Final response data of a phase II study of capecitabine and oxaliplatin (CAPOX) in advanced adenocarcinoma of the small bowel or ampulla of Vater

Abstract

4538 Background: Small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC) are rare tumors. There is limited information regarding chemotherapy in advanced disease and no current standard of care. Methods: Patients with either metastatic or locally advanced unresectable SBA or AAC with adequate organ function, performance status (PS) ≤2 and measurable disease per RECIST were enrolled from 11/04 to 7/07. Prior use of 5-FU either as adjuvant therapy or as a radiosensitizer was allowed. CAPOX was administered as a 21 day cycle with oxaliplatin 130 mg/m2 IV on day 1 and capecitabine 750 mg/m2 PO BID days 1- 14. The planned sample size was 30 and the primary endpoint was overall response rate (ORR). Results: Thirty patients (12 AAC and 18 SBA) have been treated and 29 are evaluable for response. Patients had either locally advanced (5) or metastatic disease (25) and 5 had prior adjuvant 5-FU. The median age was 62 years (41–79); 40% females; 97% PS of 0–1. The median number of cycles administered was 5 (1 to 11); 4 patients remain on treatment. Common grade 3/4 toxicities included fatigue (7), neuropathy (2), granulocytopenia (3), vomiting (3), diarrhea (3), thrombocytopenia (2), and hypokalemia (2). Fifteen patients, 5 AAC and 10 SBA, had a confirmed response with an ORR of 52% (95% CI 33 to 71%); 11 patients had stable disease (SD). Six patients (20%) are currently without evidence of disease. Three patients with metastatic disease are alive in complete remission (CR), two following CAPOX alone and a third following consolidative radiation, at 31, 28, and 21 months, respectively. Three patients with locally advanced disease with SD or PR to CAPOX have since undergone surgery and are alive without evidence of disease at 8, 10, and 20 months. Median PFS is 9.8 m (95% CI 4.7 to 30+m). Twelve patients have died. With a median follow-up of 12.1 months, median overall survival is 20.3 m (95% CI 13 to 30+m). Conclusions: This prospective trial demonstrates that CAPOX delivered to good PS patients with advanced SBA or ACC is well tolerated and leads to the highest response rate and median survival ever reported from prospective trials in these tumor types. We believe, CAPOX should be considered the new standard regimen for advanced SBA and AAC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis