A Phase I Trial of Oxaliplatin, Irinotecan, and S‐1 Combination Therapy (OX‐IRIS) as Chemotherapy for Unresectable Pancreatic Cancer (HGCSG 1403)

LESSONS LEARNED: Because S‐1 is orally administered, OX‐IRIS does not necessitate the continuous infusion of 5‐FU and is more convenient. The recommended dose of OX‐IRIS was determined to be level −1 (oxaliplatin, 65 mg/m(2); irinotecan, 100 mg/m(2); S‐1, 80 mg/m(2)), which has manageable safety and promising anticancer activities. 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(2); irinotecan, 100 mg/m(2); S‐1, 80 mg/m(2)), two of five patients experienced DLT. In level −1 (oxaliplatin, 65 mg/m(2); irinotecan, 100 mg/m(2); S‐1, 80 mg/m(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.