Treatment of Febrile Neutropenia

mediastinum due to a noted increased risk of mortality Smith et al. 2006 ; ESMO 2007 . The ASCO guidelines also warn against the use of CSFs when chemotherapy and radiation therapy are being administered jointly Smith et al. 2006 . No pediatric data are available to make recom- mendations for these clinical scenarios. The 2002 pediatric guidelines by Lehrnbecher and Welte recommend against G-CSF usage with concomi- tant chemotherapy and radiation therapy while no mention is made of utilization with radiation therapy alone.

15.2.2 Optimal Administration of Colony-Stimulating Factors

The optimal CSF formulation in pediatric oncol- ogy patients as well as the best dosing schedule, route of administration and timing of administra- tion must all be considered when administering CSFs.

15.2.2.1 Comparison of Granulocyte Colony-Stimulating Factor

and Granulocyte-Macrophage Colony-Stimulating Factor GM-CSF is not FDA approved for treating chemotherapy- induced myelosuppression or febrile neutropenia. A meta-analysis of G-CSF and GM-CSF trials for this purpose in adult oncology patients reported a signifi cantly increased rate of fever in patients receiving GM-CSF, a lack of head to head trials between GM-CSF and G-CSF, and GM-CSF being inef- fective in reducing febrile neutropenia compared with placebo Dubois et al. 2004 . EORTC adult guidelines recommend fi lgrastim, pegfi lgrastim or lenograstim not FDA approved with equipo- tency; ESMO recommends either fi lgrastim or pegfi lgrastim; and ASCO gives consideration for fi lgrastim, pegfi lgrastim and GM-CSF while cau- tioning that there is no long-term data with peg- fi lgrastim and no signifi cant comparative studies between G-CSF and GM-CSF Smith et al. 2006 ; ESMO 2007 ; Aapro et al. 2011 . Pediatric data are lacking. Lydaki et al. 1995 randomized a small cohort of pediatric oncology patients to G-CSF or GM-CSF and found a signifi cant delay in neutrophil recovery in those treated with GM-CSF although this had no bearing on antibi- otic usage or mean hospital stay.

15.2.2.2 Optimal Dosing Adult guidelines recommend dosing of 5 mcgkg

of fi lgrastim, 100 mcgkg of pegfi lgrastim max 6 mg and 250 mcgm 2 of sargramostim Smith et al. 2006 ; ESMO 2007 ; Aapro et al. 2011 . Few pediatric studies are available. Cairo et al. 2001 compared 5 and 10 mcgkg of G-CSF starting 24 h after intensive chemotherapy for 123 pediatric patients with relapsed or refractory solid tumors and found no signifi cant difference in time to ANC ≥1.0 × 10 9 L, incidence of infection, febrile days, incidence of hospitalization or overall sur- vival. A small pediatric study comparing 100 mcgm 2 vs. 250 mcgm 2 of GM-CSF showed that duration of neutropenia was signifi cantly shortened in the 250 mcgm 2 arm with a trend toward decreased duration of febrile neutropenia and no noted difference in side effects Kubota et al. 1995 .

15.2.2.3 Route of Administration

Although package inserts for CSFs consider intravenous and subcutaneous administration to be equipotent, adult data have found that 2–4 times dosing is required to achieve equivalent effect when either G-CSF or GM-CSF is given intravenous as compared to subcutaneous Eguchi et al. 1990 ; Kaneko et al. 1991 ; Stute et al. 1995 ; Honkoop et al. 1996 . Adult guide- lines all suggest subcutaneous administration for CSFs Smith et al. 2006 ; ESMO 2007 ; Aapro et al. 2011 . No pediatric data are available and no mention of route of administration is made in pediatric guidelines Schaison et al. 1998 ; Lehrnbecher and Welte 2002 . In the pediatric clinical setting, intravenous G-CSF is often used when the patient is admitted while subcutaneous dosing is given when at home with no dose adjustment.

15.2.2.4 Optimal Timing

Pediatric guidelines suggest initiation of CSFs 1–5 days after completion of chemotherapy while