Phase I-II trial of concomitant pre-operative hyperfractionated radiotherapy and gemcitabine for locally advanced rectal cancers

3678 Background: To determine the maximum tolerated dose (MTD) of gemcitabine when administered concomitantly with hyperfractionated radiotherapy (RT) preoperatively in patients with locally advanced rectal cancers and to investigate the mid-term efficacy of such a regimen. Methods: 37 patients with stages II-III tumors were enrolled. RT consisted in 50 Gy given in 2 daily fractions of 1.25 Gy in 4 weeks. The starting dose of Gemcitabine was 10 mg/m2/day (in a 30 min IV perfusion) twice weekly with planned escalation steps of 5 mg/m2/day. Main end-points for of the study were complete pathological tumor response, the rate of clear margin resection as well as actuarial locoregional control and disease-free survival. The median follow-up for all patients was 32 months (range: 10–51 months). Results: 2/4 patients presented with dose-limiting rectal toxicities at the level of 45 mg/m2 (severe acute proctitis requiring hospitalization in the immediate post-RT period). Thus, the gemcitabine biweekly dose of 40 ...