Granulocyte-macrophage colony-stimulating factor in association with high-dose chemotherapy (VETOPEC) for childhood solid tumors: a report from the Australia and New Zealand Children's Cancer Study Group.
OBJECTIVE
Combination chemotherapy with vincristine, etoposide, and high-dose, escalating cyclophosphamide (VETOPEC) is an effective regimen in pediatric patients with high-risk solid tumors. The toxicity of the regimen is predominantly haematologic. This study addressed the role of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) following each cycle of chemotherapy in decreasing neutropaenia, incidence of fever/ hospitalization, and/or increasing chemotherapy dose-intensity.


METHODS
Twenty-nine children with recurrent solid tumors were treated with the VETOPEC regimen. Sequential cohorts of patients received no GM-CSF (Group I), or GM-CSF in a dosage of 5 micrograms/kg/day (Group II) or 10 micrograms/kg/day (Group III) on days 4-18 of each chemotherapy cycle. Up to four cycles of chemotherapy were analysed with respect to haematopoietic recovery, clinical parameters, and dose intensity.


RESULTS
Neutrophil recovery was significantly more rapid in patients treated with GM-CSF. Time to achieving an absolute neutrophil count (ANC) over 0.5 x 10(9)/L in Groups I, II, and III were 21, 18, and 16 days, respectively (P < 0.0001). Time to achieving an absolute neutrophil count (ANC) over 1.0 x 10(9)/L in Groups I, II, and III were 24, 19, and 17 days, respectively (P < 0.0001). There was no significant difference in the incidence of febrile neutropaenia between the three groups. Febrile neutropaenia occurred following 42, 68, and 62% of chemotherapy cycles in Groups I, II, and III, respectively (P = 0.27). Chemotherapy dose intensity was not different between the three groups. GM-CSF was associated with pericarditis and myalgias in one patient, and transient hypoxia/hypotension in another.


CONCLUSIONS
GM-CSF led to significantly more rapid neutrophil recovery following VETOPEC chemotherapy, but did not lead to any demonstrable clinical benefit, either in reducing febrile events, or in increasing chemotherapy dose intensity.
McCowage
G B
GB
Department of Haematology/Oncology, Sydney Children's Hospital, Randwick, Australia.
White
L
L
Carpenter
P
P
Lockwood
L
L
Toogood
I
I
Tiedemann
K
K
Shaw
P J
PJ
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide