title: Durable responses and reversible toxicity of high-dose interleukin-2 treatment of melanoma and renal cancer in a Community Hospital Biotherapy Program.
abstract: BACKGROUND
  High-dose interleukin-2 (IL-2) has been FDA-approved for over 20 years, but it is offered only at a small number of centers with expertise in its administration. We analyzed the outcomes of patients receiving high-dose IL-2 in relation to the severity of toxicity to ascertain if response or survival were adversely affected.
  
  
  METHODS
  A retrospective analysis of the outcomes of 500 patients with metastatic renal cell carcinoma (RCC) (n = 186) or melanoma (n = 314) treated with high-dose IL-2 between 1997 and 2012 at Providence Cancer Center was performed. IL-2 was administered at a dose of 600,000 international units per kg by IV bolus every 8 hours for up to 14 doses. A second cycle was administered 16 days after the first and patients with tumor regression could receive additional cycles. Survival and anti-tumor response were analyzed by diagnosis, severity of toxicity, number of IL-2 cycles and subsequent therapy.
  
  
  RESULTS
  The objective response rate in melanoma was 28% (complete 12% and partial 16%), and in RCC was 24% (complete 7% and partial 17%). The 1-, 2- and 3-year survivals were 59%, 41% and 31%, for melanoma and 75%, 56% and 44%, for RCC, respectively. The proportion of patients with complete or partial response in both melanoma and RCC was higher in patients who a) required higher phenylephrine doses to treat hypotension (p < 0.003), b) developed acidosis (bicarbonate < 19 mmol (p < 0.01)), or c) thrombocytopenia (<50, 50-100, >100,000 platelets; p < 0.025). The proportion achieving a complete or partial response was greater in patients with melanoma who received 5 or more compared with 4 or fewer IL-2 cycles (p < 0.0001). The incidence of death from IL-2 was less than 1% and was not higher in patients who required phenylephrine.
  
  
  CONCLUSIONS
  High-dose IL-2 can be administered safely; severe toxicity including hypotension is reversible and can be managed in a community hospital. The tumor response and survival reported here are superior to the published literature and support treating patients to their individualized maximum tolerated dose. IL-2 should remain part of the treatment paradigm in selected patients with melanoma and RCC.
authors.affiliation: Providence Cancer Center, Providence Portland Medical Center, Earle A. Chiles Research Institute, 4805 NE Glisan Street, Portland, OR 97213, USA.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Payne
authors.affiliation: Providence Cancer Center, Providence Portland Medical Center, Earle A. Chiles Research Institute, 4805 NE Glisan Street, Portland, OR 97213, USA.
authors.forename: Lyn
authors.initials: L
authors.lastname: Glenn
authors.affiliation: Providence Cancer Center, Providence Portland Medical Center, Earle A. Chiles Research Institute, 4805 NE Glisan Street, Portland, OR 97213, USA.
authors.forename: Helena
authors.initials: H
authors.lastname: Hoen
authors.affiliation: Providence Cancer Center, Providence Portland Medical Center, Earle A. Chiles Research Institute, 4805 NE Glisan Street, Portland, OR 97213, USA.
authors.forename: Beverley
authors.initials: B
authors.lastname: Richards
authors.affiliation: Compass Oncology, 265 N Broadway, Portland, OR 97725, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Smith
authors.affiliation: Compass Oncology, 265 N Broadway, Portland, OR 97725, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Lufkin
authors.affiliation: Providence Cancer Center, Providence Portland Medical Center, Earle A. Chiles Research Institute, 4805 NE Glisan Street, Portland, OR 97213, USA.
authors.forename: Todd S
authors.initials: TS
authors.lastname: Crocenzi
authors.affiliation: Providence Cancer Center, Providence Portland Medical Center, Earle A. Chiles Research Institute, 4805 NE Glisan Street, Portland, OR 97213, USA.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.affiliation: Providence Cancer Center, Providence Portland Medical Center, Earle A. Chiles Research Institute, 4805 NE Glisan Street, Portland, OR 97213, USA.
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Curti
keywords: Interleukin-2; Melanoma; Renal cancer