A Pilot Clinical Trial of Surgical Adjuvant Treatment with High-Dose 6S-Leucovorin/5-Fluorouracil and Radiation Therapy for High-Risk Rectal Carcinoma

Abstract

Aims and background

The study was performed to evaluate the feasibility of combining leucovorin (LV) with 5-fluorouracil (5FU) and radiation therapy as adjuvant treatment for high-risk rectal carcinoma.

Methods

Twenty-five patients with histologically proven adenocarcinoma of the rectum, at high-risk of recurrence after potentially curative resection (T3 NO, T any N1-2; MO), received 5FU (370 mg/m²) and 6S-LV (100 mg/m²) on days 1-5, 4 and 8 weeks after surgery. On treatment day 64, radiotherapy on the pelvis (50 Gy) was initiated. Finally, three further courses of 5FU/LV were given at intervals of 4 weeks beginning 28 days after the completion of radiotherapy.

Results

The treatment was generally well tolerated. We observed only 2 cases of grade III toxicity (diarrhea) during the third cycle of chemotherapy. No severe complications were recorded following the use of radiotherapy. The mean overall 5FU dose intensity was 92%. After a median follow-up of 24 months, 4 patients had relapsed (liver, lung, and pelvis, 2 cases).

Conclusions

The association of LV to 5FU and radiation therapy seems to be feasible, with acceptable toxicity. The advantage of this combination, in terms of recurrence rate and survival with respect to 5FU/radiotherapy alone, will have to be evaluated in randomized trials.