title: Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma.
abstract: BACKGROUND
  Owing to the limited efficacy of therapy on melanoma at the stage of distant metastases, a well-tolerated adjuvant therapy is needed for patients with high-risk primary melanoma. Our hypothesis was that an adjuvant treatment with low doses of interferon alpha could be effective in patients with localised melanoma.
  
  
  METHODS
  After resection of a primary cutaneous melanoma thicker than 1.5 mm, patients without clinically detectable node metastases were randomly assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for 18 months, or no treatment. The primary endpoint was the relapse-free interval.
  
  
  RESULTS
  499 patients were enrolled, of whom 489 were eligible. When used as part of a sequential procedure, interferon alpha-2a was of significant benefit for relapse-free interval (p=0.038). A long-term analysis, after a median follow-up of 5 years, showed a significant extension of relapse-free interval (p=0.035) and a clear trend towards an increase in overall survival (p=0.059) in interferon alpha-2a-treated patients compared with controls. There were 100 relapses and 59 deaths among the 244 interferon alpha-2a-treated patients compared with 119 relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade 3 or 4 adverse events. Treatment was compatible with normal daily life.
  
  
  CONCLUSIONS
  Adjuvant therapy of high-risk melanoma with low doses of interferon alpha-2a for 18 months is safe and is beneficial when started before clinically detectable node metastases develop.
authors.affiliation: CHR Ste Marguerite, Marseille, France.
authors.forename: J J
authors.initials: JJ
authors.lastname: Grob
authors.forename: B
authors.initials: B
authors.lastname: Dreno
authors.forename: P
authors.initials: P
authors.lastname: de la Salmonière
authors.forename: M
authors.initials: M
authors.lastname: Delaunay
authors.forename: D
authors.initials: D
authors.lastname: Cupissol
authors.forename: B
authors.initials: B
authors.lastname: Guillot
authors.forename: P
authors.initials: P
authors.lastname: Souteyrand
authors.forename: B
authors.initials: B
authors.lastname: Sassolas
authors.forename: J P
authors.initials: JP
authors.lastname: Cesarini
authors.forename: S
authors.initials: S
authors.lastname: Lionnet
authors.forename: C
authors.initials: C
authors.lastname: Lok
authors.forename: C
authors.initials: C
authors.lastname: Chastang
authors.forename: J J
authors.initials: JJ
authors.lastname: Bonerandi
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011994:Recombinant Proteins; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins