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 reduce myelosuppression and provide an alternative to the use of stem cell 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 sensitivity to chemotherapy or by depleting stem cell pools. We performed a Phase I/II trial of sequential interleukin 3 (IL-3)/granulocyte colony-stimulating factor (G-CSF) prior to and following high-dose etoposide and 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/microliter or stopped rising. Chemotherapy was started 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 chemotherapy. Twenty-five eligible patients with Hodgkin's disease, non-Hodgkin's lymphoma, or breast cancer were enrolled. Priming was generally well tolerated. The median maximum WBC count and absolute neutrophil count achieved was 66,400 and 57,600/microliter, respectively. Significant decreases in platelet counts were seen during priming with 15 patients having a >/=40% decrease from prepriming values. Hematological recovery of study patients was compared to that of an unprimed historical control group (n = 38) treated with the same chemotherapy followed by G-CSF alone. Neutrophil recovery to 500 and 1000/microliter and platelet recovery to >/=50,000/microliter was significantly faster in the study group compared to that of historical controls (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 randomized trials to patients treated with only postchemotherapy IL-3 and G-CSF and to patients treated with peripheral blood stem cell support.
Bernstein
S H
SH
Departments of Hematological Oncology and Bone Marrow Transplantation, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Fay
J P
JP
Christiansen
N P
NP
Pinero
L
L
Shah
D
D
Stephan
M
M
Herzig
G P
GP
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006689:Hodgkin Disease / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D015993:Life Tables; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D010976:Platelet Count / Q000187:drug effects; D011292:Premedication; D012449:Safety; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control; D016896:Treatment Outcome
D007377:Interleukin-3; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D003520:Cyclophosphamide