Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine-arabinoside in the treatment of patients with myelodysplastic syndromes. A phase II study.
As part of a multicenter trial 12 patients with myelodysplastic syndromes (MDS) were treated with 14-day-cycles of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 250 micrograms/m2 day s.c.). In addition, all patients received 20 mg/m2/day s.c. cytosine-arabinoside (Ara-C) 12 h after GM-CSF except for patients suffering from refractory anemia (RA) according to FAB classification. Courses were repeated after 4 weeks. In 11 evaluable patients, results according to FAB-classified MDS were as follows: RA, 1/2 response (R), 1/2 stable disease (SD); RAEB, 2/3 R, 1/3 SD; RAEB-T, 1/6 CR, 1/6 PR, 2/6 R, 2/6 progression; CMML, 1/2 SD. In 2 patients with RAEB-T, overt acute myeloid leukemia was observed 2 and 10 weeks after initiation of treatment. With few exceptions, treatment resulted in a prompt increase in granulocytes and eosinophiles. This was associated with improvement of infectious complications. Increases in red cells and platelets occurred variably and was apparently associated with responses of the underlying disease. Dose limiting side effects consisted of fever, severe fatigue and dolent local reactions at the site of GM-CSF injection. In addition, nausea and diarrhoea occurred frequently. Less often, respiratory and cardiovascular side effects were encountered. In summary, GM-CSF +/- Ara-C in MDS results in objective remission with manageable toxicity. Conceivably, this regimen will serve as a base for future treatment strategies against MDS.
Dept. of Internal Medicine (Cancer Research), West German Tumor Center, University of Essen Medical School.
K
K
Höffken
F
F
Overkamp
J
J
Stirbu
A
A
Grothey
M
M
Flasshove
D
D
Hoelzer
A
A
Ganser
D003115:Colony-Stimulating Factors / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007279:Injections, Subcutaneous; D007958:Leukocyte Count / Q000187:drug effects; D015337:Multicenter Studies as Topic; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor