Erythropoietin addition to granulocyte colony-stimulating factor abrogates life-threatening neutropenia and increases peripheral-blood progenitor-cell mobilization after epirubicin, paclitaxel, and cisplatin combination chemotherapy: results of a randomized comparison.
OBJECTIVE
The ability of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) treatment was compared in a randomized fashion with that of G-CSF treatment alone in promoting hematologic recovery and peripheral-blood progenitor-cell (PBPC) mobilization in previously untreated patients with advanced ovarian cancer who underwent their first course of epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy during a phase II study of intensive outpatient ETP chemotherapy followed by high-dose carboplatin, etoposide, and melphalan (CEM) late intensification with PBPC support.


RESULTS
Comparative analysis of hematologic recovery of 50 randomized patients, after ETP chemotherapy, showed that life-threatening neutropenia occurred in 88% of the patients treated with G-CSF alone, whereas it occurred in only 4% of patients treated with G-CSF + EPO. Significantly different WBC and polymorphonuclear leukocyte (PMN) counts were observed in the two distinct arms on the day of WBC nadir (P <.0001 and P <.0001, respectively). Moreover, the addition of EPO to G-CSF increased PBPC mobilization and collection as compared with that in G-CSF-treated patients (P =.0009 and P =.0026, respectively), who required a significantly higher number of leukaphereses than G-CSF + EPO-treated patients (P =.0076) to obtain the planned minimum dose of PBPCs. Qualitative analysis by cloning assay of PBPCs collected in both arms revealed that G-CSF- and G-CSF + EPO-mobilized PBPCs have comparable in vitro functional properties.


CONCLUSIONS
This randomized comparison revealed that EPO significantly increases most of the hematologic effect produced by G-CSF administration after chemotherapy. This biologic property of EPO translated in vivo into a global improvement of patients' hematologic status.
Pierelli
L
L
Cattedra di Ematologia, Istituto di Ostetricia e Ginecologia, Università Cattolica del Sacro Cuore, Rome, Italy. lpierelli@nexus.it
Perillo
A
A
Greggi
S
S
Salerno
G
G
Panici
P B
PB
Menichella
G
G
Fattorossi
A
A
Leone
G
G
Mancuso
S
S
Scambia
G
G
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001772:Blood Cell Count; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004357:Drug Synergism; D015251:Epirubicin / Q000008:administration & dosage; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000097:blood / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D018952:Antigens, CD34; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D017239:Paclitaxel; D002945:Cisplatin