Irinotecan

Studies on the effects of third-line chemotherapy (CT) in advanced gastric cancer (GC) patients are still scarce. The aim of this study was to evaluate the efficacy and safety of the modified 5-fluorouracil, leucovorin, and irinotecan (mFOLFIRI) regimen as a third-line CT in metastatic GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane. After failure of first- and second-line therapies, 42 patients received third-line FOLFIRI (180 mg/m² irinotecan and 400 mg/m² leucovorin administered concomitantly as a 90-minute intravenous (IV) infusion on day 1, followed by a 400 mg/m² 5-fluorouracil IV bolus then 2600 mg/m² continuous infusion over 46 hours), between January 2009 and December 2015. FOLFIRI was administered for a median of 6 cycles (range 4-12 cycles). Eight patients achieved partial response, while 13 patients showed stable disease, resulting in the overall response rate (ORR) of 19% and disease control rate (DCR) of 50%. The most frequent grade 3-4 hematological and non-hematological toxicities were neutropenia (14.2%) and diarrhea (7.1%). The median progression-free survival (PFS) and overall survival (OS) from the start of third-line CT were 3.8 months (95% confidence interval [CI], 3.0-4.5) and 6.8 months (95% CI, 5.6-7.9), respectively. According to the multivariate analysis, two factors were independently predictive of the poor OS: >2 regions of metastasis (relative risk [RR], 2.6; 95% CI, 1.3-5.4) and a high level of carcinoembryonic antigen [CEA] (RR, 3.4; 95% CI, 1.6-7.4). In conclusion, FOLFIRI was well tolerated as third-line CT and showed promising PFS and OS in advanced GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane.

Purpose Irinotecan plus cisplatin (IP) improved survival over etoposide plus cisplatin (EP) in Japanese patients with extensive-stage small-cell lung cancer (E-SCLC). To confirm those results and discern the potential role of population-related pharmacogenomics (PG) in outcomes, we conducted a large randomized trial of identical design to the Japanese trial in North American patients with E-SCLC. Patients and Methods Patients were randomly assigned to IP (irinotecan 60 mg/m2 on days 1, 8, and 15; cisplatin 60 mg/m2 day 1, every 4 weeks) or EP (etoposide 100 mg/m2 on days 1 through 3; cisplatin 80 mg/m2 day 1, every 3 weeks). Blood specimens for genomic DNA analysis were collected before random assignment in 169 patients. Results Of 671 patients, 651 were eligible (324 and 327 patients in the IP and EP arms, respectively). Response rates with IP and EP were 60% and 57%, respectively (P = .56). Median progression-free survival for IP and EP was 5.8 and 5.2 months, respectively (P = .0...

We describe an important number of confirmed hypersensitivity reactions to leucovorin during a one-year period. Leucovorin can be included in FOLFOX/FOLFIRI regimes and be a hidden allergen (making doctors falsely think the reaction was caused by oxaliplatin or irinotecan). We show how patients reacting to leucovorin may also react to l-isomer calcium folinate and we explore the issue of cross-reactivity with oral folinate. We believe protocols studying FOLFOX/FOLFIRI hypersensitivity reactions should be undergone by drug allergy experts and include systematic skin testing and drug provocation testing with folinic acid, to avoid infra-diagnosis and its resulting risks. Moreover, we report the first intravenous rapid desensitization to leucovorin in a reactive patient (confirmed by drug provocation testing).

Irinotecan is a pro-drug of SN-38 primarily used for the treatment of colorectal cancer and used for other type of cancers either alone or combined with other chemotherapeutic drugs. A major dose limiting side effect of irinotecan is the late-onset diarrhea. The mechanism of irinotecan-induced diarrhea is not entirely understood and current approaches to prevent diarrhea are not quite effective in many patients. Recent evidences showed that gut microflora plays an important role in irinotecan-induced diarrhea. In this paper, we summarized the gut toxicity of irinotecan, the possible mechanism, the role of bacterial translocation, and clinical perspectives. The goal is to facilitate a better understanding of the role of bacterial translocation in regulation of irinotecan disposition and toxicity, and the potential implications in patients.