A phase i study of IV doxorubicin plus intraperitoneal (IP) paclitaxel and IV or IP cisplatin in endometrial cancer patients at high risk for peritoneal failure (GOG 9920): An NRG Oncology/Gynecologic Oncology Group study

Objective To determine the maximum tolerated dose (MTD) of a modified paclitaxel/doxorubicin/cisplatin (TAP) regimen which incorporated intraperitoneal (IP) paclitaxel or IP paclitaxel/cisplatin in advanced endometrial cancer. Methods Patients (pts) with FIGO (1998) Stage IIIA/IIIC with positive cytologic washings/ascites, adnexa, or serosa or Stage IV (intraperitoneal disease spread), histologically confirmed endometrial cancer were eligible. The study was designed as a phase I, 3 + 3 dose escalation study evaluating 5 dose levels (DL). All pts received cycles 1-2 with IV TAP, and cycles 3-6 with IV/IP therapy, on a 21 day schedule. Adverse events were evaluated on cycles 3-4 for dose limiting toxicity (DLT) and dose escalation decisions. Results Twenty-one pts were enrolled, of which 17 were evaluable for DLT. Most pts had Stage IV disease (76%) and serous/clear cell histology (59%). The MTD was determined to be DL 3 (cycles 3-6 including paclitaxel 90 mg/m² IP, doxorubicin 45 mg/m² IV, cisplatin 50 mg/m²). Three DLT events occurred and were related to grades 3-4 metabolic toxicities. There was one grade 2 sensory neuropathy event and myelosupression was tolerable without the use of G-CSF. 88% of evaluable pts completed 6 cycles of therapy. With a median follow-up of 22 months, 46% of patients remain progression-free at 2 years. Conclusion We described an IV/IP based modification of a standard TAP regimen in endometrial cancer. Based on the high rate of completing 6 cycles of therapy, low rates of neuropathy, and promising PFS, further study of IP therapy in endometrial cancer is warranted.