Phase I trial of the treatment of high-risk endometrial cancer with concurrent weekly paclitaxel and cisplatin and whole abdominal radiation therapy: A Gynecologic Oncology Group study

Objectives To determine the maximum tolerated dose (MTD) and feasibility of weekly cisplatin and paclitaxel chemotherapy administered concurrently with whole abdominal radiation therapy (WART) in women with high-risk endometrial cancer. Methods Following surgery, patients with stage III–IV endometrial cancer (any histology) or with stage I–II serous or clear cell histology, and with largest residual disease ≤2 cm were eligible for this phase I feasibility trial. Six weekly cycles of chemotherapy were administered with WART in dose level (DL) cohorts of 3 patients in a 3+3 design. Once the MTD was defined, a second, feasibility portion of the trial was conducted to assess for chronic toxicity. All patients were to be treated with 25 Gy to the abdomen and 50.2 Gy to the pelvis. Results Thirty-five patients were enrolled in the study, including 21 in the dose finding portion, and 14 in the feasibility portion of the trial. The initial DL tested was paclitaxel 10 mg/m 2 and cisplatin 20 mg/m 2 . The MTD identified was at DL3 using paclitaxel 20 mg/m 2 and cisplatin 25 mg/m 2 . The most common acute dose-limiting toxicities (DLT) were gastrointestinal and hematologic. The prescribed radiation therapy was successfully delivered to 32/35 patients. Twenty patients (6 phase I, 14 feasibility) were assessed at the MTD. No acute grade 4 toxicities, and two grade 3–4 chronic toxicities were observed in these patients. Treatment contributed to the deaths of 2 patients. Conclusion A regimen of cisplatin 25 mg/m 2 and paclitaxel 20 mg/m 2 weekly with WART was determined to be feasible, but is associated with moderate acute and chronic gastrointestinal toxicity.