Combined chemo- and radiotherapy vs. radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum

Purpose: In a randomized study in primarily inextirpable rectal cancer, conventional radiotherapy to reduce the tumor mass was compared with combined chemotherapy and radiotherapy. Methods and Materials: The combined treatment (CRT) was given every other week, four times, during a 7-week period. The drugs used were methotrexate, 5-fluorouracil in bolus injection followed by continuous infusion and leucovorin rescue. Radiotherapy (RT) was given simultaneously with five 2-Gy fractions in 3 days to a dose of 10 Gy to a total dose in the four courses of 40 Gy. This regimen was compared with radiotherapy in 2-Gy fractions to a total dose of 46 Gy in the radiotherapy group. Surgery was performed 3-4 weeks after finished treatment. Seventy patients were included between November 1988 and August 1996; 36 patients were allocated to RT and 34 to CRT. Results: Twenty-five (74%) of the patients in the CRT group underwent a locally radical resection with 20 (59%) patients without any known metastases. The corresponding figures in the RT group were 23 (64%) and 18 (50%), respectively. Among the patients who underwent any tumor resection, 5/29 (17%) in the CRT group and 12/27 (44%, p=0.05) in the RT group have had a local recurrence. After a locally radical resection, the corresponding figures are 4% and 35% (p=0.02), respectively. Local disease-free survival was significantly superior in the CRT group (66% at 5 years) compared with the RT group (38%, p=0.03 log-rank test). Five-year survival was 29% (9 patients) in the CRT group and 18% (6 patients) in the RT group, a nonsignificant difference (p=0.3). Five patients in the RT group did not complete planned treatment, mainly due to the appearance of metastatic disease. In this group toxicity was usually of Grade 0-1. In the experimental group, the toxicity usually was Grade 2 or higher, and 6 patients did not manage to fulfill the planned treatment due to toxicity. Conclusion: In this study, with fewer included patients than intended, resectability rates were high in both groups. The addition of chemotherapy to radiotherapy significantly improved local control rates, but no statistically significant difference was found in survival between the groups. The acute toxicity after CRT was higher than after RT alone, but manageable