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.
CITATION STYLE
Deplanque, G., Madhusudan, S., Jones, P. H., Wellmann, S., Christodoulos, K., Talbot, D. C., … Harris, A. L. (2004). Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma. British Journal of Cancer, 91(9), 1645–1650. https://doi.org/10.1038/sj.bjc.6602126
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