Retrospective analysis of the safety and efficacy of interleukin-2 after prior VEGF-targeted therapy in patients with advanced renal cell carcinoma.

Cho DC, Puzanov I, Regan MM, Schwarzberg T, Seery V, Lee MY, Liu V, Bhatt R, Koon H, Mier JW, Sosman JA, Atkins MB, McDermott DF
J Immunother. 2009 32 (2): 181-5

PMID: 19238017 · DOI:10.1097/CJI.0b013e3181952b1d

Agents targeting vascular endothelial growth factor (VEGF) signaling have been advocated as frontline therapy for advanced renal cancer. The role of interleukin 2 (IL-2) therapy after resistance to VEGF-targeted therapy remains unexplored. We conducted a retrospective analysis of the tolerability and efficacy of IL-2 therapy in patients who had previously received VEGF-targeted therapy. Twenty-three consecutive patients who received salvage IL-2 therapy were analyzed. Fifteen patients had received prior tyrosine kinase inhibitors (TKIs) (sorafenib or sunitinib), whereas 8 patients had received bevacizumab alone. Six of 23 patients did not receive week 2 of cycle 1 of treatment. All 6 of these patients had received prior TKIs. The incidence of severe cardiac toxicities, including 1 sudden cardiac death, in patients receiving prior TKI was 40% (95% confidence interval, 16.3-67.7%), significantly higher than what is expected from historical experience. Only 1 of 23 patients proceeded to receive a second cycle of IL-2. No patients achieved a partial or complete response to therapy. This retrospective analysis highlights unexpected and severe cardiac toxicities in patients receiving IL-2 after VEGF-targeted TKI therapy. The assumption that IL-2 therapy can be safely administered after TKI therapy may not be valid. Further examination of the safety of this sequential approach is necessary and more cautious patient selection seems warranted.

MeSH Terms (24)

Angiogenesis Inhibitors Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Antineoplastic Agents Benzenesulfonates Bevacizumab Carcinoma, Renal Cell Female Heart Diseases Humans Indoles Interleukin-2 Kidney Neoplasms Male Middle Aged Niacinamide Phenylurea Compounds Pyridines Pyrroles Retrospective Studies Salvage Therapy Sorafenib Sunitinib Vascular Endothelial Growth Factor A

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