The optimal frequency of follow-up examinations is unknown, but in those patients who have completed chemotherapy and who are in clinical remission it is reasonable to perform a pelvic examination and to obtain a CA125 every-3-months for 1 to 2 years. An elevated CA 125 (> 35 U/mL) can provide lead time of approximately 3 months in detecting recurrent disease. A rising CA 125 can prompt the performance of a CT scan. The role of PET scanning in this setting has not been defined. A rising CA 125 in the absence of changes on physical examination or CT scan in a patient in initial remission poses a dilemma. At present, additional cytotoxic therapy is not recommended based on a rising CA 125 alone. As more effective salvage therapy becomes available, serum markers such as CA 125 may have greater utility. In patients whose disease was never found to be metastatic to the chest or who never had a pleural effusion, chest radiograph surveillance is not mandatory. In the absence of a rising CA125, follow-up CT or MRI scans should be used with discretion, perhaps 6 to 12 months after the completion of chemotherapy, and then again a year later.

Intravenous Second-line Therapy in Patients With Recurrent or Persistent Advanced Epithelial Ovarian Cancer
The overall prognosis is unfavorable for patients who do not achieve a complete remission with induction chemotherapy or who relapse after an initial response. Responses to second-line therapy can, however, be clinically beneficial. The frequency of a response to second-line therapy depends on both the nature of the prior response to initial therapy and the duration of remission. In patients who achieve a complete remission on a platinum-based induction regimen and have a disease-free interval of greater than 6 months, second-line treatment with a platinum complex has approximately a 30% response rate.-314-316 Patients can be retreated with either cisplatin or carboplatin. However, because of its more favorable toxicity profile, carboplatin is the drug of choice for patients who relapse after responding to a platinum-based induction regimen. In contrast, if patients do not achieve a remission on a platinum-based regimen or have a very short response duration, retreatment with a platinum-based regimen is unlikely to be beneficial, and such patients should be encouraged to enter experimental clinical trials.

As noted above, the current treatment of choice for patients with previously untreated ovarian cancer is the combination of carboplatin plus paclitaxel. Successful retreatment with paclitaxel is similar to that described above for platinum compounds. Patients who have responded to initial paclitaxel-based chemotherapy have a significant probability of responding to paclitaxel, that is dependent upon the length of response. There is no evidence that retreatment with a combination of paclitaxel plus carboplatin is superior to using these agents sequentially in patients with recurrent disease. However, many investigators do recommend that combination chemotherapy be used as part of reinduction for patients who have a disease-free interval that extends beyond 18 months. In patients who become resistant to paclitaxel and platinum compounds, a wide variety of second-line agents have been shown to have activity, including topotecan, gemcitabine, liposome-encapsulated doxorubicin, oral etoposide, and vinorelbine. All of these second-line agents have a comparable degree of activity with partial response rates of approximately 20%. Few formal comparisons have been performed among these drugs. Pegylated liposomal doxorubicin (PLD) has been compared to topotecan in a Phase III study. Similar response rates (19.7% vs 17.0%) and overall survival times (60 weeks vs 57 weeks) were observed for the entire group of patients with recurrent disease. PLD was more active than topotecan in the subset of women with platinum-sensitive disease, producing improved progression-free survival (29 weeks vs 23 weeks, p = .037) and overall survival (108 vs 71 weeks, p = .008). Selection of the appropriate agent for an individual patient is based upon prior toxicity, expected toxicities of the second-line agent, patient preference for intravenous versus oral administration, and quality of life considerations. It appears the older second-line agents, such as ifosfamide and hexamethylmelamine, have less clinical activity than do newer agents in patients whose tumors have become resistant to paclitaxel and platinum-based chemotherapy. Traditionally, second line agents have been used individually and sequentially, but two recent studies suggest that a combination of cisplatin and gemcitabine may exert synergistic effects, producing response rates of 38% and 70% with responses that have been maintained for 3-5 months.

High-dose Chemotherapy and Stem Cell Transplantation
The use of high-dose chemotherapy and either autologous bone marrow transplantation (ABMT) or peripheral stem cell support is being tested in patients with advanced ovarian cancer. In one trial of high-dose mitoxantrone, carboplatin and cyclophosphamide with stem cell support, 89% of patients responded with clinical complete responses in 88% of platinum-sensitive and 47% of platinum-resistant cases. Median progression free survival was 10.1 months for platinum sensitive disease and 5.1 months for platinum resistant disease. In another retrospective analysis of 35 patients treated with high-dose melphalan and stem cell support, 9 of 12 patients with evaluable residual disease had a measurable response. The morbidity of this approach is high, and the survival after this approach in a Phase II trial has been similar to the survival following second-line paclitaxel. A prospective randomized clinical trial of a combination very high-dose chemotherapy supported with autologous bone marrow transplantation versus standard-dose chemotherapy with paclitaxel and carboplatin was initiated by the GOG, but the trial was discontinued because of poor accrual. Transplantation earlier in the course of disease may have a greater impact. One recent study of 96 patients, many of whom were in clinical CR (43%) or PR (34%), produced 6-year survival of 37%. For patients who received transplantation for remission consolidation, the 6-year survival was 53% and the progression free survival was 29%.