Prophylactic Filgrastim (G-CSF) During Mitomycin-C, Mitoxantrone, and Methotrexate (MMM) Treatment for Metastatic Breast Cancer

Abstract

Patients with metastatic breast cancer were randomly assigned to receive as second-line chemotherapy either MMM (mitomycin 8 mg/m2 day 1; mitoxantrone 8 mg/m2 days 1 and 22; methotrexate 35 mg/m2 days 1 and 22) alone or in combination with filgrastim (5 micrograms/kg s.c. days 4-17, 24-37). The courses were repeated every 42 days for a maximum of six courses. Thirty-one patients are evaluable for safety and efficacy. The 16 patients in the filgrastim arm received a total of 42 cycles compared with 34 cycles in the 15 control patients. Tumor responses were few in both patient groups (one partial response in the filgrastim group and two partial responses in control group). Nevertheless, a difference in survival was seen (filgrastim median 10.7 months, control median 6.5 months; p = 0.02 log rank). The treatment was well tolerated. Doses were reduced six times in the filgrastim arm and eleven times in the control arm. Grade IV neutropenia was seen in four patients in the filgrastim arm and in twelve patients in the control arm. The observed survival benefit needs to be confirmed in a larger patient group.

Effectiveness of daily versus non‐daily granulocyte colony‐stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice

“…The study cohort included a highly heterogeneous group of patients, with many tumour types at different stages who received distinct chemotherapy regimens. The efficacy of G-CSFs in solid tumours has been proven mainly in randomised trials including patients with breast cancer, sarcoma or small cell lung cancer (Crawford et al 1991;Bui et al 1995;Muhonen et al 1996;Gatzemeier et al 2000;Timmer-Bonte et al 2005;Vogel et al 2005), but data from other tumour types are scarce. Observational studies suggest that the effectiveness of G-CSFs is independent of tumour location and, in fact, current NCCN guidelines for use of myeloid growth factors are common to all malignancies (NCCN 2012).…”

“…Daily G-CSFs, such as filgrastim or lenograstim, should be administered daily until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range, which usually requires up to 2 weeks of treatment. In clinical trials where daily G-CSFs were continued until either the neutrophil count reached Ն10 ¥ 10 9 /L or for up to 14 days, whichever occurred first, the mean duration of G-CSF prophylaxis was up to 10-11 days (Dale et al 1993;Muhonen et al 1996;Bishop et al 2000;Holmes et al 2002b;Green et al 2003;Siena et al 2003). However, several observational studies have reported that in most patients treated in the clinical practice, duration of prophylaxis with daily G-CSFs is less than 7 days, and that a short duration of daily G-CSF treatment is associated with worse neutropenia-related clinical outcomes (Weycker et al 2006;Morrison et al 2007).…”

A Systematic Overview of Chemotherapy Effects in Breast Cancer

“…The potential positive effect on survival is only reported from a small Finnish study of 32 patients demonstrating a statistically signi cantly (p¾ 0.02) improved median survival, 10.7 vs 6.5 months using Mito-based second line polychemotherapy (250).…”

Granulocyte colony-stimulating factor with or without stem cell factor extends time to premature ovarian insufficiency in female mice treated with alkylating chemotherapy

“…In vivo, the combination of G-CSF and SCF has been shown to increase the number of bone marrow-derived endothelial cells in different organs after ischemia (29). The G-CSF has an established safety profile and is successfully used in cancer patients for prevention of chemotherapy-induced neutropenia without decreasing the efficacy of chemotherapeutic agents (30, 31). …”