Phase II study of an optimized 5-fluorouracil-oxaliplatin strategy (OPTIMOX2) with celecoxib in metastatic colorectal cancer: a GERCOR study.
BACKGROUND
Oxaliplatin stop and go in combination with leucovorin and 5-fluorouracil has been successfully used in a previous study (OPTIMOX1) in metastatic colorectal cancer (MCR). Celecoxib is an anti-cyclooxygenase-2 drug with anti-neoplastic properties. In the present study, celecoxib was evaluated in combination with FOLFOX7 regimen and as a single agent in maintenance therapy.


METHODS
This phase II study examined for previously untreated MCR patients the stop-and-go procedure [six cycles of folinic acid, 5FU and oxaliplatin (FOLFOX7) followed by chemotherapy-free intervals (CFIs) and reintroduction at progression] with continuous administration of celecoxib (800 mg/day).


RESULTS
Forty-four patients were included, 42 eligible: performance status (%) 0/1/2=45/40/15, median age 60 (31-76) years. Response rate (RR) was 43% (95% CI 28%-58%). Median progression-free survival (PFS) was 6 months; median overall survival was 15.8 months. Grade 3/4 toxicity criteria were neurotoxicity 9.5%, thrombocytopenia 21.4%, neutropenia 7.1%, diarrhea 7.1%, nausea 4.8% and vomiting 2.4%. Median CFI 1 (n=27) duration was 3.9 months (range 2-39 months).


CONCLUSIONS
With an acceptable safety profile, celecoxib combined with FOLFOX7 achieved RR and PFS in the lower range of that obtained with FOLFOX7 alone. These results indicate the lack of synergy between FOLFOX7 and celecoxib. PFS of 6 months appears lower than PFS obtained in OPTIMOX1 study with simplified LV5FU2 in maintenance therapy.
André
T
T
Hôpital Tenon, Department of Medical Oncology, Paris; GERCOR (French Oncology Research Group), Paris, France. Electronic address: thierry.andre@tnn.aphp.fr.
Tournigand
C
C
Hôpital Saint Antoine, Department of Medical Oncology, Paris; GERCOR (French Oncology Research Group), Paris, France.
Mineur
L
L
Clinique Sainte Catherine, Department of Medical Oncology, Avignon; GERCOR (French Oncology Research Group), Paris, France.
Fellague-Chebra
R
R
GERCOR (French Oncology Research Group), Paris, France.
Flesch
M
M
Hôpital Devron, Dijon; GERCOR (French Oncology Research Group), Paris, France.
Mabro
M
M
Hôpital Foch, Department of Medical Oncology, Suresnes; GERCOR (French Oncology Research Group), Paris, France.
Hebbar
M
M
Hôpital Huriez, Department of Internal Medicine, Lille; GERCOR (French Oncology Research Group), Paris, France.
Postel Vinay
S
S
Hôpital Tenon, Department of Medical Oncology, Paris.
Bidard
F C
FC
Hôpital Tenon, Department of Medical Oncology, Paris.
Louvet
C
C
Hôpital Saint Antoine, Department of Medical Oncology, Paris; GERCOR (French Oncology Research Group), Paris, France.
de Gramont
A
A
Hôpital Saint Antoine, Department of Medical Oncology, Paris; GERCOR (French Oncology Research Group), Paris, France.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D011720:Pyrazoles; D013449:Sulfonamides; D000077150:Oxaliplatin; D000068579:Celecoxib; D002955:Leucovorin; D005472:Fluorouracil