A PHASE-II TRIAL OF HUMAN RECOMBINANT INTERLEUKIN-2 ADMINISTERED AS A4-DAY CONTINUOUS-INFUSION FOR CHILDREN WITH REFRACTORY NEUROBLASTOMA,NON-HODGKINS-LYMPHOMA, SARCOMA, RENAL-CELL CARCINOMA, AND MALIGNANT-MELANOMA - A CHILDRENS CANCER GROUP STUDY

Background. Recombinant human Interleukin-2 (IL-2) has been effective at inducing measurable antitumor responses in adults with renal cell c arcinoma and melanoma. It also is being tested as adjuvant therapy for patients with acute myeloid leukemia after autologous bone marrow tra nsplantation. Methods. The authors tested IL-2 in a pediatric Phase II trial using a regimen that has antitumor effects in adults and was pr oven to be tolerated acceptably in a prior Phase I pediatric trial. Th irty-eight patients were entered into this study of whom 36 received I L-2 and were evaluable (20 with sarcoma, 9 with neuroblastoma, 5 with renal cell carcinoma, and I each with melanoma and lymphoma). Results. Interleukin-2 dose modifications were based on tolerance and toxicity , such that 46% of these patients received a 50% increase in IL-2 dose during the second week, and 81% of those receiving the elevated dose continued receiving this dose level during the third week of treatment . A single patient with renal cell carcinoma had a complete response t hat was maintained; the remaining 35 patients did not show objective e vidence of tumor response sufficient to qualify as either a complete r esponse or a partial response. Conclusions. Absolute lymphocyte counts were indicative of the immunostimulatory effect of this IL-2 regimen as observed for adults, with a median 7.2-fold increase. Nevertheless, despite immune activation, a sufficient number of patients were evalu ated, indicating that IL-2 does not have measurable antitumor effects in children with large refractory sarcomas or neuroblastomas, whereas one of five children with renal cell carcinoma had a complete response , consistent with the 10-20% response rate observed in adults.