Pharmacodynamic effects of haematopoietic cytokines: the view of a clinical oncologist.
The production of haematopoietic cells is under the tight control of a group of haematopoietic cytokines. Each cytokine has multiple actions mediated by receptors whose cytoplasmic domains contain specialized regions initiating survival, proliferation, differentiation commitment, maturation and functional activation. Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoiesis-stimulating agents are in routine clinical use to stimulate cell production and in total have been used in the management of many millions of patients. G-CSF regulates neutrophil production to maintain blood neutrophil counts in the normal range. G-CSF is used to prevent febrile neutropenia or to increase dose-density in chemotherapy regimens. Despite consistently showing a shorter duration of neutropenia, multiple prospective randomized trials have documented only modest clinical benefit. A clinical advantage of dose-dense chemotherapy has been shown only in specific chemotherapy regimens. Professional recommendations tailor the use of CSFs to patients with a high risk of adverse outcome of febrile neutropenia. EPO was used to prevent anaemia requiring red blood cell transfusion. However, recent studies strongly suggest a negative overall effect on mortality, without a plausible biological explanation. It is now proposed that its use should be restricted to patients in clinical trials. Thrombopoiesis-stimulating agents have only been recently introduced into the market for splenectomized and non-splenectomized patients with immune thrombocytopenic purpura, a rare disease. Before widely used in other conditions such as chemotherapy-induced thrombocytopenia, the lessons learned from the example of G-CSF and EPO should be taken seriously.
Held
Thomas K
TK
Department of Haematology, Oncology and Tumour Immunology, Robert-Rössle-Klinik, HELIOS Klinikum Berlin-Buch, Berlin, Germany. thomas.held@helios-kliniken.de
Gundert-Remy
Ursula
U
D002986:Clinical Trials as Topic; D004921:Erythropoietin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D008495:Medical Oncology; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D011994:Recombinant Proteins; D013926:Thrombopoietin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin