title: Retrospective analysis of the safety and efficacy of interleukin-2 after prior VEGF-targeted therapy in patients with advanced renal cell carcinoma.
abstract: 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.
authors.affiliation: Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. dcho1@bidmc.harvard.edu
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Cho
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Talya
authors.initials: T
authors.lastname: Schwarzberg
authors.forename: Virginia
authors.initials: V
authors.lastname: Seery
authors.forename: Mee-Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Vivian
authors.initials: V
authors.lastname: Liu
authors.forename: Rupal
authors.initials: R
authors.lastname: Bhatt
authors.forename: Henry
authors.initials: H
authors.lastname: Koon
authors.forename: James W
authors.initials: JW
authors.lastname: Mier
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000627:therapeutic use; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D006331:Heart Diseases / Q000209:etiology*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000009:adverse effects*; D000077157:Sorafenib; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D007376:Interleukin-2; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D000077210:Sunitinib