Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) given as daily short infusions--a phase I dose-toxicity study.

2.50
Hdl Handle:
http://hdl.handle.net/10541/107807
Title:
Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) given as daily short infusions--a phase I dose-toxicity study.
Authors:
Steward, William P; Scarffe, J Howard; Austin, R; Bonnem, E; Thatcher, Nick; Morgenstern, Godfrey R; Crowther, Derek
Abstract:
Twenty patients with progressive metastatic solid tumours were entered into a study to evaluate the biological effects and toxicity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF was given as half-hour intravenous infusions during two 10-day phases of daily treatments (separated by 10 days without GM-CSF) and over a final phase of 20 days of alternate day infusions. Doses were escalated in steps from 0.3 to 60 micrograms kg-1 day-1 between successive patient groups. Significant increases (P less than 0.005) of total leucocyte, neutrophil and eosinophil polymorph counts were seen over the periods of daily infusions (up to four-fold rises of total white count) at dose levels of 10 micrograms kg-1 and above. Counts produced at 30 micrograms kg-1 were significantly higher than at 10 micrograms kg-1 (P less than 0.025). Toxic side effects of GM-CSF included mild transient pyrexias, bone pain and pruritus. The maximum tolerated dose was 60 micrograms kg-1, which produced severe toxicity in 80% of patients. The toxicity at this dose included pericarditis and dyspnoea ascribed to a 'capillary-leak' syndrome. One patient receiving 60 micrograms kg-1 died as a result of a pulmonary embolus. Seven patients with previously rapidly progressive metastatic tumours experienced stabilisation of disease while receiving GM-CSF and one patient with a previously heavily pretreated metastatic soft tissue sarcoma underwent a greater than 50% reduction of tumour volume. Patients undergoing chemotherapy may benefit both from a reduction of the myelosuppressive effects of cytotoxic agents and from an antitumour effect if GM-CSF is incorporated into future regimens.
Affiliation:
CRC Department of Medical Oncology, Christie Hospital, Manchester, UK.
Citation:
Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) given as daily short infusions--a phase I dose-toxicity study. 1989, 59 (1):142-5 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Jan-1989
URI:
http://hdl.handle.net/10541/107807
PubMed ID:
2667607
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorSteward, William Pen
dc.contributor.authorScarffe, J Howarden
dc.contributor.authorAustin, Ren
dc.contributor.authorBonnem, Een
dc.contributor.authorThatcher, Nicken
dc.contributor.authorMorgenstern, Godfrey Ren
dc.contributor.authorCrowther, Dereken
dc.date.accessioned2010-07-16T15:11:33Z-
dc.date.available2010-07-16T15:11:33Z-
dc.date.issued1989-01-
dc.identifier.citationRecombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) given as daily short infusions--a phase I dose-toxicity study. 1989, 59 (1):142-5 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid2667607-
dc.identifier.urihttp://hdl.handle.net/10541/107807-
dc.description.abstractTwenty patients with progressive metastatic solid tumours were entered into a study to evaluate the biological effects and toxicity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF was given as half-hour intravenous infusions during two 10-day phases of daily treatments (separated by 10 days without GM-CSF) and over a final phase of 20 days of alternate day infusions. Doses were escalated in steps from 0.3 to 60 micrograms kg-1 day-1 between successive patient groups. Significant increases (P less than 0.005) of total leucocyte, neutrophil and eosinophil polymorph counts were seen over the periods of daily infusions (up to four-fold rises of total white count) at dose levels of 10 micrograms kg-1 and above. Counts produced at 30 micrograms kg-1 were significantly higher than at 10 micrograms kg-1 (P less than 0.025). Toxic side effects of GM-CSF included mild transient pyrexias, bone pain and pruritus. The maximum tolerated dose was 60 micrograms kg-1, which produced severe toxicity in 80% of patients. The toxicity at this dose included pericarditis and dyspnoea ascribed to a 'capillary-leak' syndrome. One patient receiving 60 micrograms kg-1 died as a result of a pulmonary embolus. Seven patients with previously rapidly progressive metastatic tumours experienced stabilisation of disease while receiving GM-CSF and one patient with a previously heavily pretreated metastatic soft tissue sarcoma underwent a greater than 50% reduction of tumour volume. Patients undergoing chemotherapy may benefit both from a reduction of the myelosuppressive effects of cytotoxic agents and from an antitumour effect if GM-CSF is incorporated into future regimens.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshColony-Stimulating Factors-
dc.subject.meshDrug Evaluation-
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor-
dc.subject.meshGrowth Substances-
dc.subject.meshHumans-
dc.subject.meshInfusions, Intravenous-
dc.subject.meshLeukocyte Count-
dc.subject.meshNeoplasms-
dc.subject.meshRecombinant Proteins-
dc.titleRecombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) given as daily short infusions--a phase I dose-toxicity study.en
dc.contributor.departmentCRC Department of Medical Oncology, Christie Hospital, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren

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