title: A randomized, placebo-controlled phase ii study evaluating the reduction of neutropenia and febrile neutropenia in patients with colorectal cancer receiving pegfilgrastim with every-2-week chemotherapy.
abstract: BACKGROUND
  Adding irinotecan and/or oxaliplatin to every-2-week 5-fluorouracil (5-FU)/leucovorin (LV) prolongs survival in patients with colorectal cancer (CRC) but increases neutropenia frequency. Pegfilgrastim is indicated to decrease infection as manifested by febrile neutropenia (FN) in patients receiving chemotherapy at > 14-day intervals. This randomized, placebo-controlled phase II study examined pegfilgrastim efficacy and safety in patients with CRC receiving every-2-week chemotherapy.
  
  
  METHODS
  Patients with CRC were randomized 1:1 to pegfilgrastim 6 mg or placebo administered per-cycle on day 4. Randomization was stratified by chemotherapy regimen (patients received every-2-week FOLFOX4 [5-FU/LV/oxaliplatin], FOLFIRI [5-FU/LV/irinotecan], or FOIL [5-FU/LV/oxaliplatin/irinotecan] at physician discretion). The primary endpoint was incidence of grade 3/4 neutropenia. Secondary endpoints included incidence of grade 3/4 FN and adverse events. After 4 cycles of study treatment, progression-free survival (PFS) and overall survival (OS) were followed for <or= 2 years in long-term follow-up.
  
  
  RESULTS
  Of 241 eligible patients analyzed, 118 were in the placebo and 123 in the pegfilgrastim group. In the treatment period, the odds ratio for grade 3/4 neutropenia for pegfilgrastim versus placebo was 0.19 (95% CI, 0.10-0.37; P < .001); grade 3/4 FN incidence was also significantly lower in pegfilgrastim-treated patients (2%) compared with placebo-treated patients (8%; P = .04). Pegfilgrastim was well tolerated, with leukocyte counts remaining stable during cycles 2-4. In long-term follow-up, both treatment groups had similar PFS and OS.
  
  
  CONCLUSIONS
  Pegfilgrastim was well tolerated in patients with CRC receiving every-2-week chemotherapy and significantly reduced neutropenia and FN compared with placebo, though FN was uncommon in both treatment groups. Results suggest that pegfilgrastim administration is feasible in CRC patients receiving every-2-week chemotherapy.
authors.affiliation: David Geffen School of Medicine at UCLA, Santa Monica, CA 90404, USA. jrhecht@mednet.ucla.edu
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
authors.forename: Madhavan
authors.initials: M
authors.lastname: Pillai
authors.forename: Russell
authors.initials: R
authors.lastname: Gollard
authors.forename: William
authors.initials: W
authors.lastname: Heim
authors.forename: Forrest
authors.initials: F
authors.lastname: Swan
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
authors.forename: Lyndah
authors.initials: L
authors.lastname: Dreiling
authors.forename: May
authors.initials: M
authors.lastname: Mo
authors.forename: Imtiaz
authors.initials: I
authors.lastname: Malik
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002140:California; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016001:Confidence Intervals; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005334:Fever; D000069585:Filgrastim; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy* / Q000453:epidemiology; D016017:Odds Ratio; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012307:Risk Factors; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin