title: Durable complete responses with high-dose bolus interleukin-2 in patients with metastatic melanoma who have experienced progression after biochemotherapy.
abstract: OBJECTIVE
  We conducted a phase II trial of high-dose bolus (HDB) interleukin-2 (IL-2) in patients with metastatic melanoma who had experienced progression after biochemotherapy (BCT).
  
  
  METHODS
  Eligible patients had experienced progression on or after BCT (cisplatin, vinblastine, dacarbazine, IL-2 9 MU/m(2)/d for 4 days, and interferon alfa-2b). HDB IL-2 was administered at 600,000 U/kg per dose for a maximum of 14 doses per cycle with a 1-week rest period between cycles. Stable or responding patients were offered an additional course (two cycles) after 6 to 8 weeks.
  
  
  RESULTS
  Twenty-six patients (12 men and 14 women), age 28 to 70 years (median, 45 years), have been treated. All but three patients received at least two cycles of HDB IL-2; 10 patients received a second course of therapy. Disease stage was American Joint Committee on Cancer (AJCC) stage M1a (n = 5), M1b (n = 5), and M1c (n = 16). Grade 3 and 4 toxicities included hyperbilirubinemia (n = 10), thrombocytopenia (n = 6), oliguria (n = 3), diarrhea (n = 1), infection (n = 2), and neurologic toxicity (n = 2). Overall response rate was 19.2% (four complete responses, lasting 4, 4, 26+, and 41+ months; and one partial response, lasting 3 months). Five patients (19%) had stable disease lasting 1 to 3 months, but all eventually experienced progression. All four complete responders had AJCC stage M1a disease. At a median follow-up time of 10 months, median survival time was 42 weeks (95% CI, 19.1 to 86.6 weeks), and median progression-free survival time was 10 weeks (95% CI, 8 to 16.1 weeks). An initial response to BCT was not found to be predictive for response to HDB IL-2.
  
  
  CONCLUSIONS
  HDB IL-2 is active therapy for patients who experience progression on BCT. This observation has implications regarding the importance of dose-intensity for IL-2 therapy.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Tarhini
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: William E
authors.initials: WE
authors.lastname: Gooding
authors.forename: Chao
authors.initials: C
authors.lastname: Cai
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Agarwala
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin