Genetic Polymorphism of CYP3A5 in Advanced Non-Small-Cell Lung Cancer Patients Treated with Paclitaxel-Based Chemotherapy
Keywords:
Paclitaxel, chemotherapy, non-small-cell lung cancer, genetic polymorphism, CYP3A5Abstract
Paclitaxel, an anticancer drug, is recommended first-line therapy for patients with advanced
non-small-cell lung cancer. Genetic polymorphisms of Paclitaxel's metabolic pathway may affect
treatment outcomes and adverse events. The purpose of this study was to explore the prevalence of
CYP3A5 rs776746 and determine the association of genetic polymorphism and treatment outcomes
in Thai NSCLC treated with Paclitaxel-based chemotherapy. Among 49 patients, the prevalence of
CYP3A5*3 was 67.5%; the number of patients with CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3
were 4, 30 and 24 persons, or 6.9%, 51.7% and 41.4%, respectively. The response rate of patients with
*1/*1 and *1/*3 was 31%, while the response rate of patients with *3/*3 was 25%. The most common
adverse symptoms found in this study was peripheral neuropathy (69.4%). The other common adverse
events were anemia and neutropenia, at 65.3% and 42.8%, respectively. Grade 3 or 4 anemia were
found in 10.2% of patients and grade 3-4 neutropenia 8.2%. The incidence of grade 3 or 4 hematologic
toxicity among patients with CYP3A5*3/*3 was higher than CYP3A5*1 (25% vs 17.2%). This study
found that CYP3A5 polymorphism was not associated with treatment outcomes or adverse events in
Paclitaxel-based chemotherapy among Thai advanced-NSCLC patients. However, our study indicated
that NSCLC patients with a family history of cancer had significantly greater disease progression
(6.75 times; 95% CI=1.67-27.34, P = 0.005) compared with cases with no family history of
cancer
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