Phase I study of weekly PTX+ DDP, and postoperative radiotherapy for early cervical cancer in Chinese women

Abstract

Objective To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly PTX and DDP concurrent postoperative radiotherapy in Chinese women with high-and intermediate-risk early cervical cancer. Methods Women with high risks postoperative cervical carcinoma, ECOG≤2 were eligible. Pelvis RT (6/10 MV X-ray, 3DCRT 40 Gy/20f, para-metrial boost 10-20 Gy/5-10f) was followed by 2-4f brachytherapy applications (192Ir, 5 Gy/f). Concurrent weekly chemotherapy was started at DDP 20 mg/m2 and PTX 10 mg/m2 weekly, and escalated in three-patient cohorts according to 3+ 3 methods. Results 25 patients were enrolled and treated over seven doses levels until dose-limiting toxicity (DLT) was reached. Median age was 48 years (range, 34-66). All of patients finished RT in 7 weeks. Grade 3, 4 non-hematologic toxicities were diarrhea and observed in two patients (4 cycles, DLT) at level 7.Grade 3, 4 hematologic, principally leukopenia and neutropenia, and occurs late cycles. One grade 4 leukopenia and neutropenia was observed at dose level 6 but not seen in three additional patients. No one was delayed treatment time by concurrent chemotherapy.22 patients finished 6 cycles. Median follow-up is 59.5 months. Three patients have died of cancer metastasis and recurrence. One patient has died of respiratory failure. Conclusions Combination PTX and DDP administered concurrently with pelvic EBRT can be safely administered at the MTD of DDP 35 mg/m2 and PTX 30 mg/m2 weekly for six cycles in Chinese women with postoperative cervical cancer. Key words: Cervical neoplasms/chemoradiotherapy; Radiotherapy, three-dimensional conformal; Chemotherapy, PTX+ DDP; Phase Ⅰ study