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Background: It is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and toxicity of irinotecan monotherapy in advanced gastric cancer (AGC). We investigated the association between clinical outcomes (efficacy and safety) and UGT1A1 status in patients who received irinotecan monotherapy., Methods: We evaluated AGC patients who received irinotecan monotherapy between January 2011 and December 2017. Efficacy was assessed according to overall survival (OS) and progression-free survival (PFS). Toxicity was graded using the Common Toxicity Criteria for Adverse Events (version 4.0)., Results: A total of 100 patients were evaluated (62 and 38 patients with UGT1A1 WT and SH, respectively). In the WT and SH groups, the irinotecan dose was reduced in 19 (30.6%) and 18 (47.2%) patients (p = 0.135), respectively; treatment was delayed due to adverse events (AEs) in 19 (30.6%) and 13 (34.2%) patients (p = 0.826), respectively; the median PFS was 3.15 and 3.25 months (HR, 0.734; 95% CI 0.465-1.158; p = 0.184), respectively; and the median OS was 10.4 and 7.26 months (HR, 1.137; 95% CI 0.752-1.721; p = 0.543), respectively. Severe hematological AEs (Grade ≥ 3) were significantly more frequent in the SH group than in the WT group (63% vs. 36%; p = 0.008), while severe non-hematological AEs was not significantly different (16.0% vs. 6.5%; p = 0.173)., Conclusion: There was no significant difference in the efficacy of irinotecan monotherapy between UGT1A1 WT and UGT1A1 SH, but UGT1A1 SH was associated with a high frequency of severe hematological toxicity.

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/m2; irinotecan, 100 mg/m2; S‐1, 80 mg/m2), 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/m2; irinotecan, 100 mg/m2; S‐1, 80 mg/m2), two of five patients experienced DLT. In level −1 (oxaliplatin, 65 mg/m2; irinotecan, 100 mg/m2; S‐1, 80 mg/m2), 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. [ABSTRACT FROM AUTHOR]

Background. In Japan, a study comparing the effectiveness and safety of irinotecan plus S-1 (IRIS) with those of a combination of 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as second-line treatment in patients with advanced or recurrent colorectal cancer demonstrated that IRIS was non-inferior to FOLFIRI. We previously reported that IRIS is also effective as first-line treatment. Patients and methods. Eligibility criteria included inoperable recurrent colorectal cancer with a confirmed diagnosis of adenocarcinoma, age ≥20 years, and no history of prior chemotherapy. S-1 (40-60 mg twice daily) was given orally on Days 1 to 14, and irinotecan (100 mg/m2) and bevacizumab (5 mg/kg) were given intravenously on Days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS). Results. A total of 52 eligible patients were enrolled from October 2007 through March 2009. In safety analysis, the incidences of grade 3 or 4 adverse reactions were as follows: neutropenia, 27%; hypertension, 21%; and diarrhea, 17%. The overall response rate was 57.7%. Median progression-free survival was 16.7 months. Conclusion. IRIS plus bevacizumab is a well-tolerated, highly effective chemotherapeutic regimen that is easy to administer. [ABSTRACT FROM AUTHOR]