| Abstract: | A comprehensive research effort has been focused on ovarian cancer during the past decade and this research focus has resulted in substantial improvements in accurate staging and effective treatment. On the basis of prospectively performed clinical trials in well-staged early ovarian cancer patients, a subset can be identified in whom no further therapy is necessary. Consequently, these patients can be spared the toxicities associated with long-term use of adjuvant chemotherapy. For patients with advanced disease, cisplatin-based combination chemotherapy regimens have produced higher complete response rates, prolongation of disease-free survival, and, in several large studies, a statistically significant prolongation of overall survival. In addition, recent clinical and laboratory data has confirmed the importance of dose and dose intensity in the optimum management of patients with ovarian cancer, and preliminary results of high-dose regimens are encouraging. Unfortunately, high-dose cisplatin-based chemotherapy regimens are associated with increased toxicity. However, pharmacologic techniques to decrease toxicity have been proven effective in murine models and clinical trials in patients have recently been initiated. Furthermore, the development of new cisplatin analogs may also permit further dose escalations with decreased long-term toxicities. There are also new promising clinical approaches that may be useful in treatment of patients who are left with small volume residual disease. It seems that approximately 30% of these patients can achieve disease-free status with intraperitoneal cisplatin therapy. While these results need to be confirmed in larger prospective trials, they do suggest that some patients with residual disease can be salvaged with intraperitoneal chemotherapy. Our understanding of the biology of ovarian cancer has been greatly facilitated by the development of relevant experimental model systems. These model systems have been used to help unravel the mechanisms associated with broad cross-resistance that currently limits the effectiveness of combination chemotherapy. In addition, pharmacologic techniques have already been shown to be capable of reversing resistance both in vitro and in vivo and these exciting new approaches will be entering clinical trial in the not too distant future. Finally, biological agents have also shown marked efficacy in these model systems of human ovarian cancer.(ABSTRACT TRUNCATED AT 400 WORDS) |
