Phase I Study of Sunitinib in Combination With Gemcitabine and Capecitabine for First-Line Treatment of Metastatic or Unresectable Renal Cell Carcinoma

Background.The combination of gemcitabine plus capecita- bineandsunitinib (GCS)showsactivity in metastaticrenal cell carcinoma (mRCC). We tested the multitargeted "chemo- switch"regimenasfirst-linetreatmentinpatientswithmRCC. Methods.We assessed the maximum tolerated dose and antitumor activity of GCS in treatment-na¨ive, advanced mRCC patients. Treatment consisted of intravenous gemcitabine on days 1 and 8, oral capecitabine twice daily on days 1-14, and oral sunitinib daily for six 21-day cycles, followed by sunitinib monotherapyattheinvestigator's discretion. Dose level 0 (DL0) was gemcitabine 1,000 mg/m 2 per day plus capecitabine 650 mg/m 2 per 12 hours plus sunitinib 37.5 mg/day; DL1 was gemcitabine1,000mg/m 2 perdaypluscapecitabine850mg/m 2 per 12 hours plus sunitinib 37.5 mg/day. Results. Sixteen patients were enrolled. At DL1, two of four patients had dose-limiting toxicity (DLT; grade 3 diarrhea and grade4thrombocytopenia).ThedosewasreducedtoDL0when only1of12patientsexperiencedDLT(grade3diarrhea,grade3 mucositis, and grade 3 thrombocytopenia). Dose reductions were frequent (58% of patients), and only seven patients were able to receive the three drugs for more than three cycles. One patient achieved a complete response, three had partial responses, and the best response for four was stable disease. Conclusion.The safety profile of the combination does not seem manageable in this patient population. No further de- velopmentofthecombinationisrecommended.TheOncologist 2014;19:917-918