First-line therapy for ovarian carcinoma: what's next?
Based on results from large, randomized trials conducted over the last 25 years, the current standard of care for newly diagnosed advanced (FIGO stage III-IV) ovarian carcinoma is surgical bulk reduction followed by six cycles of paclitaxel plus carboplatin. This approach has resulted in an enhanced response rate and clinical complete response rate, an improved progression-free survival, an increase in survival, and more long-term survivors. Despite these results, the overall frequency of relapse and hence need for second-line therapy is 62%. Ongoing and future studies focus or will focus on four major themes: dose intensity through the use of intraperitoneal chemotherapy in selected patients, addition of a third cytotoxic agent to front line therapy, addition of a targeted or biologic agent to front-line therapy, and the development of effective maintenance or consolidation therapy. The current standard of care for patients who present with limited (FIGO stage I-II) ovarian carcinoma is the use of prognostic factors to classify the patient as at low risk or high risk for recurrence. High risk features include: grade 2 or 3 disease, disease on the surface of the ovary, disease outside the ovary, positive peritoneal cytology, or the presence of ascites. Any one high risk feature makes the patient high risk for recurrence. Patients at low risk require surgical resection only, whereas those at high risk for recurrence require adjuvant therapy. Ongoing studies evaluate the duration of therapy and the potential value of anti-angiogenic agents in those patients at high risk for recurrence. Future directions point to the evaluation of targeted or biologic agents in high risk patients. At present, there is no evidence that any approach constitutes an effective screening test. Studies of serum markers, transvaginal sonography, and serum proteomic profiles have failed to establish any of these techniques as an effective tool for early diagnosis. An overview of current management and its basis will be followed by a discussion of the rationale for both current and potential future trials.