Abstract:

Objective To identify genetic polymorphisms ABCG2/FLT3/VEGFR2 related to the pharmacokinetics and pharmacodynamics of sunitinib that are associated with thrombocytopenia in Chinese patients with metastatic clearcell renal cell carcinoma（mcc-RCC） treated with sunitinib. Methods Eighty-two mccRCC patients treated with sunitinib were enrolled in this study. Genotype analyses were done before treatment and thrombocytopenia was recorded on the first three cycles of treatment. Genetic polymorphisms of ABCG2（rs2231137, rs2231142）, FLT3（rs1933437） and VEGFR2（rs2305948） were analyzed for a possible association with thrombocytopenia. Results Gene types of rs2231137, rs2231142, rs1933437 and rs2305948 were according to Hardy-Weinberg law. The rs2231142 CC genotype was associated with a lower risk for thrombocytopenia grade 3, 4 when compared with the AA／AC genotypes （25.0％ vs. 47.6％， P=0.034）. The rs1933437 TT genotype was associated with a higher risk for thrombocytopenia grade 3, 4 when compared with the CC／CT genotypes （48.7％ vs.25.6％, P=0.030）. No significant differences were detected in thrombocytopenia grade 3, 4 among rs2231137（34.9％ vs. 37.5％ vs. 42.9％，P=0.912） and rs2305948（31.7％ vs. 47.6％ vs.100％， P=0.177） genotype subgroups. Conclusion This study showed that the risk for thrombocytopenia was increased in the presence of the A allele genotype in ABCG2 421C／A， and C allele genotype of FLT3 738T/C has a protective effect against sunitinibinduced thrombocytopenia.