Advances in the management of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in adult women. The most easily identifiable riskfactor is a strong family history of either ovarian or breast cancer; that may indicate the presence of an inherited germ-line mutation in either BRCA-1 or BRCA-2. Common symptoms, such as abdominal bloating and early satiety, indicate more advanced disease, involving the upper abdomen and present in approximately 70% of patients at the time of diagnosis. Physical examination often reveals the presence of a pelvic mass, which is best evaluated by transvaginal ultrasound (TVU) for confirmation. Exploratory laparotomy is required for histologic confirmation, staging and tumor debulking and should be performed by a surgeon trained in these aspects of ovarian cancer management. Patients with early-stage disease, limited to the ovary or pelvis (stages I and II, respectively), have survival in the 80-95% range, whereas the survival of patients with disease involving the upper abdomen or beyond (stages III and IV, respectively) is 10-30%. Because of the propensity of EOC to spread beyond the confines of the ovary, the majority of patients will require postoperative chemotherapy in an attempt to eradicate residual disease. For selected patients with early-stage disease, confined to the ovary, such as those with well-differentiated, completely encapsulated tumors (e.g., stage IA, grade 1), no further treatment is necessary in view of excellent survival after surgery alone. For patients with higher-risk early-stage disease (e.g., those with pelvic extension, capsular rupture or involvement, positive washings, ascites or high-grade lesions) and for patients with advanced-stage disease (stages III and IV), postoperative combination chemotherapy with a taxane and platinum combination is the standard of care. Such treatment is capable of inducing responses in > 70% of patients with residual EOC and is also capable of prolonging both disease-free and overall survival. Unfortunately, despite an initial response to chemotherapy in the majority of patients, relapse is afrequent problem and is often detected by a rise in the serum tumor marker CA-125 in the absence of symptoms or signs of disease by physical examination or radiographic studies. In such cases, a hormonal maneuver is oftentimes considered in order to avoid the toxic effects of chemotherapy when the patient is asymptomatic and the goal of treatment is largely palliation, although eventually the development of clinical progression mandates the institution of second-line chemotherapy. If the treatment-free interval is > 6 months from the completion of first-line treatment, rechallenge with platinum-based chemotherapy is a reasonable first step. For those patients who develop resistance to second-line platinum or who have difficulty tolerating this agent, multiple other options are available for relapse management, including liposomal doxorubicin, topotecan, gemcitabine and etoposide per os. Eventually the disease becomes resistant to multiple chemotherapy agents, and reorienting management toward supportive care and pain control is necessary. Ongoing efforts to identify more effective multiagent first-line regimens, to develop more effective strategies for early detection and to incorporate agents with novel mechanisms of action, such as antiangiogenesis compounds, hold promise.