Short term treatment with Escherichia coli recombinant human granulocyte-macrophage-colony stimulating factor prior to chemotherapy for Hodgkin disease.
BACKGROUND
Granulocyte-macrophage-colony stimulating factor (GM-CSF) administration stimulates the proliferation of hemopoietic progenitors. Shortly (48-96 hours) after its discontinuation, feedback phenomena occur and the progenitor proliferation rate drops below baseline levels. As the quiescence of hyperplastic bone marrow suggests that hemopoietic cells may be refractory to the toxic effects of cytostatic drugs, the decision was made to test the hypothesis that GM-CSF given before chemotherapy may be myeloprotective.


METHODS
Fifty-six patients with newly diagnosed Stage II-IV Hodgkin disease, ages 18-77 years, were randomized to receive GM-CSF (5 microg/kg subcutaneously) or placebo from Day 7 to Day 4 before each chemotherapy administration (6 cycles of a hybrid of mechlorethamine, vincristine, procarbazine, and prednisone with doxorubicin, bleomycin, vinblastine, and dacarbazine). The treatment was considered a success if the delivery rate of chemotherapy was >90% after 3 cycles and >80% after 6 cycles.


RESULTS
Thirty patients received GM-CSF and 26 placebo. The dose intensity (85.2% vs. 79.6%) and the overall success in terms of delivery rate (56.7% vs. 50%) were higher in the GM-CSF group, although these differences were not statistically significant. The neutrophil nadirs were higher in the GM-CSF group during the first three cycles and subsequently similar in both groups.


CONCLUSIONS
No significant differences in terms of myelotoxicity or drug delivery were observed between the two treatment arms. Although the myeloprotective effect of the prechemotherapy administration of GM-CSF seems to be minimal, the data indicate a safe timing between GM-CSF discontinuation and further chemotherapy. Because cumulative myelotoxicity has been observed with other growth factors, given in the interval between the chemotherapy cycles, this may be relevant to the planning of rapid cycling.
Aglietta
M
M
Divisione Universitaria di Oncologia ed Ematologia, Ospedale Mauriziano Umberto I-Istituto per la Ricerca e la Cura del Cancro (I. R.C.C.), Torino, Italy.
Montemurro
F
F
Fagioli
F
F
Volta
C
C
Botto
B
B
Cantonetti
M
M
Racanelli
V
V
Teofili
L
L
Ferrara
R
R
Amadori
S
S
Castoldi
G L
GL
Dammacco
F
F
Levis
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008466:Mechlorethamine / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009503:Neutropenia / Q000517:prevention & control*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011994:Recombinant Proteins; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D011994:Recombinant Proteins; D001761:Bleomycin; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011241:Prednisone