Treatment Of Advanced Cancer: Chemotherapy

The most important aspect of cancer chemotherapy trials conducted in the 1960s and realized in the 1970s was the demonstration that drugs could cure patients with some types of advanced cancer. The most important initial goal of the more intensive drug treatment programs is similar to the goal of surgery and radiation therapy for localized tumor—that is, to erase all clinical evidence of disease (complete remission). The length of time the patient remains free of disease after all therapy is discontinued is used as an indication of the magnitude of the reduction of tumor cell number. These indicators of successful treatment have been valid, and survival has improved commensurate with an increase in the rates and duration of complete remission for metastatic cancers when drug combinations have been compared with single agents.

Cancers can generally be grouped into categories according to the effectiveness of systemic treatment. Cancers for which current chemotherapeutic programs have major activity and are clinically quite useful. In some cases, patients are curable even though the body burden of tumor cells is very high. In most cases maximum benefit is achievable only by drug combinations. In Hodgkin's disease, acute childhood leukemia, diffuse large cell lymphomas, and testicular tumors, disease-free survival after cessation of treatment extends to over 15 years. Considering the tumor volume in most of these patients at the time of treatment (± 10" cells), these results are quite remarkable. The break in the survival curve varies for each disease. A 2-year disease-free interval from the end of treatment is sufficient to consider patients cured with such virulent, rapidly growing tumors as choriocarcinoma, Burkitt's lymphoma, and diffuse large cell lymphomas, while 4 or more years are required to evaluate the results of treatment in Hodgkin's disease, acute childhood leukemia, breast cancer, and testicular cancer. Widespread use of these treatment programs has resulted in marked improvement in relative survival rates concomitant with a sharp decrease in national mortality in patients with Hodgkin's disease and other lymphomas, testes cancer, acute leukemia of childhood, other pediatric neoplasms, ovarian carcinoma, and premenopausal women with breast cancer. Chemotherapy has moderate and useful activity in the cancers, although cure is not generally possible once the diseases have metastasized. Adjuvant studies have proved positive in non-small cell lung cancer and head and neck cancers that, if confirmed, could change the outlook of these diseases in a major way.

Tumors are frequently thought of as resistant to treatment, but on occasion significant palliation can be provided for patients by the careful use by an experienced physician of existing chemotherapeutic agents. However, studies using adjuvant 5-fluo-rouracil plus levamisole have shown a statistically significant improvement in relapse-free and overall survival at 4 years in Duke's B2 and С colon cancer, and the combination of 5-fluorouracil and radiation therapy has been shown to improve survival in patients with locally unresectable pancreatic cancer. These studies are being reconfirmed in larger-scale clinical trials. Biological therapy with interleukin 2 and activated lymphocytes has produced significant regression of metastases in patients with colon, renal, lung cancer, and malignant melanoma; and preliminary results with specific monoclonal antibodies have shown useful responses in a few patients with colorectal and pancreas cancer and malignant melanoma.