Prospective randomized comparison of morning versus night daily single subcutaneous administration of granulocyte-macrophage-colony stimulating factor in patients with soft tissue or bone sarcoma

BACKGROUND. Hematopoietic growth factors (HGFs) have been used to reduce th e neutropenic complications of cytotoxic chemotherapy so that higher doses may be given. The authors have previously shown that endogenous serum granu locyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) levers at night (p.m.) were significantly highe r than those in the morning (a.m.). METHODS, Twenty-four patients with soft tissue or bone sarcoma who were tre ated with high dose ifosfamide-based chemotherapy were enrolled in this stu dy. Patients were randomized to either a.m. or p.m. treatment. GM-CSF was a dministered at a dose of 5 mu g/kg/day at 10 a.m. or 10 p.m., beginning 36- 48 hours after the last chemotherapy dose. GM-CSF therapy was continued unt il the neutrophil count exceeded 1000/mm(3) for 2 consecutive days. Leukocy te, neutrophil, monocyte, and platelet counts were measured immediately bef ore GM-CSF administration and exactly 12 hours after the first dose of GM-C SF, and every 24 hours until 3 days after the cessation of GM-CSF. RESULTS. The mean duration of Grade 3-4 neutropenia was 5.3 +/- 0.4 days fo r the a.m. treatment arm and 6.5 +/- 0.3 days for the p.m. treatment arm (P = 0.017). Although the duration of neutropenia in the a.m. arm was signifi cantly shorter than in the p.m. arm, there were no differences related to t he number of febrile neutropenic episodes or the duration of antibiotic adm inistration. Also, there were no differences in the side effects observed i n the a.m. and p.m, arms. CONCLUSIONS. The finding of 1.2 days' difference in the duration of Grade 3 -4 neutropenia warrants further study of chronotherapy with HGFs. (C) 2000 American Cancer Society.