In Japan, gemcitabine based chemotherapy has been a standard regimen as one of the first-line treatment for unresectable pancreatic cancer. FOLFIRINOX was introduced in the second-line treatment for the gemcitabine-refractory pancreatic cancer of patients with an ECOG performance status score of 0 or 1. However, FOLFIRINOX requires close monitoring and must be limited to patients with good performance status because of significant toxicity. Further FOLFIRINOX requires a central veins port, and a trouble such as the port infection may occur. Therefore, it is difficult to administer FOLFIRINOX as second-line treatment. The first time in the world, we introduced IRISOX which substituted S-1 for fluorouracil and leucovorin in the second-line treatment. We aimed to evaluate the tolerance, safety, and clinical efficacy of IRISOX in the second-line treatment for the gemcitabine-refractory pancreatic cancer in a phase 1 study.
The primary objective was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IRISOX. The study was designed in accordance with a standard 3 + 3 method. Patients received 2-week cycles of treatment. Irinotecan was administered as an intravenous infusion at 100, 120, or 150 mg/m2 on day 1, S-1 was administered orally at 80 mg/m2 twice daily for 7 days, and oxaliplatin was administered as an intravenous infusion at 85 mg/m2 on day 1.
Among the 12 patients enrolled, dose-limiting toxicity was observed in a patient at level 1 (irinotecan 100 mg/ m2 on day 1, S-1 80 mg/m2 twice daily, and oxaliplatin 85 mg/m2 on day 1) , and in two patients at level 2 (irinotecan 120 mg/ m2 on day 1, S-1 80 mg/m2 twice daily, and oxaliplatin 85 mg/m2 on day 1). The MTD was established as level 2. The RD was established as level 1. The most common grade 3-4 toxicity was neutropenia (33.3 %). The overall response rate was 9.0 %. The overall disease control rate was 45.4 %.
Based on the present results, the RD was determined as level 1 (irinotecan 100 mg/ m2 on day 1, S-1 80 mg/m2 twice daily, and oxaliplatin 85 mg/m2 on day 1). IRISOX was well tolerated and showed antitumor efficacy in the second-line treatment for the gemcitabine-refractory pancreatic cancer in a phase 1 study.
Clinical trial identification
Legal entity responsible for the study
Kitasato University School of Medicine, Japan.
Has not received any funding.
All authors have declared no conflicts of interest.