SEQUENTIAL INTERLEUKIN-3 AND GRANULOCYTE-COLONY-STIMULATING FACTOR PRIOR TO AND FOLLOWING HIGH-DOSE ETOPOSIDE AND CYCLOPHOSPHAMIDE - A PHASE I II TRIAL/

Administration of growth factors prior to chemotherapy (priming) may r educe myelosuppression and provide an alternative to the use of stem c ell support for the delivery of dose-intensive therapy. It is possible , however, that such priming may worsen aplasia, either by recruitment of progenitors into cell cycle and thereby increasing their sensitivi ty to chemotherapy or by depleting stem cell pools. We performed a Pha se I/II trial of sequential interleukin 3 (IL-3)/granulocyte colony-st imulating factor (G-CSF) prior to and following high-dose etoposide an d cyclophosphamide to determine the safety and efficacy of priming, IL -3 was given for 7 days, and then G-CSF was given until the WBC count reached a level of 100,000/mu l or stopped rising, Chemotherapy was st arted 48 h after the last dose of G-CSF, Sequential administration of IL-3/G-CSF was repeated beginning 36 h after the last dose of chemothe rapy, Twenty-five eligible patients with Hodgkin's disease, non-Hodgki n's lymphoma, or breast cancer were enrolled, Priming was generally we ll tolerated, The median maximum WBC count and absolute neutrophil cou nt achieved was 66,400 and 57,600/mu l, respectively, Significant decr eases in platelet counts were seen during priming with 15 patients hav ing a greater than or equal to 40% decrease from prepriming values, He matological recovery of study patients was compared to that of an unpr imed historical control group (n = 38) treated,vith the same chemother apy followed by G-CSF alone. Neutrophil recovery to 500 and 1000/mu l and platelet recovery to greater than or equal to 50,000/mu l was sign ificantly faster in the study group compared to that of historical con trols (P = 0.03, 0.05, and 0.01, respectively), Sequential IL-3/G-CSF given prior to and following high-dose etoposide and cyclophosphamide is safe and is a feasible strategy to compare in prospective randomize d trials to patients treated with only postchemotherapy IL-3 and G-CSF and to patients treated with peripheral blood stem cell support.