Principles of Cancer Therapy - Other Modalities

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Endocrine Therapy
Additive or ablative endocrine therapy can influence the course of some cancers. Endocrine therapy is not curative; it is only palliative. Orchiectomy has significant palliative value in metastatic prostate cancer, commonly prolonging survival 3 to 5 yr. Its efficacy is based on the testosterone-dependent population of prostate cancer cells. Other cancers with hormone receptors on their cells (eg, breast, endometrium, ovary) can often be palliated by hormone ablative therapy. This success led to the use of hormones as pharmacologic therapy for such tumors. Estrogen effectively palliates prostate cancer but increases the risk of heart disease. These observations led to treatment with gonadotropin secretory inhibitors. Leuprolide, a synthetic analog of gonadotropin-releasing hormone, inhibits gonadotropin secretion and resultant gonadal androgen production and is as effective for the palliation of prostate cancer as is orchiectomy. Even more complete androgen blockage can be achieved by adding an oral antiandrogen (flutamide or bicalutamide), which limits androgen binding to its receptor; this combination appears to increase disease-free survival by 6 to 12 mo over leuprolide or orchiectomy alone.

Similarly, estrogen ablation (by oophorectomy) provides palliation in advanced breast cancer. Tamoxifen, an oral hormone, can bind to estrogen receptors on breast cancer cells and is as effective for palliation as is oophorectomy. It is a particularly effective therapy for metastatic breast cancer in the postmenopausal woman. As an adjuvant therapy in breast cancer, it prolongs the duration of disease-free survival, improves cure rate in receptor-positive patients by 20 to 30%, and reduces the risk of contralateral breast cancer by about 60%. For details of endocrine therapy, see Table 144-2.

Biologic Response Modifiers
Interferons, interleukins, and tumor necrosis factor (TNF) are biologic proteins that function in immune (protective) responses. They are synthesized by cells of the immune system when invaded by viruses as a physiologic protective response. In pharmacologic amounts, they have palliative efficacy in some cancers.

Interferons have demonstrated activity in selected cancers. In hairy cell leukemia, complete response rates of 60 to 80% have occurred. In chronic myelogenous leukemia, up to 20% of patients can achieve a complete response (Philadelphia chromosome-negative status). Interferon can prolong disease-free survival (12 to 24 mo) after effective chemotherapy in myeloma and some forms of lymphoma. Survival is somewhat prolonged in patients with melanoma and renal cell cancer. Cosmetic palliation occurs in Kaposi’s sarcoma. Significant toxicities of interferon include fatigue, nausea, leukopenia, chills and fever, and myalgias.

Interleukins, primarily the lymphokine interleukin-2 produced by activated T cells, have been used with modest palliative effect in renal cell cancer. Several other interleukins are under study, as is TNF.

Hyperthermia and Cryotherapy
Heating tumor beds (to 41° C [105.8° F]) to enhance cell kill using drugs or radiation has been tried with only trivial efficacy. Cryosurgery (using a probe directly into the tumor mass) provides modest palliation in liver cancer and inoperable breast cancer.

RELATED STORIES:
Management of Adverse Effects   Principles of Cancer Therapy

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