Association of ABCC2 genotype with efficacy of first-line FOLFIRI in Japanese patients with advanced colorectal cancer.
Summary of "Association of ABCC2 genotype with efficacy of first-line FOLFIRI in Japanese patients with advanced colorectal cancer."
This exploratory retrospective study examined the effects of polymorphisms in transporter genes related to irinotecan pharmacokinetics and those in genes related to irinotecan pharmacodynamics on the efficacy of first-line combination chemotherapy with irinotecan, 5-fluorouracil, and folinic acid (leucovorin) (FOLFIRI) in Japanese patients with advanced colorectal cancer. All patients harbored UDP-glucuronosyltransferase (UGT) 1A1*1/*1, *1/*6, or *1/*28 genotypes, which are associated with similar irinotecan pharmacokinetics and responses to FOLFIRI. Genetic polymorphisms were analyzed by direct sequencing. Overall response rate and median progression-free survival in total 61 patients were 43% and 7.5 months, respectively. The overall response rate was higher in patients with CC genotype at -24 in ATP-binding cassette, subfamily C, and member 2 (ABCC2) than in the others (P=0.0313). Median progression-free survival was the longest in patients with CC at -24 in ABCC2, followed by those with CT and TT (P=0.00910). A clear gene-dose effect was seen between -24C>T and median progression-free survival. All other polymorphisms tested were not related to the efficacy of FOLFIRI. The efficacy of first-line FOLFIRI is related to -24C>T in ABCC2 in Japanese patients with advanced colorectal cancer. We thus found that -24C>T polymorphism in ABCC2 gene was significantly associated with the efficacy of first-line FOLFIRI.
Department of Medical Oncology, International Medical Center-Comprehensive Cancer Center, Saitama Medical University.
This article was published in the following journal.
Name: Drug metabolism and pharmacokinetics
Medical and Biotech [MESH] Definitions
Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.
L Cells (cell Line)
A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS.
The relative equivalency in the efficacy of different modes of treatment of a disease, most often used to compare the efficacy of different pharmaceuticals to treat a given disease.
Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS.
Swiss 3t3 Cells
A cell line established in 1962 from disaggregated Swiss albino mouse embryos. This fibroblast cell line is extremely popular in research.
PURPOSE: Differences in efficacy and toxicity between UDP-glucuronosyltransferase (UGT) 1A1*1/*1 and *1/*6 or *1/*28 genotypes remain unclear in Japanese patients. METHODS: Patients with advanced colo...
Irinotecan and infusional 5-fluorouracil-based chemotherapy (FOLFIRI) plus bevacizumab (FOLFIRI-B) is one of the most effective treatments of advanced colorectal cancer (CRC). However, this schedule i...
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