Randomized trial of recombinant human interleukin-3 versus placebo in prevention of bone marrow depression during first-line chemotherapy for ovarian carcinoma.
OBJECTIVE
To determine whether recombinant human interleukin-3 (rhIL-3) reduces bone marrow depression and improves chemotherapeutic schedule adherence in ovarian cancer patients receiving first-line combination chemotherapy.


METHODS
In a randomized multicenter study, 185 patients received carboplatin (dose based on projected area under the concentration-time curve [AUC]=4) and cyclophosphamide (750 mg/m2) day 1, every 3 weeks for six cycles. Patients were randomized to receive rhIL-3 (5 microg/kg) or placebo once daily subcutaneously on days 3 to 12.


RESULTS
Adherence to chemotherapeutic regimen, mean chemotherapy cycle length, tumor response rate, and median survival at 24 months did not differ between groups. The number of side effects-primarily allergic reactions, flu-like symptoms and fever-were higher in the rhIL-3 group, which resulted in 21 discontinuations compared with one in the placebo group. Compared with placebo, the rhIL-3 group had higher platelet counts day 1 of cycles 2 to 6. The number of patients with World Health Organization (WHO) grade IV thrombocytopenia or number of platelet transfusions did not differ. Leukocyte counts differed only in cycles 1 and 2 between groups. The leukocyte nadir occurred earlier in the rhIL-3 (day 12) than in the placebo group (day 15, P=.006). Leukocytes and neutrophils were only higher in the rhIL-3 group day 1 of cycle 2. In cycles 4 and 5, more patients with WHO grade IV neutropenia received rhIL-3 (P < .005). Eosinophil counts were higher day 1 of cycles 2 to 6 in the rhIL-3 group (P < .0001).


CONCLUSIONS
rhIL-3 had stimulatory hematopoietic effects. This did not result either in reduction of platelet transfusions or in improvement of chemotherapeutic schedule adherence. There were more side effects in the rhIL-3 group than in the placebo group. rhIL-3 at 5 microg/kg/d is, therefore, not of clinical benefit in this chemotherapeutic regimen.
Division of Medical Oncology, University Hospital Groningen, The Netherlands.
L S
LS
Hofstra
G B
GB
Kristensen
P H
PH
Willemse
A
A
Vindevoghel
H
H
Meden
M
M
Lahousen
F
F
Oberling
B
B
Sorbe
M
M
Crump
I
I
Sklenar
W J
WJ
Sluiter
B
B
Kiese
C G
CG
Trope
E G
EG
de Vries
D000328:Adult; D000368:Aged; D000906:Antibodies; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007377:Interleukin-3 / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use
D000906:Antibodies; D007377:Interleukin-3; D011994:Recombinant Proteins; D003520:Cyclophosphamide; D016190:Carboplatin