Granulocyte-macrophage colony-stimulating factor in association to timed-sequential chemotherapy with mitoxantrone, etoposide, and cytarabine for refractory acute myelogenous leukemia.
Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), given intravenously 5 micrograms/kg per day, was administered on days 4-8 of timed-sequential chemotherapy (TSC) with mitoxantrone, 12 mg/m2 per day on days 1-3, etoposide, 200 mg/m2 per day on days 8-10 and cytarabine, 500 mg/m2 per day on days 1-3 and 8-10, in 22 patients aged < 60 years with refractory acute myelogenous leukemia in an attempt to increase recruitment of leukemic cells in S phase before the second sequence of TSC. Thirty-eight patients treated with TSC without GM-CSF in a previous trial served as historical controls. In GM-CSF-treated patients, median duration of neutropenia < 0.5 x 10(9)/1 was 33 days and of platelet transfusion requirement 30 days, without any increase by comparison with controls. WHO grade 3 or more extra-hematologic toxicity included sepsis in 60% of patients, vomiting in 30%, diarrhea in 15%, hyper-bilirubinemia in 15%, and mucositis in 10%, without any difference with controls. Among 20 evaluable patients six individuals (30%), with a 95% confidence interval (CI) ranging from 12-54% achieved complete remission, 11 (55%, CI 31-77%) did not respond to therapy and three (15%, CI 3-38%) died from infection. There was no demonstrable in vivo proliferation of leukemic cells during the 5 days of administration of GM-CSF. The average percentage of bone marrow cells in S phase in five patients was 4.0 +/- 2.8 on day 4 and 7.0 +/- 7.2 on day 8 (p = NS). In this cohort of patients refractory to cytarabine, addition of GM-CSF did not increase efficacy of TSC by comparison with historical controls.
Archimbaud
E
E
Service d'Hématologie, Hôpital Edouard Herriot, UFR Alexis Carrel, Lyon, France.
Fenaux
P
P
Reiffers
J
J
Cordonnier
C
C
Leblond
V
V
Travade
P
P
Troussard
X
X
Tilly
H
H
Auzanneau
G
G
Marie
J P
JP
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D003561:Cytarabine; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008942:Mitoxantrone