title: Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma.
abstract: OBJECTIVE
  Thymosin alpha 1 (Talpha1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining Talpha1 with dacarbazine (DTIC) and interferon alfa (IFN-alpha) in patients with metastatic melanoma.
  
  
  METHODS
  Four hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC+IFN-alpha+Talpha1 (1.6 mg); DTIC+IFN-alpha+Talpha1 (3.2 mg); DTIC+IFN-alpha+Talpha1 (6.4 mg); DTIC+Talpha1 (3.2 mg); DTIC+IFN-alpha (control group). The primary end point was best overall response at study end (12 months). Secondary end points included duration of response, overall survival (OS), and progression-free survival (PFS). Patients were observed for up to 24 months.
  
  
  RESULTS
  Ten and 12 tumor responses were observed in the DTIC+IFN-alpha+Talpha1 (3.2 mg) and DTIC+Talpha1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P(0) < or = .05 (expected response rate of standard therapy) in these two arms. Duration of response ranged from 1.9 to 23.2 months in patients given Talpha1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given Talpha1 versus 6.6 months in the control group (hazard ratio = 0.80; 9% CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given Talpha1 versus the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.01; P = .06). Addition of Talpha1 to DTIC and IFN-alpha did not lead to any additional toxicity.
  
  
  CONCLUSIONS
  These results suggest Talpha1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.
authors.affiliation: Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. mmaio@cro.it
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mackiewicz
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Uwe
authors.initials: U
authors.lastname: Trefzer
authors.forename: Virginia
authors.initials: V
authors.lastname: Ferraresi
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.forename: Thierry
authors.initials: T
authors.lastname: Lesimple
authors.forename: Bernard
authors.initials: B
authors.lastname: Guillot
authors.forename: Pere
authors.initials: P
authors.lastname: Gascon
authors.forename: Katalin
authors.initials: K
authors.lastname: Gilde
authors.forename: Roberto
authors.initials: R
authors.lastname: Camerini
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008875:Middle Aged; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D016898:Interferon-alpha; D013947:Thymosin; D003606:Dacarbazine; D000077596:Thymalfasin