Concurrent chemotherapy and hypofractionated radiation therapy in cervix cancer patients with stage IIIB disease and bilateral parametrial involvement: a phase I/II study

Abstract

Purpose/Objective: Stage IIIB cervix cancer patients with bilateral parametrial involvement have a poor prognosis with low survival rates. In an effort to improve the poor outcome of these patients, we initiated in 1996 a prospective, Phase I/II trial of concomitant chemotherapy with cisplatin and 5-fluorouracil (5-FU) and hypofractionated twice-a-day radiation therapy. This program was based on the encouraging results obtained in the treatment of bladder cancer using similar regimen. The purpose of this study is to evaluate the results of treatment (toxicity, survival and pattern of failure) of this novel approach in patients with stage IIIB disease and bilateral parametrial involvement. Materials/Methods: Between March 1996 and July 1998, 34 previously untreated patients (median age: 43 years) with FIGO stage IIIB with bilateral parametrial involvement, squamous cell cervical cancer entered the study. Initial evaluation included complete blood work, a chest radiograph and a computed tomographic scan. Hemoglobin level was kept at or higher than 110 g/L. After the inclusion of the first 14 patients, the study was put on hold for 6 months and the patients were carefully observed. Once the toxicity was found acceptable, the remaining 20 patients entered the study. External beam radiation therapy (EBRT) was delivered twice a day, with at least a 6-hour interval, 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 BID. Thus, the final dose to the pelvis was 40 Gy. Low dose rate brachytherapy (35 Gy to point A) was delivered on day 29. Chemotherapy was administered on days 1 to 3, 15 to 17, 45 to 47 and 59 to 61 and consisted of cisplatin 15 mg/m2 and 5-FU 400 mg/m2. No patient has been lost to follow up. Results: Treatments were well tolerated and only one patient did not receive all chemotherapy cycles. None of the patients developed hematological toxicity grade 3–4. No Grade 3–4 acute GI or GU toxicities were seen and all patients completed the EBRT regimen as planned. Late Grade 3–4 GI or GU toxicity was seen in 4 (11.7%) and 1 (3%) patient, respectively. Another patient presented with intestinal obstruction 34 months post treatment requiring surgical intervention. No disease was found at time of laparotomy but the patient devoloped a fulminant septicemia and expired in the post-operative period. At a median follow-up time of 60 months (range: 7–84 months), 19 patients remain alive. The 3- and 5-year overall survival rates were 66.4% and 56.2%, respectively. Initial recurrence was confined to the pelvis only in 8 patients (23.5%), to distant site only in 3 patients (8.8%) and to both pelvic and distant site in 3 patients (8.8%). Conclusions: This protocol comprising concomitant chemotherapy with 5-FU and cisplatin and high dose BID hypofractionated split course radiation therapy has been associated with moderate toxicity and a survival that exceeds that previously reported for this high risk population.