Perspectives on research in gynecologic oncology.

Gynecologic cancers present unusual opportunities to explore the fruits of well-designed clinical trials to assess the value of existing treatment using a combined modality approach soon after diagnosis. Cancers of the ovary and uterus have well-defined, familiar natural histories. Pathways of spread are clear and reasons for treatment failure are often blatantly obvious. In the case of ovarian cancer, regional treatment with surgery and radiotherapy has been relatively ineffective and generally has not improved the survival statistics in the last two decades. Spread of tumor cells widely throughout the abdominal cavity outside radiation or surgical fields, even in patients with apparently early disease, is the obvious reason. Studies are underway to assess the impact of long-term postoperative adjuvant chemotherapy with L-phenylalanine mustard, an alkylating agent effective in patients with advanced disease, in early stages of ovarian cancer following surgery and or x-irradiation. The search is on for more effective drugs, or combinations of drugs, that could subsequently serve as more effective adjuvant treatments. In carcinoma of the uterine cervix, chemotherapy as an adjunct to surgery and/or radiotherapy in patients with localized, or locally inoperable disease has been poorly evaluated; little data are available and the value of many established drugs in patients with metastatic cervical cancer is undermined. Some recent evidence suggests the use of hydroxyurea, a drug that by itself is not effective in controlling tumor, may enhance the effect of radiotherapy in patients with Stage II disease. Uterine fundal cancer is often successfully treated by surgery alone. The data for the use of pre- or postoperative radiotherapy are open to considerable question. While the relative nontoxic progesterone compounds are effective in a small but significant fraction of patients with advanced uterine cancer, no properly designed clinical trial has truly evaluated their role as postoperative adjuncts in patients who have resectable tumor but a definite high risk of recurrence. Systemic chemotherapy has been rarely used with any consistency against this tumor but, even so, some chemotherapeutic leads, such as the use of adriamycin, are worthy of exploration. The absence of useful information on systemic treatment of gynecologic malignancies can be traced to the excessive rigid compartmentalization of medical practice. Only recently have investigators of all persuasions begun to explore and exploit some of the therapeutic opportunities, which have been available for some time.