Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer

W. P. Steward, J. H. Scarffe, L. Y. Dirix, J. Chang, J. A. Radford, E. Bonnem, D. Crowther

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    Nine patients with progressive, metastatic disease from primary carcinoma of the colon were entered into a phase I/II study using continuous intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and high dose melphalan (120 mg m-2). GM-CSF was given alone to six patients during the first part of the study to determine a dose that would produce a peripheral leucocyte count (WCC) ≥ 50 x 109 l-1 and was initially given at 3 μg kg-1 day-1 and escalated to 10 μg kg-1 day-1 after 10 days. The infusion was discontinued when the WCC exceeded 50 x 109 l-1 and after a gap of one week, melphalan was given over 30 min. GM-CSF was recommended 8 h later and was continued until the neutrophil count had exceeded 0.5 x 109 l-1 for > 1 week. One patient achieved a WCC > 50 x 109 l-1 with GM-CSF 3 μg kg-1 day-1, but the other five who entered this phase of the study required dose escalation to 10 μg kg-1. No toxicity attributed to GM-CSF was seen. After melphalan, the median times to severe neutropenia (<0.5 x 109 l-1) and thrombocytopenia (<20 x 109 l-1) were 6 and 9 days respectively. The median durations of neutropenia and thrombocytopenia were 14 and 10 days respectively. All patients required intensive support with a median duration of inpatient stay of 24 days. There was one treatment related to death due to renal failure. One complete and two partial remissions (33% response rate) were seen but these were of short duration (median of 10 weeks). This study demonstrates that GM-CSF given by continuous intravenous infusion produces significant increments of peripheral granulocyte counts at 3 and 10 μg kg-1 day-1 and is not associated with any toxicity. The duration of neutropenia and thrombocytopenia induced by high-dose melphalan appears to be reduced by the subsequent administration of GM-CSF to times which are at least a short as have been reported in historical series which have used autologous bone marrow rescue.
    Original languageEnglish
    Pages (from-to)749-754
    Number of pages5
    JournalBritish Journal of Cancer
    Issue number5
    Publication statusPublished - 1990


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