Background: Although the safety and efficacy of granulocyte-colony-stimulating factor (G-CSF) (filgrastim) in the treatment of hematologic malignancies has been well established, to the authors' knowledge the optimal timing of filgrastim administration during remission induction chemotherapy and consolidation chemotherapy has not been determined. The purpose of the current study was to determine whether a delay in the administration of filgrastim from Day 5 to Day 10 during chemotherapy with a hyper-CVAD (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) regimen resulted in a longer time to neutrophil or platelet count recovery or increased the incidence of infection.
Methods: One hundred ninety-nine patients who achieved complete disease remission after a single course of induction chemotherapy were considered for evaluation. Induction chemotherapy was with hyper-CVAD (fractionated cyclophosphamide, 300 mg/m2, twice daily for Days 1-3; doxorubicin, 50 g/m2, on Day 4; vincristine, 2 mg, on Days 4 and 11; and dexamethasone, 40 mg, on Days 1-4 and Days 11-14), which also was given in odd-numbered consolidation Courses 3, 5, and 7. Even-numbered courses (Courses 2, 4, 6, and 8) were comprised of methotrexate, 200 mg/m2, over 2 hours followed by 800 mg/m2 over 24 hours on Day 1; cytarabine, 3 g/m2, every 12 hours for 4 doses over 2 days (Days 2 and 3); and intravenous methylprednisolone, 50 mg, twice daily on Days 1-3 (MTX/ara-C regimen). Two sequential treatment groups were assessable based on timing of the filgrastim administration; 151 patients received filgrastim starting on Day 5 (D5) of induction chemotherapy and 48 patients received filgrastim starting on Day 10 (D10).
Results: Time to neutrophil recovery was shorter for the D5 group than for the D10 group during induction chemotherapy (18 days vs. 19 days; P = 0.04) and hyper-CVAD Courses 3 and 5 (12 days vs. 15 days during Course 3, P < 0.001; and 13 days vs. 16 days during Course 5, P = 0.002). There was no apparent significant difference between the two groups with regard to time to neutrophil recovery during the MTX/ara-C courses or the last hyper-CVAD course. Delay in the administration of filgrastim did not appear to result in an increase in time to platelet count recovery or in the incidence of infection; however, there was an increased incidence of mucositis during induction chemotherapy.
Conclusions: For a hyper-CVAD and MTX/ara-C regimen, the results of the current study have shown that the administration of filgrastim can be delayed until Day 10 without increasing the risk of treatment-related morbidity during consolidation chemotherapy. During induction chemotherapy, delay in the administration of filgrastim may result in a slight increase in the time to neutrophil count recovery and risk of mucositis, but there is no apparent associated increase in the risk of infection.