Phase II trial of preoperative chemoradiation with a hyperfractionated radiation boost in locally advanced rectal cancer.

Purpose: The purpose of this phase II study was to prospectively determine the efficacy of preoperative chemoradiation with a hyperfractionated (Hfx) RT boost to 61.8 Gy in locally advanced rectal cancer.

Methods: Eligibility stipulated that the primary lesion had to be either T4; or T3 and >4 cm or 40% of the bowel circumference. Radiation (RT) consisted of 45 Gy to the pelvis (1.8 Gy per fraction) followed by 1.2 Gy twice daily (to the gross tumor volume) to a total RT dose of 61.8 Gy. There was 5-FU infused at 1 g/m2/24 hours for 4 days during the 1st and 6th weeks of RT (concurrent with the Hfx boost). Surgical resection was planned 4 to 6 weeks later. Adjuvant chemotherapy (bolus 5-FU/leucovorin) was scheduled for 4 cycles at 28-day intervals.

Results: There were 22 patients, ages 22 to 81 years (median, 64) enrolled in the study. Of the 20 patients evaluable for response, 10 (50%) had evidence of clinical downstaging and 5 patients (25%) had > or =90% fibrosis in the resected specimen. With a median f/u of 40 months (7-158), the 4 years actuarial rate for all patients (n = 22) of OS was 64%, of DFS 62%, and of LC 84%. 3/21 patients (14%) had positive margins, all of whom developed a local failure (P < 0.001).

Conclusion: This regimen of high dose preoperative chemoRT with a Hfx RT boost (to 61.8 Gy) in patients with bulky, locally advanced rectal cancer results in clinical downstaging in half of the patients with significant fibrosis in the operative specimen.