Granulocyte-macrophage colony-stimulating factor (GM-CSF) allows acceleration and dose intensity increase of CEF chemotherapy: a randomised study in patients with advanced breast cancer

Abstract

Summary A randomised study was conducted in 62 patients with advanced breast cancer to assess whether granulocyte-macrophage colony-stimulating factor (GM-CSF) would yield an increase in the dose intensity of a standard-dose CEF regimen through an acceleration of chemotherapy administration. Patients received CEF (cyclophosphamide 600 mg m'2, epidoxorubicin 60 mg m-2 and fluorouracil 600 mg m-2) i.v. on day 1 or the same chemotherapy, plus GM-CSF 1Ol g kg-I s.c. starting from day 4, repeated as soon as haematopoietic recovery from nadir occurred. Patients in the CEF + GM-CSF group received chemotherapy at a median interval of 16 days compared with 20 days in the control group. This led to a significant increase (P = 0.02) in the dose intensity actually administered in the third, fourth and sixth cycles: +28%, +25%, +20% respectively. Non-haematological toxicity was mild. GM-CSF had to be reduced or suspended in 50% of patients because of toxicity. Haematological toxicity, mainly cumulative anaemia and thrombocytopenia, was manageable. An increase in response rate for patients with measurable disease, of borderline statistical significance (P= 0.088, P for trend = 0.018), from 42% in the CEF group to 69% in the CEF + GM-CSF group, was observed. This randomised trial indicates that GM-CSF is useful for chemotherapy acceleration. Accelerated CEF + GM-CSF is a moderately dose-intensive regimen that can be administered in an outpatient clinic and is associated with a high objective response.

Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study

“…The maximum SDI reached by a CMF combination in a controlled trial is 1.98. 28 By administering GM-CSF, Ardizzoni et al 29 escalated the SDI of the FEC regimen up to 2.11 units. The projected SDI of our CA-TP and PE-TI regimens for the recommended dose of paclitaxel are 5.42 and 5.16, respectively, higher than that of any multicyclic chemotherapy tested in randomized trial for first-line treatment of metastatic BC.…”

High-dose intensity cyclophosphamide, epidoxorubicin, vincristine and prednisone by shortened intervals and granulocyte colony-stimulating factor in non-Hodgkin's lymphoma: a phase II study

“…In a randomized study carried out in breast cancer patients the intervals between cycles of cyclophosphamide, epidoxorubicin and fluorouracil were reduced and the dose intensity increased by employment of GM-CSF (Ardizzoni et al, 1994). In another study, in breast cancer, dose escalation and interval reduction were randomly compared, resulting in a higher dose intensity with the interval reduction (Lalisang et al, 1997).…”

“…In the present study we investigated the intensification of chemotherapy in combination with G-CSF, by shortening intervals among cycles, in analogy with studies of chemotherapy acceleration carried out in breast (Ardizzoni et al, 1994), ovarian (Pronzato et al, 1996), bladder (Pronzato et al, 1997) and small-cell lung cancer (Ardizzon et al, 1993).…”

Modulations of dose intensity of doxorubicin and cyclophosphamide in association with G-CSF and peripheral blood stem cells in adjuvant chemotherapy for breast cancer: comparative evaluation of completion and safety of three intensive regimens

“…We and others [5][6][7][8][9] were able to develop much larger dose escalation of anthracyclines and cyclophosphamide in breast cancer when hematopoietic growth factors and/or peripheral blood stem cells (PBSC) were added to cycles of chemotherapy. In a previous report, 10 we demonstrated that, when compared to the standard dose intensity of the AC regimen of the NSABBP, we could safely increase the relative dose intensity (RDI) of doxorubicin (ϫ1.25) and cyclophosphamide (ϫ5) (group 1) in intensive outpatient chemotherapy designed for poor risk patients.…”