The limited effectiveness of currently available chemotherapy in the treatment of advanced esophageal cancer, and the poor survival achieved in locally advanced disease with combined chemoradiotherapy with or without surgery, have prompted the evaluation of new agents. Irinotecan (CPT-11, Camptosar) has promising single-agent activity in gastrointestinal cancers. In phase II evaluation of weekl...

PURPOSE The aim of this study was to determine the daily maximum tolerated dose (MTD) and the dose-limiting toxicity for the following administration schedules: oral irinotecan given over 14 days every 3 weeks (part I) and oral irinotecan administered concomitantly with capecitabine over 14 days every 3 weeks (part II). In total, 42 patients (17 male and 25 female) with solid tumors refractory ...

Irinotecan unexpectedly causes severe toxicity of leukopenia or diarrhea. Irinotecan is metabolized to form active SN-38, which is further conjugated and detoxified by UDP-glucuronosyltransferase (UGT) 1A1 enzyme. Genetic polymorphisms of the UGT1A1 would affect an interindividual variation of the toxicity by irinotecan via the alternation of bioavailability of SN-38. In this case-control study...

UNLABELLED PURPOSE To determine whether irinotecan plus oxaliplatin (IROX) is superior to irinotecan alone in patients with metastatic colorectal cancer (CRC) previously treated with single-agent fluoropyrimidines. PATIENTS AND METHODS A phase III, randomized, open-label, multicenter study of patients with metastatic or recurrent CRC that had progressed or recurred during or after adjuvant or f...

The prodrug irinotecan is an active agent for the treatment of advanced colorectal cancer and a number of other solid tumors. Irinotecan is converted in vivo to SN-38 (7-ethyl-10-hydroxy-camptothecin), the active metabolite that causes cell death, by human liver carboxylesterases. Previous studies suggest that human carboxylesterase 2 (CES2) is the key activating isoform. Although conversion of...

BACKGROUND Second-line irinotecan-based chemotherapy is commonly used in metastatic colorectal cancers after first-line oxaliplatin-based chemotherapy. No standard schedule of irinotecan has been established in this situation. PATIENTS AND METHODS Metastatic colorectal cancer patients included in the OPTIMOX1 phase III study received first-line oxaliplatin-based chemotherapy (FOLFOX). No seco...

Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC). This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated...

Irinotecan (CPT-11, Camptosar) is a semisynthetic water-soluble derivative of the plant alkaloid camptothecin. This review will focus on the potential use of irinotecan in combination with fluorouracil (5-FU) in the preoperative combined-modality treatment of advanced rectal cancer. The laboratory studies that define the mechanism of fluoropyrimidine- and camptothecin-mediated radiosensitizatio...

Green synthesis of mPEG–PLGA and nanoformulation for delivery irinotecan to colon cancer.

BACKGROUND PEP02 is a novel highly stable liposomal nanocarrier formulation of irinotecan. This randomized phase II study evaluated the efficacy and safety of single agent PEP02 compared with irinotecan or docetaxel in the second-line treatment of advanced oesophago-gastric (OG) cancer. PATIENTS AND METHODS Patients with locally advanced/metastatic disease who had failed one prior chemotherap...