High-dose radiotherapy (60 Gy) with oral UFT/folinic acid and escalating doses of oxaliplatin in patients with non-resectable locally advanced rectal cancer (LARC): A phase I trial

Consensus is that patients with locally advanced rectal cancer (LARC) should receive long-term chemoradiotherapy (CRT) before surgery. With the intent to offer the patients intensified concomitant chemotherapy (CT) to improve outcome and to assess tolerability and toxicity of oxaliplatin (Ox) a phase I trial of high dose pelvic radiotherapy (RT), fixed dose of oral UFT/l-leucovorin and increasing doses of weekly Ox were performed.Pelvic RT with 48.6 Gy/27 fractions was given to the primary tumour and the regional lymph nodes and a concurrent boost of 5.4 Gy/27 fractions with a final boost of 6 Gy/3 fractions was given to the gross tumour volume (GTV) (60 Gy/30 fractions). Concurrent with RT patients received a daily dose of UFT 300 mg/m(2) plus fixed dose l-leucovorin 22.5 mg 5/7 days and increasing weekly doses of Ox with 10 mg/m(2)/week from a start dose of 30 mg/m(2)/week to a maximum of 60 mg/m(2)/week. In addition, before and after CRT the patients received one course of TEGAFOX (UFT 300 mg/m(2) with l/leucovorin 22.5 mg Days 1-14 and Ox 130 mg/m(2) given on Day 1). Surgery was planned at least six weeks after the completion of the CRT.From May 2005 to March 2009, 18 patients with LARC (16 primary, two recurrent) were included in this phase I trial. Toxicity was low with only 5-17% grade 3-4 toxicity. Fifteen patients (83%) were operated (14 R0 resection and 1 R1 resection) after completion of CRT. Five (33%) patients had a pathological complete response (ypCR). When ypCR was combined with yp few residual cells, the rate was 60%. Thirteen patients are still alive December 2011.Preoperative high-dose RT and concomitant UFT with increasing doses of Ox up to 60 mg/m(2)/week was feasible with low toxicity, high ypCR rates and promising OS in patients with non-resectable LARC.