Growth factors in the profilaxis and treatment of chemotherapy-induced neutropenia

Abstract

Continuous release of granulocyte colony stimulating factor (G-CSF) is indispensable for stable production of neutrophils that are necessary to fight infections. Gene responsible for G-CSF pro­duction was cloned and in 1991 filgrastim (F), was produced with the help of recombinant DNA technology. Febrile neutropenia, a life-threatening complication for patients undergoing chemo­therapy, is the main indication for F or its conjugate with polyethylene glycol, pegfilgrastim (PEGF). Since PEGF, unlike F, is almost exclusively eliminated by neutrophils the exposure to PEGF lasts until full PEGF-induced recovery of neutrophil number is achieved. Both growth factors, namely F (daily) or PEGF (once per cycle) given after chemotherapy reduces: duration (or incidence) of neutropenia, number of infections, days of hospitalization, and mortality. In addition, use of F or PEGF supports dose intensity. The effects of F, PEGF, and lipegfilgrastim (LIPEGF), recently registered pegylated G-CSF, are mediated by specific receptor present in many tissues, including some solid tumors. In these tumors secretion of G-CSF may potentiate tumorigenesis. Apparently, correction of chemotherapy-induced neutropenia using G-CSF carries risks of disease progression in some tumors. Such risk is more probable when cumulative and peak exposure (AUC_inf and C_max) to PEG-CSF is significantly increased, as shown in XM22-04 study of non-small-cell lung carcinoma patients where LIPEGF transiently increased mortality.