Phase I trial of concomitant chemoradiotherapy for cervical cancer and other advanced pelvic malignancies

Purpose. The aim of this study was to determine the feasibility and toxicity of concomitant hydroxyurea (HU) and escalating doses of 5-fluorouracil (5-FU) in locally advanced cervical cancer and other pelvic malignancies undergoing radiation therapy (RT). Methods. Treatment consisted of 5-FU, HU, and pelvic RT delivered in an alternate-week fashion. 5-FU was administered as a continuous intravenous infusion at a starting dose of 600 mg/m2/day and was escalated to 1000 mg/m2/day in cohorts of three patients. The HU dose was 500 mg twice daily. Chemoradiotherapy was administered on a 5-day cycle. Following a 9-day rest, the cycle was repeated until the completion of the pelvic RT. Results. Twenty-one patients (18 cervix, 1 bladder, 1 vagina, 1 ovary) were enrolled. 5-FU escalation to 1000 mg/m2/day was well tolerated. No patients developed grade 3-4 hematologic toxicity. Grade 2 leukopenia was noted in 3 patients (14.3%). Grade 3 mucositis, diarrhea, and dermatitis occurred in 10, 10, and 5% of patients, respectively. None of the 99 treatment cycles were delayed secondary to acute toxicity. The overall response rate in the 18 cervical cancer patients was 89% (78% complete, 11% partial). Conclusions. Concomitant continuous infusion 5-FU, twice daily HU, and pelvic RT delivered in an alternate-week fashion is well tolerated. Further study is necessary to evaluate the therapeutic efficacy of this regimen in patients with advanced cervical and other pelvic malignancies.