OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer--a GERCOR study.
OBJECTIVE
In metastatic colorectal cancer, a combination of leucovorin (LV) and fluorouracil (FU) with oxaliplatin (FOLFOX) 4 is a standard first-line regimen. The cumulative neurotoxicity of oxaliplatin often requires therapy to be stopped in patients who are still responding. This study evaluates a new strategy of intermittent oxaliplatin treatment that is based on FOLFOX7, a simplified leucovorin and fluorouracil regimen with high-dose oxaliplatin.


METHODS
Previously untreated patients were randomly assigned to either FOLFOX4 administered every 2 weeks until progression (arm A) or FOLFOX7 for six cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm B).


RESULTS
Six hundred twenty patients were enrolled, including an exploratory cohort of 95 elderly or poor prognosis patients. Median progression-free survival and survival times were 9.0 and 19.3 months, respectively, in patients allocated to arm A compared with 8.7 and 21.2 months, respectively, in patients allocated to arm B (P = not significant). Response rates were 58.5% with arm A and 59.2% with arm B. National Cancer Institute Common Toxicity Criteria grade 3 or 4 toxicity was observed in 54.4% of the patients in arm A v 48.7% of patients in arm B. From cycle 7, fewer patients experienced grade 3 or 4 toxicity in arm B. Grade 3 sensory neuropathy was observed in 17.9% of the patients in arm A v 13.3% of patients in arm B (P = .12). In arm B, oxaliplatin was reintroduced in only 40.1% of the patients but achieved responses or stabilizations in 69.4% of these patients.


CONCLUSIONS
Oxaliplatin can be safely stopped after six cycles in a FOLFOX regimen. Further study is needed to fully evaluate oxaliplatin reintroduction.
Tournigand
Christophe
C
Hôpital Saint-Antoine, Paris, France.
Cervantes
Andres
A
Figer
Arie
A
Lledo
Gérard
G
Flesch
Michel
M
Buyse
Marc
M
Mineur
Laurent
L
Carola
Elisabeth
E
Etienne
Pierre-Luc
PL
Rivera
Fernando
F
Chirivella
Isabel
I
Perez-Staub
Nathalie
N
Louvet
Christophe
C
André
Thierry
T
Tabah-Fisch
Isabelle
I
de Gramont
Aimery
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D020551:Pulse Therapy, Drug; D016019:Survival Analysis; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil