title: Southwest Oncology Group S0008: a phase III trial of high-dose interferon Alfa-2b versus cisplatin, vinblastine, and dacarbazine, plus interleukin-2 and interferon in patients with high-risk melanoma--an intergroup study of cancer and leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group.
abstract: OBJECTIVE
  High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration-approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective.
  
  
  METHODS
  S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS).
  
  
  RESULTS
  In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97; P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31; P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms.
  
  
  CONCLUSIONS
  Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI.
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL. flaherty@karmanos.org.
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Flaherty
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Megan
authors.initials: M
authors.lastname: Othus
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Tuthill
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: John T
authors.initials: JT
authors.lastname: Vetto
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Haluska
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Pappo
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Redman
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
authors.affiliation: Lawrence E. Flaherty, Wayne State University, Detroit; Bruce G. Redman, University of Michigan, Ann Arbor, MI; Megan Othus, James Moon, Southwest Oncology Group Statistical Center; John A. Thompson, Seattle Cancer Care Alliance, Seattle, WA; Michael B. Atkins, Georgetown University Hospital, Washington DC; Ralph J. Tuthill, Cleveland Clinic Foundation, Cleveland, OH; John T. Vetto, Oregon Health & Science University/Knight Cancer Institute, Portland, OR; Frank G. Haluska, Tufts-New England Medical Center, Boston, MA; Alberto S. Pappo, Texas Children's Cancer Center, Houston, TX; Jeffrey A. Sosman, Vanderbilt University School of Medicine Nashville, TN; Antoni Ribas, University of California Los Angeles, Los Angeles, CA; John M. Kirkwood, University of Pittsburgh Medical Center, Pittsburgh, PA; Vernon K. Sondak, H. Lee Moffitt Cancer Center, Tampa, FL.
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D014747:Vinblastine; D003606:Dacarbazine; D007372:Interferons; D002945:Cisplatin