A phase I study with an expanded cohort to assess feasibility of intravenous docetaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with previously untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study.

OBJECTIVE: To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) docetaxel, intraperitoneal (IP) carboplatin and IP paclitaxel in women with stage II-IV untreated ovarian, fallopian tube or primary peritoneal carcinoma. METHODS: Patients received docetaxel (55-75 mg/m(2)) IV and carboplatin (AUC 5-7) IP on day 1 and paclitaxel 60 mg/m(2) IP on day 8. A standard 3+3 design was used in the dose escalation phase. A 2-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. RESULTS: The MTD determined during the dose escalation phase was day 1 docetaxel 75 mg/m(2) IV, carboplatin AUC 6 IP and day 8 IP paclitaxel 60 mg/m(2). Forty-six patients were enrolled in the feasibility portion at this dose level. Six were unevaluable. Fifteen evaluable patients had dose-limiting toxicities (DLTs) within the first four cycles. These DLTs were prolonged neutropenia (2), neutropenic fever (7), grade 4 thrombocytopenia (1), grade 4 dehydration (1), grade 3 infection (2), grade 3 oral mucositis (1) and pulmonary embolism (1). CONCLUSIONS: Docetaxel 75 mg/m(2) IV, carboplatin AUC 6 IP administered on day 1, and paclitaxel 60 mg/m(2) IP administered on day 8, is the MTD when considering one cycle of treatment but was not feasible over four cycles due to bone marrow toxicity. We recommend reduction of carboplatin to AUC 5 should this regimen be considered for treatment in women with newly diagnosed advanced ovarian cancer.