Ovarian cancer, Part II: Treatment

The death rate from epithelial ovarian cancer has only slightly decreased in the past decade. In contrast, there have been dramatic improvements in the treatment of germ cell tumors of the ovary and the majority of patients even with advanced disease is now cured because of the development of effective platinum-based combination chemotherapy. Unfortunately, most patients with ovarian cancer have the epithelial histologic type, and only one third of these patients can be cured with standard approaches. It has recently been shown that a subset of patients with early stage ovarian cancer has a greater than 90% cure rate without chemotherapy. Consequently, a major focus of current research is to develop effective screening modalities in order to diagnose epithelial tumors when they are still confined to the ovaries and pelvis. Currently, three fourths of patients are diagnosed at the time the disease has spread throughout the peritoneal cavity, and the standard approach has been cytoreductive surgery followed by combination chemotherapy. The two-drug combination of carboplatin plus cyclophosphamide has now become the treatment of choice, although it is equally effective as and less toxic than a regimen of cisplatin plus cyclophosphamide. In addition, Taxol has been identified as an extremely active agent against this disease, and new Taxol-containing combinations are under clinical investigation. Clinical trials are also in progress with hexamethylmelamine and ifosfamide combinations as well as with more dose-intense regimens based on considerable retrospective evidence that survival is correlated with the dose intensity of platinum compounds. New agents such as WR2721, IL-3, and IL-1 alpha are undergoing clinical evaluation to determine whether the toxicities of platinum compounds can be decreased and lead to further exploitation of the dose response relationship. After induction chemotherapy, approximately 50% of patients will be in a clinical complete remission. Unfortunately, 30% to 50% of these patients will have recurrent disease; clinical trials are currently in progress to determine whether any form of therapy following the initial induction regimen can prevent or delay recurrences. Based on laboratory investigations in relevant models of human ovarian cancer, clinical trials are also in progress with novel new agents that may be capable of reversing drug resistance to platinum compounds and alkylating agents. For patients with germ cell tumors of the ovary, platinum-based combination chemotherapy has produced the same dramatic effects as in testicular cancer. Clinical trials are now focused on retaining therapeutic efficacy but decreasing the toxicity of treatment in these tumors that frequently affect women in their reproductive ages.