Phase I Study of Sunitinib in Combination With Gemcitabine and Capecitabine for First-Line Treatment of Metastatic or Unresectable Renal Cell Carcinoma. (20th August 2014)

• Record Type: Journal Article
• Authors: Bellmunt, Joaquim; Suarez, Cristina; Gallardo, Enrique; Rodon, Jordi; Pons, Francesc; Bonfill, Teresa; Beltran, Marta; Moya, Irene; Galtes, Susana; Albanell, Joan; Carles, Joan
• Is Part Of: Oncologist. Volume 19:Number 9(2014)
• Page Start: 917
• Page End: 918
• Publication Date: 2014-08-20
• Subjects: Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2014-0072
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Background: The combination of gemcitabine plus capecitabine and sunitinib (GCS) shows activity in metastatic renal cell carcinoma (mRCC). We tested the multitargeted "chemo-switch" regimen as first-line treatment in patients with mRCC. Methods: We assessed the maximum tolerated dose and antitumor activity of GCS in treatment-naïve, 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 monotherapy at the investigator'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 gemcitabine 1, 000 mg/m 2 per day plus capecitabine 850 mg/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 grade 4 thrombocytopenia). The dose was reduced to DL0 when only 1 of 12 patients experienced DLT (grade 3 diarrhea, grade 3 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 development of the combination is recommended.