Progress in the Management of Gynecologic Cancer (2007)

This issue of the Journal of Clinical Oncology is dedicated to recent advances in the management of gynecologic cancers, with special reference to epithelial ovarian cancer. Improvement in the survival of patients with ovarian cancer has been slow but steady over the past three decades. Although the combination of intravenous (IV) taxane and platinum chemotherapy has improved survival in newly diagnosed patients with advanced disease, most are still not cured. More recently, three randomized trials have demonstrated that intraperitoneal (IP) administration of cisplatin confers an additional survival advantage compared with systemic chemotherapy in newly diagnosed patients with optimally debulked, stage III epithelial ovarian cancer. One of these studies used a regimen of IV paclitaxel on day 1, IP cisplatin on day 2, and IP paclitaxel on day 8, yielding a 16-month prolongation of median overall survival compared with the control arm of IV paclitaxel and cisplatin therapy. However, a substantial number of patients (58%) could not complete this regimen due to toxicities including catheter infection and blockage, febrile neutropenia, and neuropathy. The article by Rao et al discusses IP therapy in detail and reviews strategies to reduce the toxicity and further improve the efficacy of this approach. In this regard, the use of IP carboplatin instead of cisplatin, the use of lower doses of IP cisplatin, and the inclusion of bevacizumab into first-line IP therapy are approaches that are currently being investigated. Although IP therapy has now been embraced by many physicians as a reasonable strategy in the management of selected patients with newly diagnosed epithelial ovarian cancer, we must be careful not to extrapolate to populations in which efficacy has not been demonstrated. Such patients include those with stage IV disease, those with suboptimally debulked stage III tumors, those with high-risk early-stage disease, or those with recurrent disease. Furthermore, some patients with optimally debulked, stage III disease might be poor candidates for IP therapy due to comorbid conditions such as pre-existing neuropathy, renal disease, or extensive bowel adhesions. The treatment of patients with newly diagnosed ovarian cancer involves both surgical debulking and chemotherapy administration. Our gynecologic oncology colleagues have contributed a great deal to the initial treatment of patients with this disease, as discussed in the review by Fader et al. Achieving an optimal cytoreduction, currently defined as having no residual lesions larger than 1 cm in diameter, is associated with improved survival. Whether the ability to debulk simply selects for patients who are more responsive to postoperative chemotherapy, or whether debulking itself is therapeutically useful, is a question that will most likely never be answered. Fader et al discusses the important role of surgery in this disease and also reviews the proper place for secondary cytoreductive procedures in the management of recurrence. It is likely that further improvements in the outcome of patients with advanced ovarian cancer will not be based solely on traditional cytotoxic chemotherapy approaches. The recent demonstration that triple-drug combinations are no better than the paclitaxel and carboplatin doublet is a case in point. In recognition of this fact, we present three articles in this issue discussing immunologic approaches and novel strategies designed to target the angiogenesis pathway. These authors discuss exciting developments in their respective areas, including randomized trials such as Gynecologic Oncology Group (GOG) 218, which is designed to explore the role of bevacizumab in the first-line and maintenance setting. Single-agent bevacizumab has also been shown to induce responses in patients with recurrent ovarian cancer, although enthusiasm for this approach has been tempered by the recent demonstration of an 11% incidence of bowel perforation with this agent. It has been suggested that the number of prior cytotoxic regimens and the presence of bowel obstruction might predispose to this complication, although our ability to identify high-risk patients requires further investigation. In addition to antiangiogenic drugs, inhibitors of novel targets such as poly-ADP ribose polymerase hold a great deal of promise in patients with relapsed disease who harbor either BRCA-1 or BRCA-2 germline mutations. Not all ovarian cancers are associated with a poor prognosis. Within the epithelial category, early-stage disease is often curable with surgery alone, or with surgery followed by adjuvant chemotherapy. Trope et al discuss the management of early-stage disease and the selection of appropriate patients for adjuvant chemotherapy. Prevention of malignant transformation is the most definitive strategy for managing epithelial ovarian cancer, and Kauff et al review the role of risk reduction salpingooophorectomy in patients with BRCA-1 or BRCA-2 germline mutations. Borderline ovarian tumors are an interesting category of epithelial ovarian tumors that do not invade, are typically early stage and chemotherapy resistant, and generally have a good prognosis. These neoplasms are reviewed by Cadron et al, 16 and a case is made for more conservative surgery in selected young women who wish to preserve fertility. It is important to note that a subset of borderline tumors can behave aggressively, with a higher chance of relapse and transformation into low grade invasive serous carcinoma. Such borderline tumors are often characterized by the presJOURNAL OF CLINICAL ONCOLOGY O V E R V I E W VOLUME 25 NUMBER 20 JULY 1