Characteristics of early-onset hematotoxicity of sunitinib in Japanese patients with renal cell carcinoma.
A high incidence of severe hematological adverse events during sunitinib treatment complicates decision making on dose and treatment cycle. We identified the characteristics of early-onset hematotoxicity of sunitinib in Japanese patients with renal cell carcinoma (RCC).



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 FLT3 genotypes were analyzed for association between hematotoxicity and reported gene polymorphisms.



Mean relative dose intensity (RDI) was similar in the two groups during the first 2 weeks of dosing in the first cycle, but was significantly lower in the dose-reduced group during the last 2 weeks. Lymphocytopenia and thrombocytopenia were observed in the dose-reduced group within the first 2 weeks. Genetic analysis indicated a significantly higher frequency of FLT3 738 T/C polymorphism in the dose-reduced group, but no significant difference in the ABCG2 421 C/A polymorphism.



This study showed a high incidence of sunitinib-induced hematotoxicity in Japanese patients with RCC, 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.
Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate, 020-8505, Japan. rekato@iwate-med.ac.jp.
Renpei
0000-0001-6089-7620
R
Kato
Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate, 020-8505, Japan.
Yoichiro
Y
Kato
Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate, 020-8505, Japan.
Tomohiko
T
Matsuura
Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate, 020-8505, Japan.
Mitsugu
M
Kanehira
Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate, 020-8505, Japan.
Ryo
R
Takata
Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate, 020-8505, Japan.
Wataru
W
Obara
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D000077210:Sunitinib
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
Asian population; Hematotoxicity; Renal cell carcinoma; Sunitinib