title: gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma.
abstract: BACKGROUND
  Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone.
  
  
  METHODS
  We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival.
  
  
  RESULTS
  The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine-interleukin-2 group, as compared with the interleukin-2-only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%, P=0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P=0.008). The median overall survival was also longer in the vaccine-interleukin-2 group than in the interleukin-2-only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P=0.06).
  
  
  CONCLUSIONS
  In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00019682.).
authors.affiliation: Indiana University Health Goshen Center for Cancer Care, Goshen, IN 46526, USA. dschwart@iuhealth.org
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Schwartzentruber
authors.forename: David H
authors.initials: DH
authors.lastname: Lawson
authors.forename: Jon M
authors.initials: JM
authors.lastname: Richards
authors.forename: Robert M
authors.initials: RM
authors.lastname: Conry
authors.forename: Donald M
authors.initials: DM
authors.lastname: Miller
authors.forename: Jonathan
authors.initials: J
authors.lastname: Treisman
authors.forename: Fawaz
authors.initials: F
authors.lastname: Gailani
authors.forename: Lee
authors.initials: L
authors.lastname: Riley
authors.forename: Kevin
authors.initials: K
authors.lastname: Conlon
authors.forename: Barbara
authors.initials: B
authors.lastname: Pockaj
authors.forename: Kari L
authors.initials: KL
authors.lastname: Kendra
authors.forename: Richard L
authors.initials: RL
authors.lastname: White
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Brendan
authors.initials: B
authors.lastname: Curti
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Leming
authors.forename: Eric D
authors.initials: ED
authors.lastname: Whitman
authors.forename: Jai
authors.initials: J
authors.lastname: Balkissoon
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Reintgen
authors.forename: Howard
authors.initials: H
authors.lastname: Kaufman
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Choyke
authors.forename: Don
authors.initials: D
authors.lastname: Vena
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007376:Interleukin-2; C544395:gp100(209-2M) vaccine