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- Title
Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma.
- Authors
Deplanque, G.; Madhusudan, S.; Jones, P. H.; Wellmann, S.; Christodoulos, K.; Talbot, D. C.; Ganesan, T. S.; Blann, A.; Harris, A. L.
- Abstract
IM862 is a naturally occurring dipeptide (L-glu-L-trp) with immunomodulatory and antiangiogenic properties. A significant anticancer activity has been reported recently in AIDS-related Kaposi's sarcoma, a tumour of endothelial cell origin. The high vascularity and responsiveness to immunotherapy of renal cell carcinoma (RCC) makes such a tumour a potential target for IM862. In all, 25 patients were accrued in a prospective phase II trial using a standard two-step design. The main inclusion criteria were WHO performance status </=2, age over 18 years, expected survival >3 months, normal marrow, kidney and liver functions. IM862 was given intranasally at a dose of 20 mg three times daily. Each cycle consisted of 8 consecutive weeks of treatment. All 25 patients were fully evaluable for response and 24 for toxicities. Median age was 62 years (range 42-76), median WHO PS was 1 (0-2). No grade 2 or 3 toxicities related to the study drug have been recorded. Eight patients had stable disease (SD) and 17 progressed while on treatment. Median survival was 7.9 months (range 2.7-20). Median time to progression was 1.9 months (range 1.2-12.6). Median duration of SD was 6 months (range 5.2-12.6+). Analysis of blood angiogenic markers showed a significant decrease of plasma vascular endothelial growth factor (VEGF) levels after 4 and 8 weeks of therapy. Treatment with IM862 has no toxicity, but does not lead to any significant objective responses in metastatic RCC. IM862 should not be further evaluated as a single agent at these doses and schedule for this population of patients. The decrease in VEGF levels warrants further investigation of IM862 as an antiangiogenic therapy.
- Subjects
VASCULAR endothelial growth factors; RENAL cell carcinoma; RENAL cancer; BONE marrow; BLOOD testing; GROWTH factors; DISEASE progression; RESEARCH; NEOVASCULARIZATION inhibitors; LIVER tumors; CLINICAL trials; OLIGOPEPTIDES; TIME; METASTASIS; LUNG tumors; EVALUATION research; BONE tumors; COMPARATIVE studies; PATHOLOGIC neovascularization; KIDNEY tumors; LONGITUDINAL method
- Publication
British Journal of Cancer, 2004, Vol 91, Issue 9, p1645
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/sj.bjc.6602126