Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients.
OBJECTIVE
To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients.


METHODS
Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 microg/kg, n = 9; 60 microg/kg, n = 9; 100 microg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 microg/kg/d; part II, 5 microg/kg/d) (control group, n = 8).


RESULTS
Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 microg/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L by day +15. In part II, high levels of circulating CD34(+) cells (> 20 cells/microL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 microg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy.


CONCLUSIONS
A single injection of Ro 25-8315 100 microg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 microg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.
Viens
P
P
Department of Oncology, Institut Paoli-Calmettes, 232 Blvd Sainte Marguerite, 13273 Marseille Cedex 9, France. viensp@marseille.fnclcc.fr
Chabannon
C
C
Pouillard
P
P
Janvier
M
M
Brugger
W
W
Blay
J Y
JY
Oberling
F
F
Capdeville
R
R
Newman
C
C
Méresse
V
V
Xu
Z X
ZX
Platzer
E
E
Van der Auwera
P
P
Maraninchi
D
D
D000328:Adult; D018952:Antigens, CD34 / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003257:Consumer Product Safety; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011994:Recombinant Proteins
D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; C423652:pegylated granulocyte colony-stimulating factor