Keilholz U, Eggermont A M
Department of Medicine III (Hematology, Oncology and Transfusion Medicine), University Hospital Benjamin Franklin, Free University of Berlin, Germany.
Cancer J Sci Am. 2000 Feb;6 Suppl 1:S99-103.
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.
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.
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.
Mature results defining the role and, to some extent, the mechanism of IL-2 in advanced melanoma are emerging.