Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin

被引:108
作者
Zaanan, A. [1 ,2 ]
Cuilliere-Dartigues, P. [1 ,3 ]
Guilloux, A. [1 ]
Parc, Y. [1 ,4 ]
Louvet, C. [1 ,2 ]
de Gramont, A. [1 ,2 ]
Tiret, E. [4 ]
Dumont, S. [5 ]
Gayet, B. [6 ]
Validire, P. [7 ]
Flejou, J. -F. [1 ,3 ]
Duval, A. [1 ]
Praz, F. [1 ]
机构
[1] UPMC, INSERM, UMR S 938, St Antoine Res Ctr, F-75571 Paris 12, France
[2] Hop St Antoine, AP HP, Dept Med Oncol, Paris, France
[3] Hop St Antoine, AP HP, Dept Pathol, Paris, France
[4] Hop St Antoine, AP HP, Dept Gen & Digest Surg, Paris, France
[5] UPMC, Inst Federatif Recherche65, F-75571 Paris 12, France
[6] Univ Paris 05, Dept Digest Dis Med Surg, Inst Mutualiste Montsouris, Paris, France
[7] Univ Paris 05, Dept Pathol, Inst Mutualiste Montsouris, Paris, France
关键词
chemotherapy; colon cancer; disease-free survival; microsatellite instability; oxaliplatin; p53; ADVANCED COLORECTAL-CANCER; SURGICAL ADJUVANT BREAST; DNA MISMATCH REPAIR; PROGNOSTIC VALUE; K-RAS; THYMIDYLATE SYNTHASE; RANDOMIZED-TRIAL; TP53; MUTATION; CHEMOTHERAPY; FLUOROURACIL;
D O I
10.1093/annonc/mdp383
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The aim was to determine the values of p53 tumour expression and microsatellite instability (MSI) phenotype to predict benefit from adjuvant chemotherapy of colon cancer by 5-fluorouracil and leucovorin (FL) alone or with oxaliplatin (FOLFOX). Patients and methods: This retrospective study included 233 unselected patients with stage III colon cancer treated by FL (n = 124) or FOLFOX (n = 109). The impact of p53 expression and MSI on disease-free survival (DFS) was defined using univariate and multivariate analyses. A Cox proportional hazards model was specifically designed to evaluate the interaction between chemotherapy and these genetic alterations. Results: In univariate analyses, addition of oxaliplatin significantly improved DFS provided that tumour overexpressed p53 [hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.19-0.82; P = 0.01] or displayed MSI phenotype (HR 0.17; 95% CI 0.04-0.68; P = 0.01). In multivariate analyses, p53 was confirmed as an independent factor predictive of benefit from FOLFOX (P = 0.03), while the interaction of MSI with chemotherapy could not be determined in the absence of relapse in the MSI group treated with FOLFOX. Conclusion: Our observations indicate that MSI status and p53 expression may influence the impact of oxaliplatin on adjuvant treatment of stage III colon cancer patients.
引用
收藏
页码:772 / 780
页数:9
相关论文
共 43 条
[1]   Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes' B and C colon cancer:: A national cancer institute-national surgical adjuvant breast and bowel project collaborative study [J].
Allegra, CJ ;
Paik, S ;
Colangelo, LH ;
Parr, AL ;
Kirsch, I ;
Kim, G ;
Klein, P ;
Johnston, PG ;
Wolmark, N ;
Wieand, HS .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (02) :241-250
[2]   Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer [J].
Andre, T ;
Boni, C ;
Mounedji-Boudiaf, L ;
Navarro, M ;
Tabernero, J ;
Hickish, T ;
Topham, C ;
Zaninelli, M ;
Clingan, P ;
Bridgewater, J ;
Tabah-Fisch, I ;
de Gramont, A .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (23) :2343-2351
[3]   Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer:: Results of a randomized trial [J].
André, T ;
Colin, P ;
Louvet, C ;
Gamelin, E ;
Bouche, O ;
Achille, E ;
Colbert, N ;
Boaziz, C ;
Piedbois, P ;
Tubiana-Mathieu, N ;
Boutan-Laroze, A ;
Flesch, M ;
Buyse, M ;
de Gramont, A .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (15) :2896-2903
[4]   EVALUATION OF 6 ANTIBODIES FOR IMMUNOHISTOCHEMISTRY OF MUTANT P53 GENE-PRODUCT IN ARCHIVAL COLORECTAL NEOPLASMS [J].
BAAS, IO ;
MULDER, JWR ;
OFFERHAUS, GJA ;
VOGELSTEIN, B ;
HAMILTON, SR .
JOURNAL OF PATHOLOGY, 1994, 172 (01) :5-12
[5]   Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes [J].
Berger, AC ;
Sigurdson, ER ;
LeVoyer, T ;
Hanlon, A ;
Mayer, RJ ;
Macdonald, JS ;
Catalano, PJ ;
Haller, DG .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (34) :8706-8712
[6]   Characterization of p53 wild-type and null isogenic colorectal cancer cell lines resistant to 5-fluorouracil, oxaliplatin, and irinotecan [J].
Boyer, J ;
McLean, EG ;
Aroori, S ;
Wilson, P ;
McCulla, A ;
Carey, PD ;
Longley, DB ;
Johnston, PG .
CLINICAL CANCER RESEARCH, 2004, 10 (06) :2158-2167
[7]   Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer [J].
Carethers, JM ;
Smith, EJ ;
Behling, CA ;
Nguyen, L ;
Tajima, A ;
Doctolero, RT ;
Cabrera, BL ;
Goel, M ;
Arnold, CA ;
Miyai, K ;
Boland, CR .
GASTROENTEROLOGY, 2004, 126 (02) :394-401
[8]   A review of GERCOD trials of bimonthly leucovorin plus 5-fluorouracil 48-h continuous infusion in advanced colorectal cancer:: Evolution of a regimen [J].
de Gramont, A ;
Louvet, C ;
André, T ;
Tournigand, C ;
Krulik, M .
EUROPEAN JOURNAL OF CANCER, 1998, 34 (05) :619-626
[9]  
Des Guetz G, 2007, ANTICANCER RES, V27, P2715
[10]   Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer [J].
Elsaleh, H ;
Joseph, D ;
Grieu, F ;
Zeps, N ;
Spry, N ;
Iacopetta, B .
LANCET, 2000, 355 (9217) :1745-1750