Characteristics of early-onset hematotoxicity of sunitinib in Japanese patients with renal cell carcinoma

Purpose: To identify the characteristics of early-onset hematotoxicity of sunitinib in Japanese renal cell carcinoma (RCC) patients.

Material and Methods: Seventy-nine patients were treated with sunitinib as 6-week cycles of “4-week on 2-week off” schedule. To evaluate early-onset hematotoxicity, we compared patients with dose reduction during the first cycle (dose-reduced group, n=57) and those who maintained the initial dose (dose-maintained group, n=22). ABCG2 and flt-3 genotypes were analyzed for association between hematotoxicity and reported gene polymorphisms.

Results: Mean relative dose intensity (RDI) was similar in two groups during the first two weeks of dosing in the first cycle, but was significantly lower in dose-reduced group during the last two weeks. Lymphocytopenia, thrombocytopenia, and increased aspartate aminotransferase were observed in dose-reduced group within the first two weeks. Genetic analysis indicated significantly higher frequency of flt-3 738T/C polymorphism in dose-reduced group, but no significant difference in ABCG2 421C/A polymorphism.

Conclusion: This study showed a high incidence of sunitinib-induced hematotoxicity in Japanese RCC patients, many of whom need dose adjustment during the first cycle. Further studies should verify whether dose adjustment based on early-onset thrombocytopenia prolongs sunitinib treatment.