Reintroduction of oxaliplatin is associated with improved survival in advanced colorectal cancer.
OBJECTIVE
In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were randomly assigned to two different schedules of leucovorin, fluorouracil, and oxaliplatin that were administered until progression in the control arm or in a stop-and-go fashion in the experimental arm. The randomly assigned treatment groups did not differ significantly in terms of response rate, progression-free survival, and overall survival (OS). However, the impact of oxaliplatin reintroduction on OS was potentially masked by the fact that a large number of patients did not receive the planned oxaliplatin reintroduction or received oxaliplatin after second-line therapy in both treatment groups.


METHODS
A Cox model was fitted with all significant baseline factors plus time-dependent variables reflecting tumor progression, reintroduction of oxaliplatin, and use of second-line irinotecan. A shared frailty model was fitted with all significant baseline factors plus the number of lines of chemotherapy received by the patient and the percentage of patients with oxaliplatin reintroduction in the center. An adjusted hazard ratio (HR) was calculated for three reintroduction classes (1% to 20%, 21% to 40%, and > 40%), using centers with no reintroduction (0%) as the reference group.


RESULTS
Oxaliplatin reintroduction had an independent and significant impact on OS (HR = 0.56, P = .009). The percentage of patients with oxaliplatin reintroductions also had a significant impact on OS. Centers in which more than 40% of the patients were reintroduced had an adjusted HR for OS of 0.59 compared with centers in which no patient was reintroduced.


CONCLUSIONS
Oxaliplatin reintroduction is associated with improved survival in patients with advanced colorectal cancer.
Hôpital Saint-Antoine, Paris Cedex 12, France. aimery.de-gramont@sat.aphp.fr
Aimery
A
de Gramont
Marc
M
Buyse
Jose Cortinas
JC
Abrahantes
Tomasz
T
Burzykowski
Emmanuel
E
Quinaux
Andres
A
Cervantes
Arie
A
Figer
Gérard
G
Lledo
Michel
M
Flesch
Laurent
L
Mineur
Elisabeth
E
Carola
Pierre-Luc
PL
Etienne
Fernando
F
Rivera
Isabel
I
Chirivella
Nathalie
N
Perez-Staub
Christophe
C
Louvet
Thierry
T
André
Isabelle
I
Tabah-Fisch
Christophe
C
Tournigand
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin