Objective. Incorporating topotecan into standard platinum/taxane chem otherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplatin, followed by paclita xel and carboplatin, in newly diagnosed advanced ovarian cancer patients. Method s. Forty-five patients (median age, 56 years; range, 38-77 years) with stage I II/IV disease and GOG performance status < 2 were enrolled and received four cyc les of topotecan (1.0 mg/m2/day on days 1 to 3) and carboplatin (AUC 4 on day 1) , followed by four cycles of paclitaxel (175 mg/m2 via 3-h IV infusion on day 1 ) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete respon se (CR) underwent second-look laparotomy for determination of pathologic CR (PC R). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia , and for grade 3/4 nonhematologic toxicity. Results. Among 41 CA-125 evaluable patients, complete and partial responses were observed in 29 (70.7%) and 11 (26.8%) patients, r espectively. Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progressi on was 14 months and actuarial survival was 23 months. Neutropenia was the prima ry toxicity and cause of dose adjustments and delays, including two deaths. Conc lusion. The antitumor activity observed is comparable with other series, althoug h neutropenic complications were increased. Progression-free and actuarial surv ivals were slightly inferior. A Phase Ⅲtrial (GOG182) of sequential doublets in the reverse sequence is ongoing. Objective. Incorporating topotecan into standard platinum / taxane chemotherapy for advanced ovarian cancer has been complicated by myelosuppression. This study was sequential doublets of topotecan and carboplatin, followed by paclitaxel and carboplatin, in newly diagnosed advanced ovarian cancer patients. Method s. Forty -five patients (median age, 56 years; range, 38-77 years) with stage I II / IV disease and GOG performance status <2 were enrolled and received four cycled les of topotecan (1.0 mg / m2 / day on days 1 to 3) and carboplatin (AUC 4 on day 1) followed by four cycles of paclitaxel (175 mg / m2 via 3-h IV infusion on day 1) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete respon se (CR) underwent second-look laparotomy for determination of pathologic CR (PC R). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia, and for grade 3/4 nonhematologic t Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 (41%) in 28 evaluable patients, complete and partial responses were 29 (70.7%) and 11 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progressi on was 14 months and actuarial survival was 23 months. Neutropenia was the prima ry toxicity and cause of dose adjustments and delays, including two deaths. Conc lusion . The antitumor activity observed is comparable with other series, althoug h neutropenic complications were increased. Progression-free and actuarial survivals were slightly inferior. A Phase IIItrial (GOG182) of sequential doublets in the reverse sequence is ongoing.