Concurrent chemotherapy and hypofractionated twice-daily radiotherapy in cervical cancer patients with stage IIIB disease and bilateral parametrial involvement: A phase I-II study

Stage IIIB cervical cancer patients with bilateral parametrial involvement have a poor prognosis with low survival rates. In an effort to improve outcome of these patients, we initiated a prospective, Phase I-II trial of concomitant chemotherapy with cisplatin and 5-fluorouracil and hypofractionated twice-daily radiotherapy. This program was initiated on the basis of the encouraging results obtained in the treatment of bladder cancer using a similar regimen. The purpose of this study was to evaluate the results of treatment (toxicity, survival, and patterns of failure) using this novel approach. A total of 34 patients with Stage IIIB squamous cell cervical cancer and bilateral parametrial involvement entered the study. After inclusion of the first 14 patients, the study was put on hold for 6 months, and the patients were carefully observed. Once the toxicity level was found acceptable, the remaining 20 patients entered the study. External beam radiotherapy was delivered twice daily on Days 1 and 3, 15 and 17, 45 and 47, and 59 and 61. The whole pelvis was treated each treatment day at a dose of 2.5 Gy b.i.d. Low-dose-rate brachytherapy (35 Gy to Point A) was delivered on Day 29. Chemotherapy was administered on Days 1–3, 15–17, 45–47, and 59–61 and consisted of cisplatin 15 mg/m 2 and 5-fluorouracil 400 mg/m 2. The treatments were well tolerated. None of the patients developed Grade 3-4 acute toxicity. Late Grade 3-4 GI or GU toxicity was seen in 4 (11.7%) and 1 (3%) patient, respectively. At a median follow-up of 60 months, 18 patients were alive. The 3-year and 5-year overall survival rate was 76% and 59%, respectively. This protocol, comprising concomitant chemotherapy and twice-daily hypofractionated split-course radiotherapy was associated with moderate toxicity and a survival that exceeds that previously reported for this high-risk population.