Chemotherapy in ovarian carcinoma: present role and future prospects

Abstract

Epithelial carcinoma of the ovary is characterized by presentation at an advanced stage, spread primarily by an intraperitoneal (IP) route, and relative sensitivity to chemotherapy. An initial surgical approach is essential to proper staging of the disease process and to aggressive cytoreduction, which in turn improves response to chemotherapy and survival. The use of chemotherapy is the mainstay of definitive therapy after completion of the initial surgery. A large number of drugs have activity against the disease, with the most important single category of agents being the platinum compounds. Studies by the Gynecologic Oncology Group (GOG) document the superiority of cisplatin-based combination chemotherapy over single alkylating agents and combinations that do not include cisplatin. The current regimen of choice is a two-drug combination of cisplatin plus cyclophosphamide. Efforts to improve results further focus on enhancing dose intensity of the drug combination through either escalating intravenous (IV) doses or administering cisplatin via an IP route. Also offering an opportunity for further improvement of therapeutic results are three drugs identified as having activity in patients no longer candidates for cisplatin: carboplatin, ifosfamide, and taxol. Biologic agents, such as alpha-interferon, also have potential roles in future combination therapy. The management of patients with limited (stage I or II) disease is based on studies of the GOG and the Ovarian Cancer Study Group, which indicate that this population can be divided by prognostic factors into a group at low risk for recurrence and a group at high risk. Those at low risk require only surgery, whereas those at high risk should receive either IP radioactive chromic phosphate or systemic chemotherapy following surgery. The future prospects for additional improvement of results in all patients appear bright on the basis not only of studies of dose intensity and IP therapy but also of efforts directed at overcoming multidrug resistance and at devising noninvasive means of assessing disease status.