Randomized, double-blind, placebo-controlled, phase III study of recombinant human granulocyte-macrophage colony-stimulating factor as adjunct to induction treatment of high-grade malignant non-Hodgkin's lymphomas.
We evaluated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; Sandoz Pharma [Basel, Switzerland]/Schering-Plough [Kenilworth, NJ]) as an adjunct to a modified (mainly cyclophosphamide and doxorubicin increased 1.5-fold) COP-BLAM regimen in the primary treatment of high-grade malignant non-Hodgkin's lymphomas (NHL). Patients (n = 182; stage II-IV; age, 15 to 73 years) were randomized to rhGM-CSF (400 micrograms) or placebo for 7 days subcutaneously after chemotherapy. Efficacy was analyzed for patients receiving at least 70% of study medication (n = 125). The frequency of clinically relevant infection was reduced by rhGM-CSF (28 v 69 infections, 16 v 30 patients, P = .02) with a cumulative probability of remaining infection free in 70% versus 48% (P = .05 log rank test at 190 days). Periods of neutropenia (P = .01 in 5 of 6 courses), days with fever (2.1 v 4.0, P = .04) and days of hospitalization for infection (3.5 v 8.0 days, P = .01) were significantly reduced. Complete response (CR) rates, assessed by prognostic risk, were 15 of 19 (79%) in treated versus 20 of 21 (95%) in controls in the low-risk group (P = .12). In the high-risk group, 31 of 45 (69%) treated patients achieved CR versus 25 of 52 (48%) of controls (P = .04). No difference in survival has been seen after 1 year. Only injection site reactions (45% treated v 7% controls) and rash (26% v 2%) occurred more frequently in treated patients (n = 176). These data show that rhGM-CSF is well tolerated in most patients with NHL, significantly reduces infection, and improves response.
Gerhartz
H H
HH
Medical Department III, Klinikum GroBhadem, Munich University, Germany.
Engelhard
M
M
Meusers
P
P
Brittinger
G
G
Wilmanns
W
W
Schlimok
G
G
Mueller
P
P
Huhn
D
D
Musch
R
R
Siegert
W
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000517:prevention & control; D001761:Bleomycin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010976:Platelet Count / Q000187:drug effects; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D000906:Antibodies; D011994:Recombinant Proteins; D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D011241:Prednisone