Induction of pathologic complete response by long-term neoadjuvant chemotherapy for gastric cancer: Early results of a randomized phase II study—A COMPASS trial.

Abstract

71 Background: Prognosis for stage III gastric cancer was not satisfactory even by D2 gastrectomy followed by S-1 adjuvant chemotherapy. Neoadjuvant chemotherapy will be another promising approach to improve the survival as demonstrated in some European trials, however, optimal duration and regimen have not been clarified yet. Methods: This trial compared efficacy of neoadjuvant chemotherapy using two and four courses of SC regimen; S-1 (80 mg/m2 for 21 days with 1 week rest) / cisplatin (60 mg/m2 at day 8), or PC regimen; paclitaxel / cisplatin (80 mg/m2 and 30 mg/m2, respectively at days 1, 8, and 15 with 1 week rest), by a two by two factorial design for stage II schirrhous / junctional tumors, stage III, or resectable stage IV. The primary endpoint was 3-year OS. Key secondary endpoints included pathological / clinical response, R0 resection, and adverse events. Sample size was set at 60 to 80 to achieve 10% improvement of 3-year OS by four courses or by PC with approximately 80% probability of the correct selection. Results: Between Oct 2009 and July 2011, 83 patients were assigned to arm A (2 courses of SC, n=21), arm B (4 courses of SC, n=20), arm C (2 courses of PC, n=21), and arm D (4 courses of PC, n=21). Clinical response (arm A/B/C/D) was 29%/40%/33%/24%. R0 resection (arm A/B/C/D) was 76%/75%/57%/76%. Pathological response (arm A/B/C/D), defined as tumor regression more than two third in the primary tumor, was 43%/40%/29%/38%. Pathological complete response (arm A/B/C/D) was 0%/10%/0%/10%. Major grade 3/4 toxicities (arm A/B/C/D) were anemia (14%/15%/0%/28.6%), neutropenia (10%/15%/14%/33%), nausea (0%/10%/5%/5%), and appetite loss (5%/10%/0%/5%). No surgical mortality was observed. Grade 3 morbidity classified by Clavien-Dindo was leakage in 5% (arm A), pancreatic fistula in 5% (arm C), and postoperative hemorrhage in 5% (arm B). Conclusions: This randomized phase II study suggested that pathological complete response could be induced by long-term neoadjuvant chemotherapy without increase of toxicities regardless of SC or PC regimen. Clinical trial information: UMIN000002595.