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Chapter: Basic & Clinical Pharmacology : Cancer Chemotherapy

Cancer Treatment Modalities

With present methods of treatment, about one third of patients are cured with local treatment strategies, such as surgery or radio-therapy, when the tumor remains localized at the time of diagnosis.


With present methods of treatment, about one third of patients are cured with local treatment strategies, such as surgery or radio-therapy, when the tumor remains localized at the time of diagno-sis. Earlier diagnosis might lead to increased cure rates with such local treatment. In the remaining cases, however, early microme-tastasis is a characteristic feature, indicating that a systemic approach with chemotherapy is required for effective cancer man-agement. In patients with locally advanced disease, chemotherapyis often combined with radiotherapy to allow for surgical resection to take place, and such a combined modality approach has led to improved clinical outcomes. At present, about 50% of patients who are initially diagnosed with cancer can be cured. In contrast, chemotherapy alone is able to cure less than 10% of all cancer patients when the tumor is diagnosed at an advanced stage.Chemotherapy is presently used in three main clinical settings:

primary induction treatment for advanced disease or for can-cers for which there are no other effective treatment approaches,neoadjuvant treatment for patients who present with localized disease, for whom local forms of therapy such as surgery or radia-tion, or both, are inadequate by themselves, (3) adjuvant treat-ment to local methods of treatment, including surgery, radiation therapy, or both.

Primary induction chemotherapy refers to chemotherapyadministered as the primary treatment in patients who present with advanced cancer for which no alternative treatment exists. This has been the main approach in treating patients with advanced metastatic disease, and in most cases, the goals of ther-apy are to relieve tumor-related symptoms, improve overall quality of life, and prolong time to tumor progression. Studies in a wide range of solid tumors have shown that chemotherapy in patients with advanced disease confers survival benefit when compared with supportive care, providing sound rationale for the early ini-tiation of drug treatment. However, cancer chemotherapy can be curative in only a small subset of patients who present with advanced disease. In adults, these curable cancers include Hodgkin’s and non-Hodgkin’s lymphoma, acute myelogenous leukemia, germ cell cancer, and choriocarcinoma, while the curable child-hood cancers include acute lymphoblastic leukemia, Burkitt’s lymphoma, Wilms’ tumor, and embryonal rhabdomyosarcoma.


Neoadjuvant chemotherapy refers to the use of chemotherapyin patients who present with localized cancer for which alternative local therapies, such as surgery, exist but which are less than com-pletely effective. At present, neoadjuvant therapy is most often administered in the treatment of anal cancer, bladder cancer, breast cancer, esophageal cancer, laryngeal cancer, locally advanced non-small cell lung cancer, and osteogenic sarcoma. For some of these diseases, such as anal cancer, gastroesophageal cancer, laryn-geal cancer, and non-small cell lung cancer, optimal clinical ben-efit is derived when chemotherapy is administered with radiation therapy either concurrently or sequentially.

One of the most important roles for cancer chemotherapy is as an adjuvant to local treatment modalities such as surgery or radia-tion therapy, and this has been termed adjuvant chemotherapy. The goal of chemotherapy in this setting is to reduce the incidence of both local and systemic recurrence and to improve the overall survival of patients. In general, chemotherapy regimens with clinical activity against advanced disease may have curative poten-tial following surgical resection of the primary tumor, provided the appropriate dose and schedule are administered. Adjuvant chemotherapy is effective in prolonging both disease-free survival (DFS) and overall survival (OS) in patients with breast cancer, colon cancer, gastric cancer, non-small cell lung cancer, Wilms’ tumor, anaplastic astrocytoma, and osteogenic sarcoma. Patients with primary malignant melanoma at high risk of local recurrenceor systemic metastases derive clinical benefit from adjuvant treat-ment with the biologic agent α-interferon, although this treat-ment must be given for 1 year’s duration for maximal clinical efficacy. Finally, the antihormonal agents tamoxifen, anastrozole, and letrozole are effective in the adjuvant therapy of postmeno-pausal women with early-stage breast cancer whose breast tumors express the estrogen receptor. However, because these agents are cytostatic rather than cytocidal, they must be administered on a long-term basis, with the standard recommendation being 5 years’ duration.

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