Concurrent Chemoradiotherapy in Locally Advanced Carcinoma of The Uterine Cervix : A Phase I/II Prospective Study

Kang, One Chul; Choi, Eun Kyung; Chung, Weon Kuu; Kim, Jong Hoon; Chang, Hyesook; Kim, Yong Man; Kim, Young Tak; Nam, Joo Hyun; Mok, Jung Eun; Lee, Moo Song

Abstract

PURPOSE: Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix.
METHODS
AND MATERIALS: From May 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/m2/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/m2/day intravenous bolus for 3 days, day 1-3, 29-31) administered starting on day 1 of RT.
RESULTS
The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol; The 5-year actuarial and disease-free survival rate were 52% and 64%, respectively. The 5-year actuarial survival for stage IIB and III+IVA patients were 58% and 36%, respectively. The 5-year disease-free survival rate for stage IIB andIII+IVA patients were 71% and 46%, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9% (19/68): local failure in 5.9% (4/68), distant metastasis in 10.3% (7/68) and both in 11.8% (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment, the complete response rate was 78% (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths.
CONCLUSION
Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.