DOSE INTENSIFICATION OF EPIDOXORUBICIN AND CYCLOPHOSPHAMIDE IN METASTATIC BREAST-CANCER - A RANDOMIZED STUDY WITH 2 SCHEDULES OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

A randomised phase II/III study was conducted in patients with advance d breast cancer to determine the dose intensity achievable through an acceleration of administration of chemotherapy with epidoxorubicin and cyclophosphamide (EC) alone, as compared with the combination of this regimen with two different schedules of granulocyte-macrophage colony stimulating factor (GM-CSF). 73 patients received EC intravenous (i.v .) (epidoxorubicin 100 mg/m(2), cyclophosphamide 600 mg/m(2)) on day 1 (group A), or the same chemotherapy plus sub-cutaneous (s.c.) GM-CSF (5 mu g/kg/day) either from days 3 to 12 (group B) or from days -6 to -3 (group C). The primary objective of the study was the investigation of dose intensity delivered in the three treatment arms, whereas the secondary objective was response rate. A significant increase (P = 0.0 06) in dose intensity of 21% was observed for treatment group B, where as the increase in dose intensity achieved in group C (7%) was not sig nificant (P = 0.086). Response rates (complete response (CR) + partial response (PR)) of 56% were observed in group A, 65% in group B, and 5 7% in group C, respectively. This difference in response rates did not reach statistical significance (P = 0.271). We thus conclude that an acceleration of the EC regimen over the standard schedule could be acc omplished with postchemotherapeutic GM-CSF support, leading to an incr ease in dose intensity, whereas pretherapeutic short-term GM-CSF admin istration did not reach this goal. (C) 1998 Elsevier Science Ltd. All rights reserved.