Activity Of Imatinib (Gleevec(R)) In Metastatic Renal Cell Carcinoma

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 07 Mar 2006 - 19:00 PDT


Until recently, standard therapy for metastatic renal cell carcinoma (RCC) has been immunotherapy with either interleukin 2 or interferon. New targeted therapies that target specific molecular pathways important in malignant transformation and progression have been developed and are currently the subject of intense clinical investigation in a variety of malignancies.

Imatinib is one such targeted therapy that has shown clinical activity in CML and GIST tumors. This molecule specifically targets bcr-abl fusion protein, PDGF receptor, the c-kit protooncogene. Previous reports have suggested that c-kit expression was associated with increased stage and grade in RCC and therefore a potentially worthwhile target for therapy. In this report out of Virginia Mason in Seattle, WA by Vuky and colleagues, the activity of this agent in metastatic RCC is examined in a phase II clinical trial.

The authors studied the activity of imatinib in 14 patients with metastatic RCC. Eight patients (57%) had received no prior therapy and 4 patients (29%) had their primary tumor still in place. Eleven patients had clear cell histology, 2 had papillary, and one had chromophobe. Patients were treated with 400 mg BID of imatinib, with 12 patients able to complete one course of therapy (28 days) and were available for analysis. There were no complete or partial responses, although 8 patients (67%) demonstrated stable disease on therapy. All tumors were evaluated with immunohistochemistry for c-kit expression and only the one chromophobe tumor demonstrated significant expression.

Imatinib appears to have little if any activity in RCC based on this small phase II study. The authors note that unlike GIST tumors, no activating mutations of c-kit have been identified in RCC, which may explain its lack of therapeutic benefit.

By Christopher G. Wood, MD

Reference

Invest New Drugs. 2006 Jan;24(1):85-8.

LINK HERE.

Vuky J, Isacson C, Fotoohi M, dela Cruz J, Otero H, Picozzi V, Malpass T, Aboulafia D, Jacobs A.

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