P-0039 Irinotecan as a Second/Third Line Chemotherapy in Gastric Cancer Patients who Failed S-1-Based Treatment

Abstract

IntroductionUnresectable/metastatic gastric cancer patients have been treated with S-1 or S-1/CDDP combination in Japan. More recently, evidence has evolved that a second line treatment with irinotecan is superior in terms of survival time to the best supportive care among patients who failed a first line treatment. Efficacy of the second line after failing S-1 remains unknown. UGT1A1 genotyping is known to predict some of the adverse reactions. MethodsA phase II trial was conducted to evaluate the efficacy and safety of intravenous administration of irinotecan at 100 mg/m2 on days 1, 7, 14 every 4 weeks. Patients who failed treatment with a S-1 containing regimen were eligible. Another line of treatment was allowed before entering onto this study. All patients were to undergo genotyping of UGT1A1*6, *27 and *28, and only those with wild type gene and those heterozygous for either *6 or *28 were rendered eligible. The primary endpoint was response rate, assessed in accordance with the RECIST v1.1. A Simon optimal 2-stage design was adopted assuming unacceptable and acceptable response rates of 4% and 20% respectively, and 5% type I error and 20% type II error rates. Required sample size was 27 patients. Treatment-related toxicities were assessed according to the CTC-AE v3.0. ResultsForty-one patients underwent genotyping and 5 patients were excluded because of the inadequate genotype. Six other patients failed to receive irinotecan due to rapid disease progression prior to initiation of the treatment etc. Of the 30 patients who received treatment, 21 received irinotecan as the second line and 9 as the third line treatment. The median number of the 4-week treatment administered was 3 cycles. One CR, 3 PRs, 14 SDs and 6 PDs were recorded for the overall response rate of 13% and disease control rate of 60%, including 6 patients who failed to undergo formal evaluation by the imaging studies. Six of 7 patients who was heterozygous for UGT1A1*6 had either significant tumor shrinkage or stable disease. Grade III/IV toxicities included neutropenia (30%), anorexia (23%), leucopenia (17%), diarrhea (17%), anemia (13%), fatigue (13%), vomiting (10%) and thrombocytopenia (3.3%). Median survival time of all patients was 284 days, 342 days for the second line and 218 days for the third line treatment. ConclusionIrinotecan as a single agent was modestly active in the second/third line setting for advanced gastric cancer after failing S-1, with the response rate of 13% and disease control rate of 60%.