Sunitinib malate (SU) plus interferon (IFN) in first line metastatic renal cell cancer (mRCC): Results of a dose-finding study

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5101 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs and PDGFRs with anti-tumor activity in mRCC patients previously treated with cytokines (JAMA, 2006;295:2516). A phase 3 randomized trial showed superiority for SU over IFN in first-line mRCC (PROC ASCO 24,18S, 2006). Dose and safety for SU combined with IFN was investigated in this phase I trial. Methods: Patients (pts) with previously untreated clear-cell mRCC received SU in repeated 6-week cycles of 50 or 37.5 mg/day orally for 4 weeks, followed by 2 weeks off treatment. IFN was given continuously, starting at 3 MU SC 3x/week with intrapatient dose escalation weekly as tolerated, to a maximum of 9 MU. Pts not tolerating a dose combination received lower doses of SU or IFN, or had dose interruptions. Doses of SU plus IFN were considered tolerable if = 4/6 pts completed 2 cycles without dose reduction or interruption. Results: 25 pts were enrolled; 19 are evaluable for safety/response. 6 pts who started treatment at 37.5 SU and 3 MU IFN are too early. The median age of the 19 pts (16 M: 3 F) was 63 years (range 45–77). MSKCC risk group (JCO 20:289–96, 2002) was 37% good and 63% intermediate. 12 pts started treatment with SU 50 mg and dose escalated IFN to 6 or 9 MU TIW. 13 pts started treatment with SU 37.5 mg and dose escalated IFN at 3 MU or to 6 MU TIW. 4 of 19 pts tolerated two cycles. 68% of pts had dose interruptions of SU; 90% of pts had dose interruptions of IFN. 15/19 pts had grade 3 toxicity, 1 pt had grade 4 hypertension and 1 pt grade 5 toxicity (myocardial infarction). Most common grade 3 toxicities were neutropenia (26%), fatigue (26%), and hand-foot syndrome (16%). Although response was not a primary endpoint, at a median of 3 cycles, there were 2 PR, 14 SD, 2 PD and 1 pt was not evaluable. Conclusions: The adverse events seen with combination SU and IFN in mRCC, neutropenia and fatigue, were similar to those seen with single agent SU and IFN, and resulted in frequent dose modifications and interruptions. The safety and efficacy of 37.5 mg sunitinib and 3 MU IFN is being evaluated. No significant financial relationships to disclose.