Although tyrosine kinase inhibitors (TKI) are the most common first-line therapy for metastatic renal cell carcinoma, high-dose interleukin-2 (HD-IL2) remains the only agent that provides durable complete responses.
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The optimal sequence of these agents remains uncertain. This retrospective multi-institutional study examined the safety and efficacy of HD-IL2 following TKI therapy. After IRB approval at 7 HD-IL2 centers, data relating to patient, disease, and treatment characteristics among 40 consecutive patients with metastatic renal cell carcinoma who were treated with HD-IL2 after at least 1 prior TKI therapy were retrospectively collected. The most common cardiac adverse events were grade 3 hypotension and vascular leak syndrome. Six patients (15%) experienced other grade ≥3 cardiac adverse events. There were 2 treatment-related deaths due to congestive heart failure, occurring in 1 patient with short TKI to HD-IL2 interval and another patient with an abnormal baseline cardiac stress test. Best responses included 2 CRs (5%, duration 40+ and 62+ mo), 3 PRs (8%, duration 6, 11, and 24 mo), 13 SD (32%, median duration 12 mo), 20 PD (50%), and 2 not evaluable patients. Median overall survival was 22 months. Administration of HD-IL2 could be safe and effective after TKI therapy; however, careful selection of patients is critical. We recommend baseline cardiac risk factor assessment, screening with both cardiac stress test and echocardiogram, and allowing a TKI to HD-IL2 interval of at least 2 months.
Lam ET, Wong MK, Agarwal N, Redman BG, Logan T, Gao D, Flaig TW, Lewis K, Poust J, Monk P, Jarkowski A, Sendilnathan A, Bolden M, Kuzel TM, Olencki T. Are you the author?
Departments of Medicine, Division of Medical Oncology, Biostatistics, Pharmacy, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO; Department of Medicine, Division of Medical Oncology, University of Southern California, Los Angeles, CA; Roswell Park Cancer Institute, Department of Pharmacy, Roswell Park Cancer Institute, Buffalo, NY; Department of Medicine, Division of Medical Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, UT; Department of Medicine, Division of Medical Oncology, University of Michigan, Ann Arbor, MI; Department of Medicine, Division of Medical Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Department of Medicine, Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH; Department of Medicine, Division of Medical Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Reference: J Immunother. 2014 Sep;37(7):360-5.