Novel Strategies for Granulocyte Colony-Stimulating Factor

A b stract P urp ose: T o imp rov e the ef f ectiv enes s of g ranu locy te colony -s timu lating f actor ( G -C SF ) treatment in hig h-ris k neu trop enic p atients . E x p erimental D esign: W e s tu dy G -C SF ef f ects on chemotherap y -indu ced neu trop enia b y ex p anding a s imp le mathematical model of neu trop hil dy namics in the b lood. T he f inal model is f itted and v alidated u s ing p u b lis hed clinical data of neu trop hil res p ons e to chemotherap y and s tandard s . c. G -C SF p rotocol ( SG ; f ilg ras tim 5 A g / k g / d) , s ing le p eg y lated ( p eg G ; p eg f ilg ras tim 1 0 0 A g / k g ) , and continu ou s inf u s ion ( C G ; f ilg ras tim 1 0 A g / k g / d) . T he interp atient v ariab ility is s tu died b y M onte-C arlo s imu lation of p eg G comp ared w ith SG and p laceb o. R esults: T he ef f ect G -C SF s u p p ort on neu trop enia dep ends on the neu trop hil cou nt at the nadir. T hree dis tinct neu trop enia g rades are identif ied: G 1 ( 30 0 1 0 -5 0 0 1 0 3 cells / mL ) , G 2 ( 5 0 1 0 -30 0 1 0 3 cells / mL ) , and G 3 ( V5 0 1 0 3 cells / mL ) . F or many G 2 p atients , the G -C SF lev els req u ired f or recov ery are not attainab le b y the s tandard reg imen, w hereas the s u s tained p eg G and C G s eem to b e s ig nif icantly more ef f ectiv e. F or G 3 p atients , G -C SF s u p p ort alone is not s u f f icient and additional clinical ap p roaches s hou ld b e cons idered. T he res u lts p res ented here are rob u s t and are only s lig htly af f ected b y p op u lation v ariab ility . Conclusions: T he model cap tu res the G -C SF -neu trop hil dy namics of s ev ere chemotherap y indu ced neu trop enia. O u r res u lts clarif y and comp lement the cu rrent A merican Society of C linical O ncolog y recommendations f or G -C SF adminis tration in neu trop enia: H ig h s u s tained G -C SF lev els are needed to treat s ev ere neu trop enia and may b e achiev ed b y either C G or p eg G . T he p otential ef f ect of s u s tained G -C SF on s ev ere neu trop enia s hou ld b e s tu died w ithin a f ramew ork of a p ros p ectiv e randomized clinical trial.