Prognostic factors predictive of response and survival to a modified FOLFOX regimen: importance of an increased neutrophil count.
OBJECTIVE
The aim of this study was to identify prognostic indicators of survival and response in a homogeneous population of chemotherapy-naive patients treated with oxaliplatin as part of 3 successive trials.


METHODS
Patient data were derived from 3 successive phase II trials evaluating modifications of the FOLFOX4 (oxaliplatin/5-fluorouracil/leucovorin) regimen. Clinical and laboratory prognostic factors were identified from the literature. Multifactor analyses stratified by treatment cohort were performed to identify independent prognostic factors for progression-free survival (PFS), overall survival (OS), and response rate.


RESULTS
One hundred thirty-four patients were enrolled across all 3 studies. Reduced PFS (n = 128) was associated with patients with the following characteristics: no previous surgery (P = 0.003); previous adjuvant chemotherapy (P = 0.015); > 1 organ involvement (P = 0.001); baseline absolute neutrophil count (ANC) > or = upper limit of normal (P = 0.001); and time from diagnosis to metastases < 9 months (P = 0.043). Poor OS (n = 128) was associated with patients with the following characteristics: performance status > 1 (P < 0.001); > 1 organ involvement (P = 0.018); and baseline ANC > or = upper limit of normal (P < 0.001). Response rate was related to previous surgery (P = 0.017) and performance status (P = 0.02).


CONCLUSIONS
This analysis has identified the additional prognostic importance of an increased ANC for PFS and OS. Further consideration needs to be given to include markers of systemic inflammation such as ANC as well as relevant cytokine levels in a larger cohort of identically treated patients.
Michael
Michael
M
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Victoria, 8006, Australia. michael.michael@petermac.org
Goldstein
David
D
Clarke
Stephen J
SJ
Milner
Alvin D
AD
Beale
Phillip
P
Friedlander
Michael
M
Mitchell
Paul
P
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D002955:Leucovorin / Q000008:administration & dosage; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009504:Neutrophils; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011379:Prognosis
D009944:Organoplatinum Compounds; D007770:L-Lactate Dehydrogenase; D002955:Leucovorin; D005472:Fluorouracil