Phase I Trial Of Sorafenib In Combination With IFN -2a In Patients With Unresectable And/or Metastatic Renal Cell Carcinoma Or Malignant Melanoma

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials;  Melanoma / Skin Cancer
Article Date: 18 Jun 2007 - 0:00 PDT

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UroToday.com- Therapy for metastatic renal cell carcinoma (RCC) has been revolutionized by the introduction of targeted therapies like sunitinib and sorafenib that target multiple tyrosine kinases, which is important in RCC biology. Sorafenib was developed as a raf kinase inhibitor but is also known to inhibit vascular endothelial growth factor receptor 2 and platelet derived growth factor receptor. As a monotherapy in patients that had failed prior therapies sorafenib demonstrated prolonged time to progression and improved disease response over placebo and subsequently received approval from the FDA for the treatment of RCC. Logically, investigators are now exploring combinatorial therapy with these targeted agents in combination with other drugs that have shown some activity in RCC. Here, Escudier and colleagues report on their phase I experience with sorafenib in combination with interferon -2a (IFN) in patients with advanced RCC and melanoma.

The authors report on 13 patients (12 with RCC, 1 with melanoma) who comprised one of three therapy cohorts. Each cycle of therapy was for 28 days. Cohort 1 received sorafenib 200 mg BID, and thrice weekly injections of 6 MIU IFN. Cohort 2 received sorafenib 400 mg BID and thrice weekly injections of 6 MIU IFN. Cohort 3 received 400 mg BID and thrice weekly injections of 9 MIU IFN. The maximal tolerated dose in the study was not reached and the investigators recommend the dosing in cohort 3 for further study. The major toxicities seen with therapy included fatigue, weight loss, diarrhea, alopecia, and hand-foot syndrome. All but 1 of the patients had failed at least two prior therapies. Therapy was discontinued in 5 patients, two due to toxicity and 3 due to disease progression. There was one partial response (7.7%) and 8 patients had stable disease on therapy (61.5%, including the one melanoma patient). Dynamic contrast enhanced ultrasonagraphy (DCE-US) was used to help characterize tumor response and investigators noted that patients that had a "good" response on DCE-US had an improved progression free and overall survival.

The combination of sorafenib and IFN was well tolerated with minimal increased toxicity with either agent alone. Furthermore, phase II and III studies are needed and ongoing to determine whether this combination provides any incremental benefit over sorafenib alone regarding tumor response and improved patient survival.

Escudier B, Lassau N, Angevin E, Soria JC, Chami L, Lamuraglia M, Zafarana E, Landreau V, Schwartz B, Brendel E, Armand JP, Robert C.

Clin Cancer Res.13(6):1801-09, March 2007.

Reported by UroToday.com Contributing Editor Christopher G. Wood, MD

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