Appropriate administration of Granulocyte-Colony Stimulating Factors

Abstract

 Chemotherapy-induced febrile neutropenia is a potentially fatal complication of cancer treatment and is also the main reason of dose-reduction and/or delay of chemotherapy regimen. Prophylaxis with G-CSF is applicable to reduce the risk of chemotherapy-induced neutropenia. Two molecules of recombinant G-CSF are available for clinical use: lenograstim, identical to human native G-CSF, that is derived from mammalian cells and filgrastim, different to human native G-CSF, expressed in E coli and commercialized in normal form and pegilated long-acting form. Neutrophil morphology and expected defense functions are modified by treatment with filgrastim, while they are not affected by lenograstim. These functionality differences observed in vitro are recently confirmed in a clinical trial that shows a lower incidence of febrile episodes with lenograstim compared to filgrastim in presence of G-CSF induced neutrophils. The long-term safety of lenograstim was supported by the results of a prospective, longer-term study involving almost 4,000 healthy donors. Another important question is the respect of timing of administration of G-CSF and chemotherapy. Absolutely in no case the plasma concentration of G-CSF is to be detected 48h before to 24h post chemotherapeutic drugs administration. In fact, this combination could result in an increased risk of mielotoxicity and a potential for an increase in sensitivity of rapidly dividing myeloid cells to cytotoxic-mutagenic chemotherapy potential. Lenograstim and filgrastim shows short half-life time, instead pegfilgrastim shows detectable concentrations for 16 days after a single administration. This is important to be considered, in particular in bi-weekly and tri-weekly adjuvant chemotherapy regimens. Anyway, the use of the lowest effective dose for the shortest adequate time of medications ensures the optimal balance among effectiveness, safety and costs of treatments, in a context that takes into account effectiveness and efficiency.