannot be measured, unless the chemotherapy is used as a neoadjuvant, that is, before surgery or radiotherapy. Then tumor response may predict more important end points such as time to treatment failure and survival. More commonly, when the chemotherapy is used as an adjuvant after removal of visible disease, the effectiveness of therapy must be determined by comparing the survival (or disease free survival) of patients who receive therapy with that of similar (control) patients who do not receive therapy for the micrometastases. Chemotherapy also has a role in the treatment of localized or regional disease. These specialized uses are discussed in Chapter 31.

D. Biologic response modifiers

It has long intrigued cancer biologists that cancer does not occur randomly but preferentially selects specific populations: the young, the elderly, the immunosuppressed (certain types of cancer only), and those with a strong family history of cancer. These observations have led cancer biologists to postulate that some kind of biologic control over or proclivity toward the emergence of cancer exists, which some people have and others do not, at least at the time the cancer becomes established. One prime candidate for the mechanism of biologic control of cancer has been immunity. That immunity plays some role in controlling the development of cancer has been clearly demonstrated in animal models and a few, although not most, human neoplasms. Other biologic factors, including those controlled by oncogenes and tumor suppressor genes and their protein products, which affect the cancer cell directly or its environment, are becoming better defined, and are even more important than classic immunity in the development of cancer.

In an attempt to exploit and enhance the biologic control that is presumed to exist to some degree in everyone, or to counteract cancer-promoting factors that facilitate cancer growth, invasion, and metastases, a variety of agents called biologic response modifiers have been used in the treatment of cancer. Two classes of biologic response modifiers, the interferons and lymphokines (of which interleukin 2 is an example), have been studied for many years, and there is evidence of

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their substantial activity in some types of cancer Related, but separate, are molecular targeted agents that inhibit the activity of abnormally expressed protein products such as the constitutively activated Bcr-Abl tyrosine kinase in chronic myelogenous leukemia or other unique components of the cancer cell. This area of intensive research (as well as Wall Street interest) has begun to reach fruition and is expected to provide an increasingly important, although expensive, contribution to effective cancer therapy.

E. Combined-modality therapy

Neither surgery, radiotherapy, biotherapy, nor chemotherapy alone is appropriate for the treatment of all cancers. Frequently, patients present with cancer in which there is a bulky primary lesion, macroscopically evident regional disease, and presumed microscopic or submicroscopic systemic disease. For this reason, oncologists have turned to a multidisciplinary approach to the treatment of cancer, selecting two or more modalities of therapy for sequential or simultaneous use. This approach requires close cooperation among the surgical oncologist, radiation oncologist, and medical oncologist to provide the patient with the best overall treatment plan. Although combined-modality therapy is neither effective nor desirable for all kinds or stages of cancers, the regular practice of a multidisciplinary approach provides the best opportunity to exploit the advantages of each mode of treatment. Tumor Boards often serve as the forum for ensuring that patients will regularly have the benefit of various treatment perspectives.

III. Palliative care

The medical oncologist, who is also an internist, is often seen as the coordinator of cancer treatment. In this role, although the cancer is focused on, the broader perspective of the oncologist as a coordinator of the patient's care in partnership with the patient should not become obscured. Decisions about what therapy to use and how aggressively to treat the cancer are critically important to medically sound patient care. Decisions about when to stop active cancer treatment are also vitally important and may be among the most difficult responsibilities for the oncologist. It is critical that oncologists, who provide and profit from therapy, recognize the inherent conflict of interest in their dual role as care givers and drug salespersons.

Quality of life is often enhanced in patients responding to chemotherapy and other cancer treatments; it just as surely deteriorates more rapidly when the tumor does not respond to therapy and the patient experiences the toxicity of treatment along with the pain, fatigue, cachexia, and other symptoms of the cancer. For the 50% of patients with cancer who are not cured, the decision to stop antineoplastic therapy is just as important as the selection of chemotherapeutic regimens earlier in the disease. There comes a time when the best advice a physician can give is for the patient to forgo additional chemotherapy or any other active cancer treatment.

The introduction and rapid acceptance of hospice programs throughout the United States during the last 35 years reflect the need for this kind of care. Hospice programs have effectively addressed the special physical, psychological, social, and spiritual needs of patients approaching the end of life and have provided the unique skills required to maintain the best possible quality

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of life as long as possible. More recently, acute care hospitals have recognized that they, too, have patients who are at the end of life and need a special focus on the palliative aspects of their care. Yet, too often, physicians are reluctant to give up and are unable to recognize or accept when the patient will be helped more by an acknowledgment that active cancer therapy will not improve survival or enhance quality of life.

Oncologists and others caring for patients with cancer who have been trained as acute care physicians can learn specific techniques to enhance the quality of life from those who are experts in palliative care. For example, one might compare the quality of death in hospitalized patients given maintenance IV hydration with that of hospice home care patients offered oral fluids and mouth care to assuage thirst. The former method may result in an overhydrated, edematous patient who dies with an uncomfortable-sounding death rattle that is disconcerting to family and staff; the latter usually results in a visibly more comfortable patient who is more likely to die with less edema and without as much apparent respiratory distress.

Legitimate questions can also be raised about medical costs toward the end of life that are incurred when physicians give futile and marginal care. Development of guidelines by physicians and hospitals that define futile care, along with thoughtful consideration of when the therapy that is offered to patients has marginal value, may enable physicians to improve the quality of life for patients and at the same time hold down one component of the rising spiral of health care costs.

References Suggested Readings

Brody H, Campbell ML, Faber-Langendoen K, et al. Withdrawing intensive life-sustaining treatment recommendations for compassionate clinical management. Engl J Med 1997;336:6.

Emanuel EJ, Patterson WB. Ethics of randomized clinical trials. J Clin Oncol 1998;16:365-366.

Jacobson M, O'Malley AJ, Earle CC, et al. Does reimbursement influence chemotherapy treatment for cancer patients? Health Aff 2006;25:437-443.

Lundberg GO. American health care system management objectives: the aura of inevitability becomes incarnate. JAMA 1993;269:2254-2255.

Skeel RT. Measurement of quality of life outcomes. In: Berger AM, Portnoy RK, Weissman DE, eds. Principles and practice of palliative care and supportive oncology, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2002:1107-1122.

Taylor LM, Feldstein ML, Skeel RT, et al. Fundamental dilemmas of the randomized clinical trial process: results of a survey of the 1737 Eastern Cooperative Oncology Group investigators. J Clin Oncol 1994;12:1776-1805.