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

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 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 os compared with that in G- CSF-treoted patients (P = .0009 and P = .0026, respectively), who required o significantly higher number of leukaphereses than G-CSF + EPO-treated patients (P = .0076) to obtain the planned minimum dose of PBPCs. Qualitative analysis 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 G-CSF administration after chemotherapy. This biologic property of EPO translated in viva into a global improvement of patients' hematologic status.