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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

From the Cattedra di Ematologia, Istituto di Ostetricia e Ginecologia, Università Cattolica del Sacro Cuore, Rome, Italy.

Address reprint requests to Luca Pierelli, MD, Servizio di Ematologia ed Emotrasfusione, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Roma, Italy; email lpierelli{at}nexus.it

PURPOSE AND METHODS: 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.

CONCLUSION: 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.

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