Neoadjuvant therapy of gastric cancer with cetuximab added to both irinotecan and cisplatin, followed by surgical resection and adjuvant chemoradiation

Abstract

e15552 Background: We previously demonstrated the efficacy of irinotecan (CPT) and cisplatin (Cis) combination therapy as neoadjuvant therapy for locally advanced gastric cancer [Newman E et al. J Gastrointest Surg. 2002.]. This trial was designed to add cetuximab (C) to both induction treatment and adjuvant chemoradiation (CRT) with bolus 5-FU/LV. Methods: Pts with untreated locally advanced (T3, T4 or N+) gastric/GE cancers were eligible. Neoadjuvant therapy consisted of Cis 25mg/m2 + CPT 75mg/m2 on d1,8 q21d x 4, C 400mg/m2 on d1, then 250mg/m2 qwk. Curative (R0) resection was performed 4–6 wks later. Adjuvant CRT with 5-FU/LV (425/20/m2 qd x 5 on wks 1,14,19; 400/20/m2 qd x 4 on wk 5, x 3 on wk 9) was given with C 250mg/m2 qwk. Results: Since 11/05, 21 pts [median age 59 (32–82); 9 Caucasian, 11 Asian, 1 Hispanic; 15 male, 20 PS 0–1] received neoadjuvant therapy. The most common toxicities were gr 3 neutropenia (38%), gr 2 rash (33%), gr 2 fatigue (29%); gr 4 included 1 pt each of diarrhea, neutropenia, & hypomagnesemia. 3 did not complete neoadjuvant therapy, due to gr 3 rash, diarrhea and GI bleeding (2 had gastrectomy; 1 lost to f/u). All 18 pts who completed neoadjuvant therapy were surgically explored. 4 had occult metastases, and went off study. 14 underwent R0 gastrectomy (see table); 8 were downstaged, 2 had stable disease, 4 were upstaged compared to the preoperative EUS. There was no postoperative mortality. Of 14 resected pts, 2 did not receive adjuvant therapy (prolonged postoperative recovery), 1 too early to assess, and 11 remaining receiving CRT. The most common toxicities for CRT were gr 3 nausea, gr 3 emesis, gr 2 and 3 fatigue, 3 pts each and 1 each of gr 4 neutropenia and thrombocytopenia. Among the 18 pts who completed neoadjuvant therapy, 5 died of disease, 1 is alive with disease, 12 remain NED with median f/u of 11.6mos (4.1–27.7mos). Conclusions: The addition of C to CPT/Cis as neoadjuvant therapy and to postoperative adjuvant CRT is well tolerated. The regimen induces a favorable pathologic response on the primary tumor. Ongoing evaluation includes K-ras mutation status on outcome and survival benefit. [Supported in part by a grant from BMS.] [Table: see text]