Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma.
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.
Maio
Michele
M
Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. mmaio@cro.it
Mackiewicz
Andrzej
A
Testori
Alessandro
A
Trefzer
Uwe
U
Ferraresi
Virginia
V
Jassem
Jacek
J
Garbe
Claus
C
Lesimple
Thierry
T
Guillot
Bernard
B
Gascon
Pere
P
Gilde
Katalin
K
Camerini
Roberto
R
Cognetti
Francesco
F
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*
D016898:Interferon-alpha; D013947:Thymosin; D003606:Dacarbazine; D000077596:Thymalfasin