A Phase I Trial of Oxaliplatin, Irinotecan, and S-1 Combination Therapy

Background. OX-IRIS is a new combination therapy of oxaliplatin, irinotecan, and S-1 for unresectable pancreatic ductal adenocarcinoma (PDAC), which may be beneficial because S-1 is administered orally and continuous infusion of 5-fluorouracil (5-FU) is not needed. Methods. Patients who had not received prior therapy for unresectable PDAC were enrolled. Adenocarcinoma or adenosquamous histology was required. Oxaliplatin and irinotecan were administered on days 1 and 15; S-1 was administered orally twice a day on days 1-14, followed by 14 days of rest (one cycle). Primary endpoints were dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). Secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results. In level 0 (oxaliplatin, 85 mg/[m.sup.2]; irinotecan, 100 mg/[m.sup.2]; S-1, 80 mg/[m.sup.2]), two of five patients experienced DLT. In level -1 (oxaliplatin, 65 mg/[m.sup.2]; irinotecan, 100 mg/[m.sup.2]; S-1, 80 mg/[m.sup.2]), DLT could not be evaluated in two of eight patients because one cycle was not completed; one of the remaining six patients experienced DLT. Anemia, thrombocytopenia, fatigue, nausea, anorexia, diarrhea, and peripheral sensory neuropathy were seen frequently in levels 0 and -1. ORR was 30% in levels 0 and -1. Median progression-free survival and median overall survival were 4.1 months (95% confidence interval [CI], 0.0-8.9 months) and 13.7 months (95% CI, 4.8-22.6 months), respectively. Conclusion. MTD of OX-IRIS therapy was estimated to be level 0, and the recommended dose (RD) for future trial was level -1. Key Words. Pancreatic cancer * Combination therapy * Oxaliplatin * Irinotecan * S-1