Discussion
tBendamustine-based, death, thymic carcinoma, prostatic small cell carcinoma
DRUG INTERACTIONS, SOLID TUMORS
After administering bendamustine orally to 18 patients with advanced solid tumors, FN (n = 1) and a decrease in platelet count (n = 2) were observed as DLT; however, no AEs led to death or discontinuation of orally-administered bendamustine. PR was obtained in one patient each with prostatic small cell carcinoma and thymic carcinoma. As two of six patients had PR at 75 mg/mAs shown in Table S2, the bioavailability of orally-administered bendamustine was sufficiently high, and the individual variability in PK parameters was generally similar to that of bendamustine injection. The tBendamustine-based regimens have been recommended in the NCCN guidelines [Bendamustine is rapidly eliminated from the blood, and mono-hydroxylated and di-hydroxylated bendamustine are primarily formed by rapid hydrolysis. A portion of the bendamustine is metabolized via CYP1A2 into demethylated bendamustine. Therefore, drug interactions with CYP1A2 inhibitors or inducers are unlikely because of the limited contribution of CYP1A2 to bendamustine metabolism. The effect of bendamustine exposure is not dependent on age, ethnicity, sex, or differences in liver and kidney function [The MTD, RD, and recommended treatment schedule were determined to be 75 mg/m