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. PATIENTS AND 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). CONCLUSION 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.

[1]  C. Tournigand,et al.  Chemotherapy-free intervals (CFI) in patients with metastatic colorectal cancer (MRC). , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  S. Barni,et al.  Alternating versus continuous "FOLFIRI" in advanced colorectal cancer (ACC): A randomized "GISCAD" trial. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  L. Mineur,et al.  OPTIMOX2, a large randomized phase II study of maintenance therapy or chemotherapy-free intervals (CFI) after FOLFOX in patients with metastatic colorectal cancer (MRC). A GERCOR study. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  C. Alexopoulos,et al.  Continuous versus intermittent chemotherapy in metastatic colorectal cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  M. Dong OPTIMOX1:A Randomized Study of FOLFOX4 or FOLFOX7 with Oxaliplatin in A Stop-and-Go Fashion in Advanced Colorectal Cancer——A GERCOR Study , 2006 .

[6]  C. Tournigand,et al.  Oxaliplatin reintroduction in patients previously treated with leucovorin, fluorouracil and oxaliplatin for metastatic colorectal cancer. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  C. Tournigand,et al.  FOLFIRI Followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  Daniel J Sargent,et al.  A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  S. Fenwick,et al.  Cyclooxygenase-2 expression in colorectal cancer liver metastases , 2004, Clinical & Experimental Metastasis.

[10]  D. Kerr,et al.  Comparison of intermittent and continuous palliative chemotherapy for advanced colorectal cancer: a multicentre randomised trial , 2003, The Lancet.

[11]  Jilly F. Evans,et al.  Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice. , 2003, Cancer research.

[12]  Ahmedin Jemal,et al.  Cancer Statistics, 2002 , 2002, CA: a cancer journal for clinicians.

[13]  D. Kerr,et al.  Continuous vs intermittant chemotherapy for advanced colorectal cancer: preliminary results of the MRC cr06b randomised trial , 2001 .

[14]  C. Tournigand,et al.  Evaluation of oxaliplatin dose intensity in bimonthly leucovorin and 48-hour 5-fluorouracil continuous infusion regimens (FOLFOX) in pretreated metastatic colorectal cancer. Oncology Multidisciplinary Research Group (GERCOR). , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[15]  Jilly F. Evans,et al.  Chemoprevention of intestinal polyposis in the APCΔ716 mouse by rofecoxib, a specific cyclooxygenase-2 inhibitor , 2000, American Journal of Gastroenterology.

[16]  C. Wilson,et al.  Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  B. Levin,et al.  The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. , 2000, The New England journal of medicine.

[18]  K. Seibert,et al.  Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. , 2000, Cancer research.

[19]  V. Steele,et al.  Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. , 2000, Cancer research.

[20]  W. Ray,et al.  Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study. , 1999, Archives of internal medicine.

[21]  J. Morrow,et al.  Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. , 1997, The Journal of clinical investigation.

[22]  Bruno C. Hancock,et al.  Suppression of Intestinal Polyposis in Apc Δ716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX-2) , 1996, Cell.

[23]  D. Khayat,et al.  Chimiothérapie des cancers colorectaux , 1996 .

[24]  M. Kondo,et al.  Expression of cyclooxygenase-1 and -2 in human colorectal cancer. , 1995, Cancer research.

[25]  S. Piantadosi,et al.  Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. , 1993, The New England journal of medicine.

[26]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.