A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with 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) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II-IV ovarian, fallopian tube, or primary peritoneal carcinoma.

METHODS

Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60 mg/m(2) on day 8. A standard 3+3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.

RESULTS

Patients were treated with paclitaxel 175 mg/m(2) IV and carboplatin IP from AUC 5-7 on day 1 and paclitaxel 60 mg/m(2) IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4 cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), >2 week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135 mg/m(2) IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4 cycles with one DLT (grade 3 hyponatremia).

CONCLUSIONS

Paclitaxel at 175 mg/m(2) IV, carboplatin AUC 6 IP day 1 and paclitaxel 60 mg/m(2) IP day 8 yield 18-56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.