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| |  Sorafenib in Combination With Interleukin-21 Shows Promise for Treatment of Metastatic Renal Cell Carcinoma: Presented at AACR-NCI-EORTC By Crina Frincu-Mallos, PhD SAN FRANCISCO, CA -- October 25, 2007 -- A synergistic effect was observed in the first-in-humans clinical trial of patients with metastatic renal cell cancer treated with the combination of sorafenib and recombinant interleukin-21 (IL-21), researchers reported here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Among the 10 evaluable patients with renal cell carcinoma who have gone on to have two or more rounds of combination treatment, all have experienced tumour shrinkage, and four patients have had at least a 30% reduction in tumour size, said the investigators. "These preliminary data are encouraging, as treatment with sorafenib alone was associated with a confirmed overall response rate of only 2% in the phase 3 trial that led to regulatory approval," said the study's lead investigator, John A. Thompson, MD, Professor of Medicine, Department of Medicine, Division of Oncology, University of Washington, and member of the Fred Hutchinson Cancer Research Center, Seattle, Washington, United States. For all patients accrued in the trial, sorafenib was administered continuously at 400 mg PO BID, while recombinant IL-21 is given intravenously once daily on days 1 to 5 and 15 to 19 of a 6-week treatment course. A total of 13 patients have been enrolled so far in the phase 1 part of the study, which is testing three escalating dose levels (10, 30, or 50 mcg/kg/day) of recombinant IL-21 to estimate the maximum tolerated dose (MTD). "The phase 1 of our study is near completion," said Dr. Thompson. "However, at this point the number of patients treated in our study is still small and it is too early to draw a definite conclusion concerning the efficacy of interleukin-21 in combination with sorafenib compared to use of sorafenib alone," he said. To date, most adverse events seen have been mild and moderate and consistent with the expected toxicities of recombinant IL-21 and sorafenib, Dr. Thompson adds. Among the grade 3 adverse events considered to be possibly or probably related to the study drugs were hypophosphataemia, hyponatraemia, fatigue, and fever. Sorafenib is a tyrosine kinase inhibitor that received approval from U.S. Food and Drug Administration in December 2005. "Although sorafenib does not typically cause a large shrinkage of the tumour, it can prevent the tumour from growing further, and has been shown to delay the progression of kidney cancer," Dr. Thompson said. In addition, Dr. Thompson noted that "immune therapies have been shown to work in kidney cancer in the past, but those previously available were very toxic and poorly tolerated by most patients. Recombinant IL-21 is well tolerated by most patients." For the phase 2 part of the trial, 30 patients will be receiving recombinant IL-21 at the MTD. If these patients have a positive response or at least stable disease after the first 6-week course, they are scheduled to receive the combination therapy. "We expect to proceed to the phase 2 portion of the study by late 2007 or early 2008, to better evaluate the overall safety profile and anti-tumour activity," Dr. Thompson said. Funded for this study was provided by Zymogenetics, which developed recombinant interleukin-21.
[Presentation title: Recombinant IL-21 in Combination With Sorafenib: Preliminary Results from a Phase I/II Study in Patients with Metastatic Renal Cell Cancer. Abstract A60]
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