The study closed after a median follow-up of only 8.5 months, and an interim analysis showed a significant 7-month prolongation in median progression-free survival (28 versus 21 months) with 9 versus 3 months of consolidation paclitaxel. There was no difference in median overall survival and this study has not changed practice. The rate of disease progression increased significantly after maintenance therapy was discontinued, which suggested that long-term survival was not likely to be improved. It is improbable that a survival benefit will appear with longer follow-up, because patients assigned to three cycles were given the option of receiving an additional nine courses of paclitaxel after the study was discontinued (228). Another placebo-controlled, randomized trial using two formulations of paclitaxel is being conducted by the GOG.
Topotecan Four additional treatment courses of topotecan were administered to patients following six cycles of carboplatin and paclitaxel in two randomized trials, one conducted in Italy and the other in Germany (229,230). In the larger trial conducted in Germany, 1,059 evaluable patients were randomly assigned to six cycles of paclitaxel (175 mg/m2 over 3 hours) and carboplatin (AUC 5) with (537 patients) or without (522 patients) four additional cycles of topotecan (1.25 mg/m2 intravenous days 1 to 5 every 3 weeks) (230). In the Italian trial, 273 women were randomly assigned to receive four additional cycles (137 patients) of topotecan at a dose of 1 mg/m2 on days 1 to 5 every 3 weeks or no further chemotherapy (136 patients) (229). Preliminary reports suggest no significant differences in either progression-free or overall survival in patients who received four to six cycles of consolidation topotecan.
Cisplatin In a randomized clinical trial of intraperitoneal cisplatin for consolidation versus observation, there was no difference in survival between the treatment arms (231).
Biologic Therapies As noted above, the use of the monoclonal antibody (MonAb) bevacizumab with first-line carboplatin and paclitaxel chemotherapy followed by maintenance bevacizumab for a year was associated with a modest improvement in progression-free survival, (225,226). Patients and their physicians may consider maintenance therapy with bevacizumab as delivered in GOG 218 and ICON7. There are a number of ongoing trials addressing the role of oral angiogenesis inhibitors as maintenance therapy after completion of first-line therapy in women with advanced ovarian cancer.
Studies MonAbs directed toward CA125 (OvaRex) and toward the HMFG (human milk fat globulin) tumor–associated antigens were conducted (232–234). In a randomized, placebo-controlled trial of intravenous oregovomab (anti-CA125 MonAb) as maintenance therapy, Berek et al. reported that oregovomab did not demonstrate a survival advantage as a maintenance therapy (233). A randomized trial of an intraperitoneally administered yttrium-labeled antimucin (HMFG) MonAb versus placebo was not associated with an improved overall survival after a negative second-look laparoscopy (234).
Treatment Assessment Many patients who undergo optimal cytoreductive surgery and subsequent chemotherapy for epithelial ovarian cancer have no evidence of disease at the completion of treatment. Tumor markers and radiologic assessments are too insensitive to exclude the presence of subclinical disease. Historically, a second-look surgery was performed to evaluate these patients, but was abandoned, as there is no evidence of a meaningful benefit to patients (132,235– 244).