Chapter 081. Principles of Cancer Treatment (Part 23)

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Mucositis Irritation and inflammation of the mucous membranes particularly afflicting the oral and anal mucosa, but potentially involving the gastrointestinal tract, may accompany cytotoxic chemotherapy. Mucositis is due to damage to the proliferating cells at the base of the mucosal squamous epithelia or in the intestinal crypts. Topical therapies, including anesthetics and barrier-creating preparations, may provide symptomatic relief in mild cases. Palifermin or keratinocyte growth factor, a member of the fibroblast growth factor family, is effective in preventing severe mucositis in the setting of high-dose chemotherapy with stem cell transplantation for hematologic malignancies. It may also prevent mucositis from radiation. ...

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Chapter 081. Principles of Cancer Treatment (Part 23) Mucositis Irritation and inflammation of the mucous membranes particularly afflicting the oral and anal mucosa, but potentially involving the gastrointestinal tract, may accompany cytotoxic chemotherapy. Mucositis is due to damage to the proliferating cells at the base of the mucosal squamous epithelia or in the intestinal crypts. Topical therapies, including anesthetics and barrier-creating preparations, may provide symptomatic relief in mild cases. Palifermin or keratinocyte growth factor, a member of the fibroblast growth factor family, is effective in preventing severe mucositis in the setting of high-dose chemotherapy with stem cell
transplantation for hematologic malignancies. It may also prevent mucositis from radiation. Alopecia Chemotherapeutic agents vary widely in causing alopecia, with anthracyclines, alkylating agents, and topoisomerase inhibitors reliably causing near-total alopecia when given at therapeutic doses. Antimetabolites are more variably associated with alopecia. Psychological support and the use of cosmetic resources are to be encouraged, and "chemo caps" that reduce scalp temperature to decrease the degree of alopecia should be discouraged, particularly during treatment with curative intent of neoplasms such as leukemia or lymphoma, or in adjuvant breast cancer therapy. The richly vascularized scalp can certainly harbor micrometastatic or disseminated disease. Gonadal Dysfunction and Pregnancy Cessation of ovulation and azoospermia reliably result from alkylating agent– and topoisomerase poison–containing regimens. The duration of these effects varies with age and sex. Males treated for Hodgkin's disease with mechlorethamine- and procarbazine-containing regimens are effectively sterile, whereas fertility usually returns after regimens that include cisplatin, vinblastine, or etoposide and after bleomycin for testicular cancer. Sperm banking before treatment may be considered to support patients likely to be sterilized by
treatment. Females experience amenorrhea with anovulation after alkylating agent therapy; they are likely to recover normal menses if treatment is completed before age 30 but unlikely to recover menses after age 35. Even those who regain menses usually experience premature menopause. As the magnitude and extent of decreased fertility can be difficult to predict, patients should be counseled to maintain effective contraception, preferably by barrier means, during and after therapy. Resumption of efforts to conceive should be considered in the context of the patient's likely prognosis. Hormone replacement therapy should be undertaken in women who do not have a hormonally responsive tumor. For those patients who have had a hormone-sensitive tumor primarily treated by a local modality, conventional practice would counsel against hormone replacement, but this issue is under investigation. Chemotherapy agents have variable effects on the success of pregnancy (Chap. 7). All agents tend to have increased risk of adverse outcomes when administered during the first trimester, and strategies to delay chemotherapy, if possible, until after this milestone should be considered if the pregnancy is to continue to term. Patients in their second or third trimester can be treated with most regimens for the common neoplasms afflicting women in their childbearing years, with the exception of antimetabolites, particularly antifolates, which have notable teratogenic or fetotoxic effects throughout pregnancy. The need for anticancer chemotherapy per se is infrequently a clear basis to recommend
termination of a concurrent pregnancy, although each treatment strategy in this circumstance must be tailored to the individual needs of the patient. Chronic effects of cancer treatment are reviewed in Chap. e13. Biologic Therapy The goal of biologic therapy is to manipulate the host-tumor interaction in favor of the host. Theoretically, biologic approaches should reflect a bell-shaped dose-response curve where the maximum biologic effect is less than the MTD. However, empirical trial and error has led to the discovery that a number of biologic treatment approaches may produce antitumor effects, but nearly all of them are most active at their MTD. As a class, biologic therapies may be distinguished from molecularly targeted agents in that many biologic therapies require an active response (e.g., reexpression of silenced genes, or antigen expression) on the part of the tumor cell or on the part of the host (e.g., immunologic effects) to allow therapeutic effect. This may be contrasted with the more narrowly defined antiproliferative or apoptotic response that is the ultimate goal of molecularly targeted agents discussed above. However, there is much commonality in the strategies to evaluate and use molecularly targeted and biologic therapies.