Concurrent carboplatin/5-fluorouracil and radiotherapy for recurrent cervical carcinoma

Background: Results of salvage therapy in patients with carcinoma of the uterine cervix recurrent after surgery have been dismal even when the disease was apparently confined to the pelvis. Concurrent chemoradiation is one of the several avenues being investigated to improve these results. Patients and methods: Thirty-five women with recurrent cervical carcinoma were enrolled in the trial. Twenty-eight patients (80%) had disease limited to the central pelvis (ten), lateral pelvis (fourteen) and vagina (four) and seven had paraortic metastases. Patients were treated with a combination of external radiotherapy (50-70 Gy) along with three cycles of 5-fluorouracil (1000 mg/m2/24-hour continuous infusion days 1-4) and carboplatin (75 mg/m2 in bolus days 14). Results: Treatment was well tolerated, with 30 patients (86%) completing the protocol as planned. Acute toxicity was severe but manageable; 11 patients (31%) experienced grades 3-4 acute toxicity. Late morbidity occurred in five patients (14%). Overall response rate was 74% (11 partial responses and 15 complete). After a median follow-up of 27 months (range 18- 90), 13 patients (37%) are alive without disease, 4 (11%) are alive with persistent disease and 18 (52%) are dead of their disease. Actuarial two-year survival rate for the series as a whole is 44% and three-year survival is 25%. Stage of the primary disease, site of recurrence, interval from the primary therapy to recurrence, lymph node involvement, ureterohydronephrosis at the time of recurrence and diameter of the relapse are the most significant factors for survival, while complete response is related to diameter and site of relapse and lymph node status at the time of relapse. Conclusion: The acceptable toxicity, high response rate and satisfying survival would suggest that concomitant carboplatin/5-fluorouracil and radiotherapy is a safe and tolerable treatment for recurrent cervical carcinoma. Further studies are needed to demonstrate an eventual survival benefit of this type of chemoradiation over standard radiotherapy alone and to identify the subsets of patients who in particular might benefit from this