Authors' objectives:

The aim of this overview was to assess the usefulness of sunitinib in patients with clear cell renal carcinoma.

Authors' results and conclusions: One Phase I, two Phase II, and one Phase III clinical trials with relevant information for this report were found. The Phase I study, recommended the use a 50 mg daily dose, p.o for 4 weeks followed by two weeks without treatment. One non-controlled, multicenter Phase II study, published by Motzer et al, included 63 patients with metastatic renal cell carcinoma, who had used cytokines without positive results. Median time to progression was 8.7 months (CI 95%; 5.5-10.7) with a 16.4-month mean survival. Forty per cent (CI 95%; 28%-53%) of the patients experienced partial response and another 27% did not progress during 3 months. Most common adverse effects were fatigue, lymphopenia without infection and asymptomatic lipase increase. Four patients who developed a reduction of cardiac ejection fraction were discontinued. Quality of life assessed using validated questionnaires was similar to that of the general population. Fatigue rates were similar to those of the oncology population who did not present anemia but higher than the general. The other Phase II trial was published by Motzer in 2006. In this study sunitinib was administered to patients with clear cell renal carcinoma who had not responded to prior treatment with cytokines. 105 patients were evaluated. 34% presented partial response (CI 95%, 25%-44%) and a median disease free survival of 8.7 months (CI 95%, 7.8 14.5); the most frequent adverse effects were fatigue (28%) and diarrhea (20%). In the Phase III study, sunitinib is compared with IFN-α as first line systemic treatment in patients with advanced clear cell renal carcinoma (90% of these patients had undergone prior nephrectomy). This study randomized 375 patients to each arm. The median age was 60 and 90% of the patients had prior nephrectomy. The median time to disease progression was 47.3 weeks for sunitinib vs. 24.9 for IFN-α (HR 0.39 - CI95% 0.29-0.52). The objective response rate was 24.8% vs. 4.9% for IFN-α. Eight per cent of the patients with sunitinib had to discontinue treatment due to adverse events, whereas 13 % for IFN-α. Follow-up is still short to assess survival.

Authors' recommendations: There are few clinical trials conducted with sunitinib in patients with advanced renal carcinoma. Two non-controlled and one randomized trial suggest that sunitinib is one of the options as first or second line treatment for cases with Stage IV clear cell renal carcinoma or unresectable recurrences. Sunitinib has not yet demonstrated its benefits in terms of survival or control of related symptoms, but it has proved to improve disease free survival and objective response rates. At present, there are studies that continue assessing the use of this drug in advanced renal cancer patients. Identification of predictive factors of response could help to recognize which subgroups could benefit the most from this medication. More studies and longer follow-ups than reported are required to evaluate the efficacy of the drug as first and/or second line treatment, and to determine if sunitinib in combination with other drugs could provide better results.

Authors' methods: Overview

Project Status: Completed

URL for project: http://www.iecs.org.ar/

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Argentina

Organisation Name: Institute for Clinical Effectiveness and Health Policy

Contact Address: Dr. Emilio Ravignani 2024, Buenos Aires - Argentina, C1414 CABA

Contact Name: info@iecs.org.ar

Contact Email: info@iecs.org.ar

Copyright: Institute for Clinical Effectiveness and Health Policy (IECS)