SAMIT: Preliminary safety data from a 2x2 factorial randomized phase III trial to investigate weekly paclitaxel (PTX) followed by oral fluoropyrimidines (FPs) versus FPs alone as adjuvant chemotherapy in patients (pts) with gastric cancer

Background: Recently, S1 has become a standard adjuvant chemotherapy for localized gastric cancer in Japan with no comparison among FPs so far. PTX is one of key drugs in gastric cancer especially for those with peritoneal metastases, for which serosal invasion is a major risk. SAMIT is an ongoing randomised phase III trial of adjuvant FPs (S1 or UFT) ± PTX in pts with SE or SI gastric adenocarcinoma. Methods: Pts received either A: UFT 267 mg/m2/day for 4w, every 4w x6; B: S1 80 mg/m2/day for 2w, every 3w x 8; C: paclitaxel 80 mg/m2 Day 1, 8 for the first 3w x1, Day 1, 8, 15 every 4w x2, followed by UFT 267 mg/m2/day for 4w, every 4w x3; or D: paclitaxel as in C, followed by S1 80 mg/m2/day for 2w, every 3w x4. The duration of treatment was amended from 24w to 48w by prolonging the part of FPs according to the results of ACTS-GC in 2007. Primary endpoint is disease-free survival and total number of patients was calculated to be 1480 where 90% power for superiority of C+D group and non-inferiority of UFT with 88% power in the upper equivalence margin of 1.25. The Independent Data Monitoring Committee undertook a review of the first 976 pts at the first interim analysis, and we present the preliminary safety data. Results: Between August 2004 and September 2009, 1,538 pts were accrued from 232 institutes, and 1495 pts were randomized. The pts who required dose reduction or skip between the first to third courses were 32%, 33%, 22%, and 27%; in the fourth to sixth courses were 18%, 20%, 18%, and 28% for A, B, C, and D, respectively. The compliance of UFT or S1 between the fourth to sixth courses were 76%, 86%, 81%, and 85% for A, B, C, and D, respectively. Grade 3/4 hematological toxicities were 0.8%, 0.4%, 1.6%, and 3.4%; grade 3/4 non-hematological toxicities were 7.3%, 7.2%, 2.4%, and 8.9% for A, B, C, and D, respectively. There was no treatment-related death. Conclusions: Preliminary safety data indicate comparable compliance; different but acceptable rates of complications in the 4 arms. The second interim analysis is currently undertaken and the final results will be formally assessed in 2012.