AIM: We performed a phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer based on UDP-glucuronosyltransferase (UGT) 1A1 polymorphism. PATIENTS AND METHODS: A total of 28 patients were enrolled. The dose of irinotecan was 150 mg/m(2) for patients with the *1/*1 wild-type genotype, and 70 mg/m(2) for those with the *1/*28 mutated genotype. The primary end-point was the response rate (RR); secondary end-points were safety, time to treatment failure (TTF), and overall survival (OS). RESULTS: In 28 patients total, genotype was wild-type in 22 and mutated in six. The RR was *1/*1 (22.7%; wild-type) vs. *1/*28 (16.7%; mutated); the median TTF was 5 months vs. 4.5 months, and the median OS was 13 months vs. 17.5 months, respectively. None of these differences were significant. Toxicities of grade 3 or higher were neutropenia (9.0% vs. 0%, respectively) and diarrhea (13.6% vs. 0%, respectively). CONCLUSION: This genotype-oriented therapy was effective and safe, and thus appears useful for patients who have complications or advanced age.
AIM: We performed a phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer based on UDP-glucuronosyltransferase (UGT) 1A1 polymorphism. PATIENTS AND METHODS: A total of 28 patients were enrolled. The dose of irinotecan was 150 mg/m(2) for patients with the *1/*1 wild-type genotype, and 70 mg/m(2) for those with the *1/*28 mutated genotype. The primary end-point was the response rate (RR); secondary end-points were safety, time to treatment failure (TTF), and overall survival (OS). RESULTS: In 28 patients total, genotype was wild-type in 22 and mutated in six. The RR was *1/*1 (22.7%; wild-type) vs. *1/*28 (16.7%; mutated); the median TTF was 5 months vs. 4.5 months, and the median OS was 13 months vs. 17.5 months, respectively. None of these differences were significant. Toxicities of grade 3 or higher were neutropenia (9.0% vs. 0%, respectively) and diarrhea (13.6% vs. 0%, respectively). CONCLUSION: This genotype-oriented therapy was effective and safe, and thus appears useful for patients who have complications or advanced age.
Authors: Matthew P Goetz; Heidi A McKean; Joel M Reid; Sumithra J Mandrekar; Angelina D Tan; Mary A Kuffel; Stephanie L Safgren; Renee M McGovern; Richard M Goldberg; Axel A Grothey; Robert McWilliams; Charles Erlichman; Matthew M Ames Journal: Invest New Drugs Date: 2013-10-10 Impact factor: 3.850
Authors: Carlo Lancia; Jakob K Anninga; Matthew R Sydes; Cristian Spitoni; Jeremy Whelan; Pancras C W Hogendoorn; Hans Gelderblom; Marta Fiocco Journal: Cancer Chemother Pharmacol Date: 2019-03-16 Impact factor: 3.333