Background:Determining the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of sorafenib (S) plus imatinib (IM) in castration-resistant prostate cancer (CRPC) patients.
Methods:Refractory CRPC patients were enrolled onto this 3+3 dose escalation designed study. Imatinib pharmacokinetics (PK) were determined on day 15, 4 h post dose with a validated LC-MS assay.
Results:Seventeen patients were enrolled; 10 evaluable (6 at 400 mg S qd with 300 mg IM qd (DL0) and 4 at 400 mg S bid with 300 mg IM qd (DL1)); inevaluable patients received < 1 cycle. The median age was 73 (57-89); median prostatic serum antigen was 284 ng ml(-1) (11.7-9027). Median number of prior non-hormonal therapies was 3 (1-12). Dose-limiting toxicities were diarrhoea and hand-foot syndrome. Maximum tolerated dose was 400 mg S and 300 mg IM both daily. No biochemical responses were observed. Two patients had stable disease by RECIST. Median time to progression was 2 months (1-5). Median OS was 6 months (1-30+) with 3/17 patients (17%) alive at 21 months median follow-up. Ten patients had PK data suggesting that S reduced IM clearance by 55%, resulting in 77% increased exposure (P=0.005; compared with historical data).
Conclusion:This is the first report showing that S+IM can be administered in CRPC at a dose of 400 mg S and 300 mg IM, daily.
Written by:
Nabhan C, Villines D, Valdez TV, Tolzien K, Lestingi TM, Bitran JD, Christner SM, Egorin MJ, Beumer JH. Are you the author?
Department of Medicine, Division of Hematology and Oncology, Advocate Lutheran General Hospital, Park Ridge, IL, USA.
Reference: Br J Cancer. 2012 Aug 7;107(4):592-7.
doi: 10.1038/bjc.2012.312
PubMed Abstract
PMID: 22805325
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