Concurrent Chemoradiotherapy in Locally Advanced Carcinoma of the Uterine Cervix Preliminary Results of Phases III Prospective Randomized Trial.

Abstract

A prospective, randomized phase III, clinical trial was performed to assess treatment related acute toxicity, early response and survival difference, between a monthly 5-FU cisplatin, and a weekly cisplatin group alone, for concurrent chemoradiotherapy in the locally advanced uterine cervical carcinoma patients. MATERIALS AND METGODS: Between March 1998 and March 2000, 35 patients, with locally advanced (FIGO stage IIB to IVA) cervical carcinoma, were studied, but 5 patients were excluded inform the analysis due to their refusal of treatment. The patients were randomly assigned to 'monthly 5-FU cisplatin' (arm I), or 'weekly cisplatin' (arm II), groups. The patients of arm I received 5-FU cisplatin (5-FU 1,000 mg/m2/day cisplatin 20 mg/m2/day, IV continuous infusion, for 5 days, 3 cycles with 4-week intervals) with radiation therapy. Those of arm II received only cisplatin (cisplatin 30 mg/m2/day, IV bolus, 6 cycles with 1-week intervals) with radiation therapy. The radiation therapy consisted of external beam irradiation of 41.4~50.4 Gy/23~28 fractions, and high dose rate intracavitary treatments, delivering a dose of 30~35 Gy to point A in 6~7 fractions. During intracavitary radiation, a parametrial boost was delivered for a point B dose of 60 Gy in the non-thickened side, and 65 Gy in the thickened side. Treatment related acute toxicities were assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. The response to treatment, and survival, were analyzed. The median follow-up period was 19 months. The FIGO stage distributions of arm I (n=16) and arm II (n=14) were as follows; IIB 10, IIIA 1, IIIB 4, IVA 1 in arm I, 12, 0, 1 and 1 in arm II respectively. The compliance of both arms were 80.0% and 93.3%, respectively (p=0.37). During radiation therapy, the incidences of leukopenia, greater than RTOG grade 2, were 25.0%, 14.3%, respectively. There were no patients with gastrointestinal or genitourinary toxicity greater than RTOG grade 2. The complete response rates at 3 months, following radiation therapy, were 87.5% and 92.9% respectively. Two-year disease free survival rates were 81.3%, 85.7%, respectively, for each arms. There was no significant difference in response to treatment, or patterns of failure, between the monthly FP and weekly cisplatin arms. Although there were no statistically significant differences, the patients of the weekly cisplatin arm had better compliance. More patients, and a longer follow up, are needed for improved evaluation of the regimen.