The role of interleukin-2 in the management of stage IV melanoma: the EORTC melanoma cooperative group program.
OBJECTIVE
To review the current information available from the European Organization for Research and Treatment of Cancer (EORTC) programs on the use of interleukin (IL)-2 in stage IV melanoma patients.


METHODS
A database from 631 patients treated within 27 trials with high-dose IL-2-based regimens was compiled to develop hypotheses and valid stratification factors for randomized trials. Subsequently, 126 patients were enrolled in a trial evaluating interferon alfa (IFN-alpha) and IL-2 with or without cisplatin, and 325 patients were enrolled in an ongoing EORTC trial (18951) to evaluate dacarbazine, cisplatin, and IFN-alpha, with or without IL-2.


RESULTS
The database suggests long-term survival rates of 23% and a 5-year survival rate of 13% for patients receiving a combination of IFN-alpha and IL-2 with or without chemotherapy. The addition of chemotherapy improved response rate but not survival. The first randomized trial testing the role of cisplatin in a chemoimmunotherapy regimen for advanced melanoma revealed a palliative effect for cisplatin but no survival benefit. The current trial (EORTC 18951), which is testing the impact of IL-2 on survival, is still immature. In the translational research program, we have evidence that patients in continuous complete remission after IL-2-based treatment have evidence of residual disease by polymerase chain reaction assay and, at the same time, melanoma-reactive T cells are present in the peripheral blood.


CONCLUSIONS
Mature results defining the role and, to some extent, the mechanism of IL-2 in advanced melanoma are emerging.
Keilholz
U
U
Department of Medicine III (Hematology, Oncology and Transfusion Medicine), University Hospital Benjamin Franklin, Free University of Berlin, Germany.
Eggermont
A M
AM
D002945:Cisplatin / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003606:Dacarbazine / Q000627:therapeutic use; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use*; D008545:Melanoma / Q000401:mortality / Q000628:therapy*; D009367:Neoplasm Staging; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology
D016898:Interferon-alpha; D007376:Interleukin-2; D003606:Dacarbazine; D002945:Cisplatin