Large Randomized Study of Thymosin α 1, Interferon Alfa, or Both in Combination With Dacarbazine in Patients With Metastatic Melanoma

Purpose Thymosin alpha 1 (T alpha 1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining T alpha 1 with dacarbazine (DTIC) and interferon alfa (IFN-alpha) in patients with metastatic melanoma. Patients and Methods Four hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC + IFN-alpha + T alpha 1 (1.6 mg); DTIC + IFN-alpha + T alpha 1 (3.2 mg); DTIC + IFN-alpha + T alpha 1 (6.4 mg); DTIC + T alpha 1 (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 + T alpha 1 (3.2 mg) and DTIC + T alpha 1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P-o <= .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 T alpha 1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given T alpha 1 versus 6.6 months in the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given T alpha 1 versus the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.01; P = .06). Addition of T alpha 1 to DTIC and IFN-alpha did not lead to any additional toxicity. Conclusion These results suggest T alpha 1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.