e16107 Background: Sorafenib (SOR) is a multi-kinase inhibitor, targeting Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β. Interferon-α (IFN) is most commonly used for metastatic renal cell carcinoma (RCC) in Japan. In this phase I study, we investigated the safety profile, pharmacokinetics (PK), and tumor response of SOR/(recombinant)IFN combination in Japanese patients (pts) with RCC. Methods: After 2 weeks of IFN-alone treatment, a total of 18 pts (6 in each cohort) with unresectable/metastatic RCC received 28-day cycles of continuous SOR 200 (Cohort 1 [C1]) or (Cohorts 2 and 3 [C2 and C3]) 400 mg bid combined with intramuscular IFN 6 (C1 and C2) or 9 (C3) MIU three times a week (tiw). Objectives were safety/tolerability and recommended dose of SOR/IFN as primary, and tumor response and PK as secondary. Results: Pt characteristics were: median 64.5 y.o.; ECOG-PS 0:1, 14:4; prior anticancer therapy in 13 pts. All pts completed Cycle 1 and entered Cycle 2 or later cycles. At data cut-off (September 30, 2008), dose-limiting toxicities were reported in all cohorts, including G3 fatigue, G3 anorexia, and G3 skin disorders. Common drug-related grade 3/4 adverse events (AEs) included fatigue (50%), lipase increased (44%) and neutropenia (39%), all of which were reversible and manageable. AEs resulting in treatment discontinuation in Cycle 2 or later cycles were seen in 5 pts in Cohort 3. One death was reported in C1 at Cycle 18 due to gastrointestinal and intraabdominal hemorrhage. It seemed attributable to DIC accompanied by RCC. Five PR (1 in C1 and 4 in C3) and 11 SD (4 in C1, 5 in C2, and 2 in C3) were achieved as the best response. IFN had no relevant impact on PK of SOR. Conclusions: SOR/IFN combination has promise for clinical benefit in RCC, and its recommended dose was continuous SOR 400 mg bid and IFN 6 MIU tiw. [Table: see text]
Phase I Trial of Sunitinib Malate plus Interferon-α for Patients with Metastatic Renal Cell Carcinoma