title: Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte macrophage-colony stimulating factor improves survival for patients responding to induction concurrent biochemotherapy.
abstract: OBJECTIVE
  A prospective Phase II study of a novel maintenance biotherapy regimen after induction biochemotherapy was conducted in patients with metastatic melanoma in efforts to maintain responses and improve survival.
  
  
  METHODS
  Thirty-three patients with poor prognosis metastatic melanoma who achieved a partial response (PR) or stable disease (SD) to induction concurrent biochemotherapy were treated with chronic low-dose interleukin (IL)-2 and granulocyte macrophage-colony stimulating factor, and intermittent pulses of intermediate/high-dose decrescendo IL-2 over a 12-month period. The outcome of these patients was compared with a control group of patients at our institution who were treated recently with induction biochemotherapy and achieved a PR or SD.
  
  
  RESULTS
  Five patients (15%) achieved a complete response, and 4 patients (12%) maintained SD for at least 6 months on maintenance biotherapy. The median progression-free survival (PFS) and overall survival (OS) were 8.1 months and 18.5 months, respectively, compared with historical controls, which were PFS 5.9 months (P = 0.0015) and OS 9.3 months (P = 0.0004). Administration of maintenance biotherapy was a significant predictor of PFS (P = 0.0008) and OS (P = 0.0001) in multivariate and matched-pair analyses (P = 0.002). The maintenance biotherapy regimen was well tolerated with no dose-limiting acute or cumulative toxicities.
  
  
  CONCLUSIONS
  In this single institution study, maintenance biotherapy with IL-2 and granulocyte macrophage colony-stimulating factor in patients achieving PR or SD to induction biochemotherapy improved PFS and OS compared with historical controls. A larger multicenter Phase II trial has been initiated in an effort to confirm these results.
authors.affiliation: John Wayne Cancer Institute, Santa Monica, California 90404, USA. odays@jwci.org
authors.forename: Steven J
authors.initials: SJ
authors.lastname: O'Day
authors.forename: Peter D
authors.initials: PD
authors.lastname: Boasberg
authors.forename: Lawrence
authors.initials: L
authors.lastname: Piro
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kristedja
authors.forename: He-Jing
authors.initials: HJ
authors.lastname: Wang
authors.forename: Maureen
authors.initials: M
authors.lastname: Martin
authors.forename: Regina
authors.initials: R
authors.lastname: Deck
authors.forename: Patricia
authors.initials: P
authors.lastname: Ames
authors.forename: Kelly
authors.initials: K
authors.lastname: Shinn
authors.forename: Hannah
authors.initials: H
authors.lastname: Kim
authors.forename: Patricia
authors.initials: P
authors.lastname: Fournier
authors.forename: Guy
authors.initials: G
authors.lastname: Gammon
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006980:Hyperthyroidism / Q000139:chemically induced; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D015993:Life Tables; D008545:Melanoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D012074:Remission Induction; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D007155:Immunologic Factors; D007376:Interleukin-2; D013629:Tamoxifen; D014747:Vinblastine; D003606:Dacarbazine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin