Predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype in small cell lung cancer patients treated with chemotherapy.

PURPOSE: Multiple drug resistance limits the efficacy of numerous cytotoxic drugs used in the treatment of small cell lung cancer (SCLC). The drug efflux protein ATP-binding cassette transporter B1 (ABCB1) has an important role in this process, and its gene variability may affect chemotherapy outcomes. PATIENTS AND METHODS: This study aimed to evaluate the associations between ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype with progression-free survival (PFS) and overall survival (OS) in 177 SCLC patients treated with cisplatin-etoposide or cyclophosphamide-epirubicin-vincristine chemotherapy. To determine the ABCB1 genotype, allelic specific TaqMan(®) probes were used in a RT-PCR .
RESULTS: Patients carrying the G2677T/A TT + TA + AA genotypes (24 %) or the C3435T CT + TT genotypes (72 %) or the 2677T/A-3435T haplotype (40 %) had a longer PFS (Cox regression, P = 0.052, 0.037 and 0.037, respectively); these associations persisted also in multivariate analyses (Cox regression, P = 0.028, 0.037 and 0.030, respectively). Moreover, patients with the C3435T CT + TT genotypes had a longer OS both in univariate and multivariate analysis (Cox regression, P = 0.022 and 0.028, respectively). A trend toward longer OS was noted for the 2677T/A-3435T haplotype (Cox regression, P = 0.051), but its independent value was not confirmed (Cox regression, P = 0.071).
CONCLUSIONS: Our study reported a possible predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype for longer PFS and OS in Caucasian SCLC patients treated with chemotherapy. However, to be implemented into routine clinical practice, ABCB1 polymorphisms require further validation.