Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer.
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) greater than or equal to 50 X 10(9) 1(-1) and was initially given at 3 micrograms kg-1 day-1 and escalated to 10 micrograms kg-1 day-1 after 10 days. The infusion was discontinued when the WCC exceeded 50 X 10(9) 1(-1) and after a gap of one week, melphalan was given over 30 min. GM-CSF was recommenced 8 h later and was continued until the neutrophil count had exceeded 0.5 X 10(9) 1(-1) for greater than 1 week. One patient achieved a WCC greater than 50 X 10(9) 1(-1) with GM-CSF 3 micrograms kg-1 day-1, but the other five who entered this phase of the study required dose escalation to 10 micrograms kg-1. No toxicity attributed to GM-CSF was seen. After melphalan, the median times to severe neutropenia (less than 0.5 X 10(9) 1(-1] and thrombocytopenia (greater than 20 X 10(9) 1(-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 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 micrograms 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 as short as have been reported in historical series which have used autologous bone marrow rescue.
Steward
W P
WP
CRC Dept of Medical Oncology, Christie Hospital, Manchester, UK.
Scarffe
J H
JH
Dirix
L Y
LY
Chang
J
J
Radford
J A
JA
Bonnem
E
E
Crowther
D
D
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000493:pharmacokinetics; D004341:Drug Evaluation; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D008558:Melphalan