Titre du document / Document title

Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with advanced cancer

Auteur(s) / Author(s)

BASSER R. L. ⁽¹⁾ ; RASKO J. E. J. ⁽⁶⁾ ; CLARKE K. ⁽²⁾ ; CEBON J. ⁽²⁾ ; GREEN M. D. ; HUSSEIN S. ; ALT C. ⁽⁵⁾ ; MENCHACA D. ⁽⁸⁾ ; TOMITA D. ⁽⁸⁾ ; MARTY J. ⁽⁷⁾ ; FOX R. M. ; BEGLEY C. G. ⁽⁴⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Centre for Developmental Cancer Therapeutics, Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Parkville, Victoria, AUSTRALIE
⁽²⁾ Centre for Developmental Cancer Therapeutics, Ludwig Institute Oncology Unit, Austin Repatriation Medical Centre, Parkville, Victoria, AUSTRALIE
Departments of Haematology and Medical Oncology, Centre for Developmental Cancer Therapeutics, Parkville, Victoria, AUSTRALIE
⁽⁴⁾ Centre for Developmental Cancer Therapeutics, Rotary Bone Marrow Research Laboratories, Parkville, Victoria, AUSTRALIE
⁽⁵⁾ Centre for Developmental Cancer Therapeutics, Royal Melbourne Hospital, Western Hospital, Parkville, Victoria, AUSTRALIE
⁽⁶⁾ Centre for Developmental Cancer Therapeutics, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, AUSTRALIE
⁽⁷⁾ Centre for Developmental Cancer Therapeutics, Amgen Australian Kew, Parkville, Victoria, AUSTRALIE
⁽⁸⁾ Amgen, Thousand Oaks, CA, ETATS-UNIS

Résumé / Abstract

Background Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is a potent stimulator of megakaryocyte colony formation and platelet production. It is likely to be useful in the management of severe thrombocytopenia. To determine its clinical activity and safety, we gave it to patients with advanced cancer before chemotherapy. Methods Patients were randomly assigned to receive either PEG-rHuMGDF or placebo in a three to one ratio. PEG-rHuMGDF was given at a dose of 0.03, 0.1, 0.3, or 1.0 μg/kg body weight. The study drug or placebo were administered daily by subcutaneous injection for up to 10 days or until a target platelet count was reached. Findings 17 patients, median age 59 years, received either PEG-rHuMGDF (13 patients) or placebo (four patients). PEG-rHuMGDF produced a dose-dependent increase in platelet counts. Patients given placebo, 0.03, and 0.1 μg/kg of PEG-rHuMGDF had median increases in platelet counts of 16%, 12%, and 39%. Those receiving 0.3 and 1.0 μg/kg of PEG-rHuMGDF had an increase in blood platelets of between 51% and 584%. Platelets rose from day 6 of PEG-rHuMGDF administration and continued to rise after stopping the drug. The platelet count peaked between days 12 and 18 and remained above 450x10⁹/L for up to 21 days. There were no alterations in white-blood-cell count or haematocrit, and low toxicity. Platelets taken from patients during PEG-rHuMGDF administration and at the time of peak platelet count were morphologically and functionally normal. Interpretation The potency with which PEG-rHuMGDF stimulates platelet production and its low toxicity indicate that this is likely to be a useful agent for the management of thrombocytopenia.

Revue / Journal Title

Lancet   ISSN 0140-6736   CODEN LANCAO 

Source / Source

1996, vol. 348, n^o9037, pp. 1279-1281 (23 ref.)

Langue / Language

Anglais

Editeur / Publisher

Lancet, London, ROYAUME-UNI  (1823) (Revue)

Mots-clés anglais / English Keywords

Malignant tumor ; Advanced stage ; Thrombocytopenia ; Chemotherapy ; Toxicity ; Megakaryocyte ; Surgical approach ; Subcutaneous administration ; Histochemistry ; Platelet ; Risk factor ; Human ; Review ; Immunopathology ;

Mots-clés français / French Keywords

Tumeur maligne ; Stade avancé ; Thrombopénie ; Chimiothérapie ; Toxicité ; Mégacaryocyte ; Voie abord ; Voie souscutanée ; Histochimie ; Thrombocyte ; Facteur risque ; Homme ; Article synthèse ; PEG-rHuMGDF ; Immunopathologie ;

Mots-clés espagnols / Spanish Keywords

Tumor maligno ; Estadio avanzado ; Trombopenia ; Quimioterapia ; Toxicidad ; Megacariocito ; Vía abordaje ; Vía subcutánea ; Histoquímica ; Trombocito ; Factor riesgo ; Hombre ; Artículo síntesis ; Inmunopatología ;

Localisation / Location

INIST-CNRS, Cote INIST : 5004, 35400006692975.0110