A prospective phase I/II trial of capecitabine with escalating mitomycin C and oxaliplatin in patients with advanced or metastatic esophageal carcinoma

Abstract

15555 Background: In preclinical studies, mitomycin C (MMC) was found to upregulate thymidine phophorylase thereby enhancing cytotoxic activity of capecitabine. Moreover, capecitabine shows promising activity in combination with oxaliplatin in patients with esophageal cancer. Therefore, we conducted a prospective phase I/II trial of the combination of capecitabine, MMC, and oxaliplatin in patients with unresectable advanced esophageal carcinoma. Methods: Capecitabine (2,000 mg/m2, bid, d1–14) and oxaliplatin (100 mg/m2, q3 weeks) were kept constant while MMC was escalated: 6–10 mg/m2, q 6 weeks. Results: 25 pts (3 F, 22 M) received 171 cycles (median 7). Median age was 64 years (41–70). Dose-limiting toxicities were grade 4 thrombocytopenia or grade 4 neutropenia. No patients died from adverse events related drug toxicity. The maximal tolerable dose (MTD) for MMC was 6 mg/m2, q6 weeks. Partial response was seen in 10/25 pts (40%), stable disease in 11/25 pts (44%) and progressive disease in 4/25 pts (16%). Median progression-free survival was 8.9 months (95% CI, 6.2–11.6), and median overall survival was 13.3 months (95% CI, 10.8–15.8). Conclusion: The triple regimen of capecitabine, MMC and oxaliplatin is well tolerated and shows substantial clinical activity in unresectable esophageal carcinoma. The high survival rates suggest the need for prospective randomized studies of this treatment strategy. Updated results will be presented. No significant financial relationships to disclose.