The recent FDA approvals of the tyrosine kinase inhibitors sorafenib and sunitinib based on their activity in metastatic renal cell carcinoma have excited the medical oncology community, but one must not forget that these agents are not the panacea for kidney cancer.
Along those lines, clinical investigations are ongoing, evaluating novel agents and combinations of agents in the hopes of improving patient outcome. Two recent publications on phase I/II trials describe the activity of the anti-angiogenic, immunomodulatory agent thalidomide, in combination with subcutaneous interleukin 2 (SCIL-2).
Olencki and colleagues report on their phase I trial with SCIL-2 and thalidomide in 33 patients with metastatic renal cell carcinoma. The MTD of the study was 9.0 mIU/m 2/day SCIL-2 (given for 6 weeks with a 2 week rest period) with 100mg thalidomide. In the study, 30 patients had clear cell histology and 3 had papillary. Ninety-four percent of patients had had prior nephrectomy and 45% of patients had not received prior therapy. Overall toxicity of the regimen was reported as moderate to severe, but most toxicity resolved with dose reduction or discontinuation, and there were no therapy related deaths. The most significant toxicity was neutropenia. There was 1 CR and 1 PR, both in patients with clear cell histology, for an overall response rate of 6%. One minor response was converted to a CR with surgical resection of residual disease that has remained durable. The overall time to progression was 3.7 months and the median survival was not reached. The 1 year survival for the group was 65%.
Amato and colleagues published on their experience with SCIL-2 and thalidomide in a Phase I/II setting. A total of 52 patients were treated with SCIL-2 at a dose of 7 mIU/m 2/day with thalidomide given in doses ranging from 200-600mg. Eight patients in the study had received prior therapy. Fifty-one patients were evaluable. Twenty-seven patients (52%) were reported to have “disease control”. The authors reported 4 CR (8%), 15 PR (29%), and 8 patients with stable disease on therapy (15%). Twenty four patients (47%) demonstrated progressive disease on therapy.
These two studies suggest that there is activity of SCIL-2 and thalidomide in metastatic renal cell carcinoma. The differences in response rates noted between the two studies may reflect the different doses of thalidomide used, or perhaps patient selection, as more than half of the patients in the Olencki study had received prior regimens. Further testing in the phase III setting against other effective therapies will further define the role of this regimen in the treatment paradigm of the practicing oncologist.
By Christopher G. Wood, MD
Invest New Drugs (Epub January 28, 2006)
Olencki T, Malhi S, Mekhail T, Dreicer R, Elson P, Wood L, Bukowski RM.
Cancer (Epub February 10, 2006)
Amato RJ, Morgan M, Rawat A
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