Primary chemotherapy refers to chemotherapy administered 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 therapy 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 initiation 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 childhood cancers include acute lymphoblastic leukemia, Burkitt’s lymphoma, Wilms’ tumor, and embryonal rhabdomyosarcoma.
Neoadjuvant chemotherapy refers to the use of chemotherapy in patients who present with localized cancer for which alternative local therapies, such as surgery, exist but which have been shown to be less than completely effective. At present, neoadjuvant therapy is most often administered in the treatment of anal cancer, bladder cancer, breast cancer, gastroesophageal cancer, laryngeal cancer, locally advanced non-small cell lung cancer (NSCLC), osteogenic sarcoma, and locally advanced rectal cancer. For diseases such as anal cancer, gastroesophageal cancer, laryngeal cancer, NSCLC, and rectal cancer, optimal clinical benefit is derived when chemotherapy is administered with radiation therapy either concurrently or sequentially. The goal of the neoadjuvant approach is to reduce the size of the primary tumor so that surgical resection can be made easier and more effective. In addition, with rectal cancer and laryngeal cancer, the administration of combined modality ther apy prior to surgery can result in sparing of vital normal organs, such as the rectum or larynx. In general, additional chemotherapy is given for a defined period of time, usually 3–4 months, after surgery has been performed.
One of the most important roles for cancer chemotherapy is as an adjuvant to local treatment modalities such as surgery, and this has been termed adjuvant chemotherapy. In this setting, chemotherapy is administered after surgery has been performed, and the goal of chemotherapy 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 potential 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, NSCLC, Wilms’ tumor, anaplastic astrocytoma, and osteogenic sarcoma. Patients with primary malignant melanoma at high risk of local or systemic recurrence derive clinical benefit from adjuvant treatment with the biologic agent interferon α (IFN-α), although this treatment 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 postmenopausal women with early-stage breast cancer whose breast tumors express the estrogen receptor (see Chapter 40 for additional details). 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.