Evidence-based appraisal of the upfront treatment for unresectable metastatic colorectal cancer patients

World Journal of Gastroenterology

Volumn 19, Issue 46, 2013, Pages 8474-8488

  Aprile, Giuseppe ^a   Lutrino, Stefania Eufemia ^a   Ferrari, Laura ^a   Casagrande, Mariaelena ^a   Bonotto, Marta ^a   Ongaro, Elena ^a   Puglisi, Fabio ^a,b  

^a UNIVERSITY HOSPITAL OF UDINE   (Italy)

^b UNIVERSITY OF UDINE   (Italy)

Author keywords

Angiogenic inhibitors; Chemotherapy; Colorectal cancer; Epidermal growth factor receptor inhibitors; First line; Maintenance

Indexed keywords

ANTINEOPLASTIC AGENT; BEVACIZUMAB; CAPECITABINE; CAPECITABINE PLUS OXALIPLATIN; CEDIRANIB; CETUXIMAB; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; OXALIPLATIN; PANITUMUMAB; PLACEBO; REGORAFENIB;

ARTICLE; CANCER CHEMOTHERAPY; DISEASE COURSE; HUMAN; METASTATIC COLORECTAL CANCER; MULTIPLE CYCLE TREATMENT; NEOPLASM; NEUROTOXICITY; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); SURVIVAL RATE;

ANGIOGENIC INHIBITORS; CHEMOTHERAPY; COLORECTAL CANCER; EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITORS; FIRST-LINE; MAINTENANCE;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; COLORECTAL NEOPLASMS; EVIDENCE-BASED MEDICINE; GENETIC PREDISPOSITION TO DISEASE; HUMANS; INDIVIDUALIZED MEDICINE; MOLECULAR TARGETED THERAPY; MUTATION; PATIENT SELECTION; PHENOTYPE; PREDICTIVE VALUE OF TESTS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; RAS PROTEINS; TREATMENT OUTCOME;

EID: 84890406096     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v19.i46.8474     Document Type: Article

References (120)

1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013; 49: 1374-1403 PMID: 23485231 DOI: 10.1016/j.ejca.2012.12.027]
2. Chu E. An update on the current and emerging targeted agents in metastatic colorectal cancer. Clin Colorectal Cancer 2012; 11: 1-13 PMID: 21752724 DOI: 10.1016/j.clcc.2011.05.005]
3. Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Köhne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Tabernero J, Aderka D, Barroso S, Bodoky G, Douillard JY, El Ghazaly H, Gallardo J, Garin A, GlynneJones R, Jordan K, Meshcheryakov A, Papamichail D, Pfeiffer P, Souglakos I, Turhal S, Cervantes A. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol 2012; 23: 2479-2516 PMID: 23012255]
4. Heinemann V, Douillard JY, Ducreux M, Peeters M. Targeted therapy in metastatic colorectal cancer -an example of personalised medicine in action. Cancer Treat Rev 2013; 39: 592-601 PMID: 23375249 DOI: 10.1016/j.ctrv.2012.12.011]
5. Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crinò L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 2007; 25: 1670-1676 PMID: 17470860]
6. Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, Kakolyris S, Tsousis S, Kouroussis Ch, Vamvakas L, Kalykaki A, Samonis G, Mavroudis D, Georgoulias V. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer 2006; 94: 798-805 PMID: 16508637]
7. Ciardiello F, Bianco R, Damiano V, Fontanini G, Caputo R, Pomatico G, De Placido S, Bianco AR, Mendelsohn J, Tortora G. Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells. Clin Cancer Res 2000; 6: 3739-3747 PMID: 10999768]
8. Saltz LB, Lenz HJ, Kindler HL, Hochster HS, Wadler S, Hoff PM, Kemeny NE, Hollywood EM, Gonen M, Quinones M, Morse M, Chen HX. Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol 2007; 25: 4557-4561 PMID: 17876013]
9. Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, van Groeningen CJ, Sinnige HA, Richel DJ, Voest EE, Dijkstra JR, Vink-Börger ME, Antonini NF, Mol L, van Krieken JH, Dalesio O, Punt CJ. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 2009; 360: 563-572 PMID: 19196673 DOI: 10.1056/NEJMoa0808268]
10. Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, Marshall J, Cohn A, McCollum D, Stella P, Deeter R, Shahin S, Amado RG. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 2009; 27: 672-680 PMID: 19114685 DOI: 10.1200/JCO.2008.19.8135]
11. Marshall JL. Vascular Endothelial Growth Factor plus Epidermal Growth Factor Receptor Dual Targeted Therapy in Metastatic Colorectal Cancer: Synergy or Antagonism? J Oncol 2009; 2009: 937305 PMID: 20016807 DOI: 10.1155/2009/937305]
12. Falcone A, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, Trenta P, Tomasello G, Ronzoni M, Ciuffreda L, Zaniboni A, Tonini G, Buonadonna A, Valsuani C, Chiara S, Carlomagno C, Boni C, Marcucci L, Boni L, Loupakis F. FOLFOXIRI/bevacizumab (bev) vs FOLFIRI/bev as firstline treatment in unresectable metastatic colorectal cancer (mCRC) patients (pts): Results of the phase III TRIBE trial by GONO group. J Clin Oncol 2013; 31 (suppl): abstr 3505
13. Adam R, Bridgewater J, Chau I, Alfonso PG, Rivoire M, Lasserre S, Waterkamp D, Gruenberger T. O-0025randomised, phase 2 study (olivia) of bevacizumab plus mfolfox6 or folfoxiri in patients with initially unresectable colorectal cancer liver metastases. Ann Oncol 2013; 24 (suppl 4): iv21-iv21
14. Loupakis F, Schirripa M, Caparello C, Funel N, Pollina L, Vasile E, Cremolini C, Salvatore L, Morvillo M, Antoniotti C, Marmorino F, Masi G, Falcone A. Histopathologic evaluation of liver metastases from colorectal cancer in patients treated with FOLFOXIRI plus bevacizumab. Br J Cancer 2013; 108: 2549-2556 PMID: 23703247 DOI: 10.1038/bjc.2013.245]
15. Fornaro L, Lonardi S, Masi G, Loupakis F, Bergamo F, Salvatore L, Cremolini C, Schirripa M, Vivaldi C, Aprile G, Zaniboni A, Bracarda S, Fontanini G, Sensi E, Lupi C, Morvillo M, Zagonel V, Falcone A. FOLFOXIRI in combination with panitumumab as first-line treatment in quadruple wildtype (KRAS, NRAS, HRAS, BRAF) metastatic colorectal cancer patients: a phase II trial by the Gruppo Oncologico Nord Ovest (GONO). Ann Oncol 2013; 24: 2062-2067 PMID: 23666916 DOI: 10.1093/annonc/mdt165]
16. Garufi C, Torsello A, Tumolo S, Ettorre GM, Zeuli M, Campanella C, Vennarecci G, Mottolese M, Sperduti I, Cognetti F. Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial. Br J Cancer 2010; 103: 1542-1547 PMID: 20959822 DOI: 10.1038/sj.bjc.6605940]
17. Tejpar S, Celik I, Schlichting M, Sartorius U, Bokemeyer C, Van Cutsem E. Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol 2012; 30: 3570-3577 PMID: 22734028 DOI: 10.1200/JCO.2012.42.2592]
18. De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S, Frattini M, Piessevaux H, Van Cutsem E, O'Callaghan CJ, Khambata-Ford S, Zalcberg JR, Simes J, Karapetis CS, Bardelli A, Tejpar S. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA 2010; 304: 1812-1820 PMID: 20978259 DOI: 10.1001/jama.2010.1535]
19. Chen J, Ye Y, Sun H, Shi G. Association between KRAS codon 13 mutations and clinical response to anti-EGFR treatment in patients with metastatic colorectal cancer: results from a meta-analysis. Cancer Chemother Pharmacol 2013; 71: 265-272 PMID: 23090619 DOI: 10.1007/s00280-012-2005-9]
20. De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, SartoreBianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol 2010; 11: 753-762 PMID: 20619739 DOI: 10.1016/S1470-2045(10)70130-3]
21. Peeters M, Douillard JY, Van Cutsem E, Siena S, Zhang K, Williams R, Wiezorek J. Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: assessment as prognostic and predictive biomarkers of response to panitumumab. J Clin Oncol 2013; 31: 759-765 PMID: 23182985 DOI: 10.1200/JCO.2012.45.1492]
22. Loupakis F, Ruzzo A, Cremolini C, Vincenzi B, Salvatore L, Santini D, Masi G, Stasi I, Canestrari E, Rulli E, Floriani I, Bencardino K, Galluccio N, Catalano V, Tonini G, Magnani M, Fontanini G, Basolo F, Falcone A, Graziano F. KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer 2009; 101: 715-721 PMID: 19603018 DOI: 10.1038/sj.bjc.6605177]
23. Tian S, Simon I, Moreno V, Roepman P, Tabernero J, Snel M, van'T Veer L, Salazar R, Bernards R, Capella G. A combined oncogenic pathway signature of BRAF, KRAS and PI3KCA mutation improves colorectal cancer classification and cetuximab treatment prediction. Gut 2013; 62: 540-549 PMID: 22798500 DOI: 10.1136/gutjnl-2012-302423]
24. Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, Bencardino K, Cercek A, Chen CT, Veronese S, Zanon C, SartoreBianchi A, Gambacorta M, Gallicchio M, Vakiani E, Boscaro V, Medico E, Weiser M, Siena S, Di Nicolantonio F, Solit D, Bardelli A. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 2012; 486: 532-536 PMID: 22722830 DOI: 10.1038/nature11156]
25. Diaz LA, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, Vogelstein B. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 2012; 486: 537-540 PMID: 22722843 DOI: 10.1038/nature11219]
26. Tougeron D, Cortes U, Ferru A, Villalva C, Silvain C, Tourani JM, Levillain P, Karayan-Tapon L. Epidermal growth factor receptor (EGFR) and KRAS mutations during chemotherapy plus anti-EGFR monoclonal antibody treatment in metastatic colorectal cancer. Cancer Chemother Pharmacol 2013; 72: 397-403 PMID: 23765179 DOI: 10.1007/s00280-013-2211-0]
27. André T, Blons H, Mabro M, Chibaudel B, Bachet JB, Tournigand C, Bennamoun M, Artru P, Nguyen S, Ebenezer C, Aissat N, Cayre A, Penault-Llorca F, Laurent-Puig P, de Gramont A. Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study. Ann Oncol 2013; 24: 412-419 PMID: 23041588 DOI: 10.1093/annonc/mds465]
28. Molinari F, Felicioni L, Buscarino M, De Dosso S, Buttitta F, Malatesta S, Movilia A, Luoni M, Boldorini R, Alabiso O, Girlando S, Soini B, Spitale A, Di Nicolantonio F, Saletti P, Crippa S, Mazzucchelli L, Marchetti A, Bardelli A, Frattini M. Increased detection sensitivity for KRAS mutations enhances the prediction of anti-EGFR monoclonal antibody resistance in metastatic colorectal cancer. Clin Cancer Res 2011; 17: 4901-4914 PMID: 21632860 DOI: 10.1158/1078-0432. CCR-10-3137]
29. Wagner AD, Arnold D, Grothey AA, Haerting J, Unverzagt S. Anti-angiogenic therapies for metastatic colorectal cancer. Cochrane Database Syst Rev 2009; (3): CD005392 PMID: 19588372 DOI: 10.1002/14651858.CD005392.pub3]
30. Vale CL, Tierney JF, Fisher D, Adams RA, Kaplan R, Maughan TS, Parmar MK, Meade AM. Does anti-EGFR therapy improve outcome in advanced colorectal cancer? A systematic review and meta-analysis. Cancer Treat Rev 2012; 38: 618-625 PMID: 22118887 DOI: 10.1016/j.ctrv.2011.11.002]
31. Stintzing S, Fischer von Weikersthal L, Decker T, Vehling-Kaiser U, Jäger E, Heintges T, Stoll C, Giessen C, Modest DP, Neumann J, Jung A, Kirchner T, Scheithauer W, Heinemann V. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer-subgroup analysis of patients with KRAS: mutated tumours in the randomised German AIO study KRK-0306. Ann Oncol 2012; 23: 1693-1699 PMID: 22219013 DOI: 10.1093/annonc/mdr571]
32. Mansmann U, Sartorius U, Laubender R, Giessen C, Esser R, Heinemann V. O-0009quantitative analysis of the impact of deepness of response on post-progression survival time following first-line treatment in patients with mcrc[J]. Ann Oncol 2013; 24 (suppl 4): iv14-iv15
33. Sommeijer DW, Qian S, Meyers JP. Prognostic value of early objective tumor response (EOTR) to first-line systemic therapy in metastatic colorectal cancer (mCRC): Individual patient data (IPD) meta-analysis of randomized trials from the ARCADE database. J Clin Oncol 2013; 31 (suppl): abstr 3520
34. Multi-Line Therapy Trial in Unresectable Metastatic Colorectal Cancer (STRATEGIC-1), ClinicalTrials.gov identifier: NCT01910610. Available from: URL: http://clinicaltrials.gov/show/NCT01910610
35. Budinska E, Popovici V, Tejpar S, D'Ario G, Lapique N, Sikora KO, Di Narzo AF, Yan P, Hodgson JG, Weinrich S, Bosman F, Roth A, Delorenzi M. Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancer. J Pathol 2013; 231: 63-76 PMID: 23836465 DOI: 10.1002/path.4212]
36. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487: 330-337 PMID: 22810696 DOI: 10.1038/nature11252]
37. Popovici V, Budinska E, Tejpar S, Weinrich S, Estrella H, Hodgson G, Van Cutsem E, Xie T, Bosman FT, Roth AD, Delorenzi M. Identification of a poor-prognosis BRAFmutant-like population of patients with colon cancer. J Clin Oncol 2012; 30: 1288-1295 PMID: 22393095 DOI: 10.1200/ JCO.2011.39.5814]
38. Abajo A, Boni V, Lopez I, Gonzalez-Huarriz M, Bitarte N, Rodriguez J, Zarate R, Bandres E, Garcia-Foncillas J. Identification of predictive circulating biomarkers of bevacizumabcontaining regimen efficacy in pre-treated metastatic colorectal cancer patients. Br J Cancer 2012; 107: 287-290 PMID: 22699823 DOI: 10.1038/bjc.2012.242]
39. Custodio A, Feliu J. Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: beyond KRAS mutations. Crit Rev Oncol Hematol 2013; 85: 45-81 PMID: 22647972 DOI: 10.1016/j.critr evonc.2012.05.001]
40. Richman SD, Chambers P, Seymour MT, Daly C, Grant S, Hemmings G, Quirke P. Intra-tumoral heterogeneity of KRAS and BRAF mutation status in patients with advanced colorectal cancer (aCRC) and cost-effectiveness of multiple sample testing. Anal Cell Pathol (Amst) 2011; 34: 61-66 PMID: 21483104 DOI: 10.3233/ACP-2011-0005]
41. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012; 366: 883-892 PMID: 22397650 DOI: 10.1056/NEJMoa1113205]
42. Basik M, Aguilar-Mahecha A, Rousseau C, Diaz Z, Tejpar S, Spatz A, Greenwood CM, Batist G. Biopsies: nextgeneration biospecimens for tailoring therapy. Nat Rev Clin Oncol 2013; 10: 437-450 PMID: 23799370 DOI: 10.1038/nrclinonc.2013.101]
43. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 2013; 10: 472-484 PMID: 23836314 DOI: 10.1038/ nrclinonc.2013.110]
44. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy? Genet Med 2013; 15: 517-527 PMID: 23429431 DOI: 10.1038/gim.2012.184]
45. Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 2008; 26: 5705-5712 PMID: 19001320 DOI: 10.1200/JCO.2008.18.0786]
46. Valtorta E, Misale S, Sartore-Bianchi A, Nagtegaal ID, Paraf F, Lauricella C, Dimartino V, Hobor S, Jacobs B, Ercolani C, Lamba S, Scala E, Veronese S, Laurent-Puig P, Siena S, Tejpar S, Mottolese M, Punt CJ, Gambacorta M, Bardelli A, Di Nicolantonio F. KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Int J Cancer 2013; 133: 1259-1265 PMID: 23404247 DOI: 10.1002/ ijc.28106]
47. Fornaro L, Baldi GG, Masi G, Allegrini G, Loupakis F, Vasile E, Cupini S, Stasi I, Salvatore L, Cremolini C, Vincenzi B, Santini D, Tonini G, Graziano F, Ruzzo A, Canestrari E, Magnani M, Falcone A. Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: clinical outcome according to KRAS and BRAF mutational status. Crit Rev Oncol Hematol 2011; 78: 243-251 PMID: 20619672 DOI: 10.1016/j.critrevonc.2010.06.003]
48. Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A, Bernards R. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 2012; 483: 100-103 PMID: 22281684 DOI: 10.1038/nature10868]
49. De Roock W, De Vriendt V, Normanno N, Ciardiello F, Tejpar S. KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. Lancet Oncol 2011; 12: 594-603 PMID: 21163703 DOI: 10.1016/S1470-2045(10)70209-6]
50. Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 2011; 29: 2011-2019 PMID: 21502544 DOI: 10.1200/JCO.2010.33.5091]
51. Sartore-Bianchi A, Martini M, Molinari F, Veronese S, Nichelatti M, Artale S, Di Nicolantonio F, Saletti P, De Dosso S, Mazzucchelli L, Frattini M, Siena S, Bardelli A. PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 2009; 69: 1851-1857 PMID: 19223544 DOI: 10.1158/0008-5472. CAN-08-2466]
52. Sood A, McClain D, Maitra R, Basu-Mallick A, Seetharam R, Kaubisch A, Rajdev L, Mariadason JM, Tanaka K, Goel S. PTEN gene expression and mutations in the PIK3CA gene as predictors of clinical benefit to anti-epidermal growth factor receptor antibody therapy in patients with KRAS wild-type metastatic colorectal cancer. Clin Colorectal Cancer 2012; 11: 143-150 PMID: 22285706 DOI: 10.1016/j.clcc.2011.12.001]
53. Loupakis F, Pollina L, Stasi I, Ruzzo A, Scartozzi M, Santini D, Masi G, Graziano F, Cremolini C, Rulli E, Canestrari E, Funel N, Schiavon G, Petrini I, Magnani M, Tonini G, Campani D, Floriani I, Cascinu S, Falcone A. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J Clin Oncol 2009; 27: 2622-2629 PMID: 19398573 DOI: 10.1200/JCO.2008.20.2796]
54. Mao C, Liao RY, Chen Q. Loss of PTEN expression predicts resistance to EGFR-targeted monoclonal antibodies in patients with metastatic colorectal cancer. Br J Cancer 2010; 102: 940 PMID: 20160728 DOI: 10.1038/sj.bjc.6605575]
55. Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369: 1023-1034 PMID: 24024839 DOI: 10.1056/NEJMoa1305275]
56. Schwartzberg LS, Rivera F, Karthaus M, Fasola G, Canon JL, Yu H, Oliner KS, Go WY. Analysis of KRAS/NRAS mutations in PEAK: A randomized phase II study of FOLFOX6 plus panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC). J Clin Oncol 2013; 31 (suppl): abstr 3631
57. Patterson SD, Peeters M, Siena S, Van Cutsem E, Humblet Y, Van Laethem JL, Andre T, Tian Y, Sidhu R, Oliner KS. Comprehensive analysis of KRAS and NRAS mutations as predictive biomarkers for single agent panitumumab (pmab) response in a randomized, phase III metastatic colorectal cancer (mCRC) study (20020408). J Clin Oncol 2013; 31 (suppl): abstr 3617
58. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 1626-1634 PMID: 18316791 DOI: 10.1200/JCO.2007.14.7116]
59. Giuliani F, De Vita F, Colucci G, Pisconti S. Maintenance therapy in colon cancer. Cancer Treat Rev 2010; 36 Suppl 3: S42-S45 PMID: 21129609 DOI: 10.1016/S0305-7372(10)70019-0]
60. Díaz-Rubio E, Gómez-España A, Massutí B, Sastre J, Abad A, Valladares M, Rivera F, Safont MJ, Martínez de Prado P, Gallén M, González E, Marcuello E, Benavides M, Fernández-Martos C, Losa F, Escudero P, Arrivi A, Cervantes A, Dueñas R, López-Ladrón A, Lacasta A, Llanos M, Tabernero JM, Antón A, Aranda E. First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. Oncologist 2012; 17: 15-25 PMID: 22234633 DOI: 10.1634/theoncologist.2011-0249]
61. Tournigand C, Samson B, Scheithauer W, Louvet C, Andre T, Lledo G, Latreille J, Viret F, Chibaudel B, de Gramont A. mFOLFOX-bevacizumab or XELOX-bevacizumab then bevacizumab (B) alone or with erlotinib (E) in first-line treatment of patients with metastatic colorectal cancer (mCRC): Interim safety analysis of DREAM study. J Clin Oncol 2009; 27 (15S): 4077
62. Wasan H, Adams RA, Wilson RH, Pugh C, Fisher D, Madi A, Sizer B, Butler R, Meade AM, Maughan T. Intermittent chemotherapy (CT) plus continuous or intermittent cetuximab (C) in the first-line treatment of advanced colorectal cancer (aCRC): Results of the two-arm phase II randomized MRC COIN-b trial. J Clin Oncol 2012; 30 (suppl 4): abstr 536
63. Tournigand C, Chibaudel B, Samson B, Scheithauer W, Lledo G, Viret F, André T, Jean Ramée F, Tubiana-Mathieu N, Dauba J, Dupuis O, Rinaldi Y, Mabro M, Aucoin N, Khalil A, Latreille J, Louvet C, Brusquant D, Bonnetain F, de Gramont A, GERCOR. Maintenance therapy with bevacizumab with or without erlotinib in metastatic colorectal cancer (mCRC) according to KRAS: results of the GERCOR DREAM phase III trial. J Clin Oncol 2013; 31 (suppl): abstr 3515
64. Johnsson A, Hagman H, Frödin JE, Berglund A, Keldsen N, Fernebro E, Sundberg J, De Pont Christensen R, Garm Spindler KL, Bergström D, Jakobsen A. A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial. Ann Oncol 2013; 24: 2335-2341 PMID: 23788755]
65. Koeberle D, Betticher D, von Moos R, Dietrich D, Brauchli P, Baertschi L, Matter-Walstra K, Winterhalder R, Borner M, Anchisi S, Moosmann P, Kollar A, Saletti P, Roth A, Frueh M, Kueng M, Popescu R, Schacher S, Hess V, Herrmann R. Bevacizumab continuation vs no continuation after firstline chemo-bevacizumab therapy in patients with metastatic colorectal cancer: a phase 3 non-inferiority trial. Ann Oncol 2013; 24: iv22
66. Koopman M, Simkens LHJ, Ten Tije AJ, Creemers GJ, Loosveld OJL, de Jongh FE, Erdkamp F, Erjavec Z, van der Torren AME, Van der Hoeven JJM, Nieboer P, Braun JJ, Jansen RL, Haasjes JG, Cats A, Wals JJ, Mol L, Dalesio O, Harm van Tinteren, Punt CJA. First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. J Clin Oncol 2013; 31 (suppl); abstr 3502
67. Grothey A, Sugrue MM, Purdie DM, Dong W, Sargent D, Hedrick E, Kozloff M. Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J Clin Oncol 2008; 26: 5326-5334 PMID: 18854571 DOI: 10.1200/JCO.2008.16.3212]
68. Bendell JC, Bekaii-Saab TS, Cohn AL, Hurwitz HI, Kozloff M, Tezcan H, Roach N, Mun Y, Fish S, Flick ED, Dalal D, Grothey A. Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOX-bevacizumab or FOLFIRI-bevacizumab: results from ARIES, a bevacizumab observational cohort study. Oncologist 2012; 17: 1486-1495 PMID: 23015662 DOI: 10.1634/ theoncologist.2012-0190]
69. Bennouna J, Sastre J, Arnold D, Österlund P, Greil R, Van Cutsem E, von Moos R, Viéitez JM, Bouché O, Borg C, Steffens CC, Alonso-Orduña V, Schlichting C, Reyes-Rivera I, Bendahmane B, André T, Kubicka S. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 2013; 14: 29-37 PMID: 23168366 DOI: 10.1016/S1470-2045(12)70477-1]
70. Salvatore L, Masi G, Loupakis F, Cremolini C, Schirripa M, Fornaro L, Granetto C, Miraglio E, Di Costanzo F, Antonuzzo L, Marcucci L, Cupini S, Boni C, Banzi M, Chiara S, Garbarino D, Valsuani C, Bonetti A, Boni L, Falcone A. Bevacizumab beyond progression in metastatic colorectal cancer patients receiving a fisrt-line treatment containing bevacizumab: update of BEBYP trial by GONO. Ann Oncol 2013; 24 (suppl 4): iv22 DOI: 10.1093/annonc/mdt201.27]
71. Van Cutsem E, Tabernero J, Lakomy R, Prenen H, Prausová J, Macarulla T, Ruff P, van Hazel GA, Moiseyenko V, Ferry D, McKendrick J, Polikoff J, Tellier A, Castan R, Allegra C. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012; 30: 3499-3506 PMID: 22949147]
72. Aprile G, Macerelli M, Giuliani F. Regorafenib for gastrointestinal malignancies: from preclinical data to clinical results of a novel multi-target inhibitor. BioDrugs 2013; 27: 213-224 PMID: 23435872 DOI: 10.1007/s40259-013-0014-9]
73. Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303-312 PMID: 23177514 DOI: 10.1016/S01406736(12)61900-X]
74. Loupakis F, Cremolini C, Yang D, Salvatore L, Zhang W, Wakatsuki T, Bohanes P, Schirripa M, Benhaim L, Lonardi S, Antoniotti C, Aprile G, Graziano F, Ruzzo A, Lucchesi S, Ronzoni M, De Vita F, Tonini G, Falcone A, Lenz HJ. Prospective validation of candidate SNPs of VEGF/VEGFR pathway in metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab. PLoS One 2013; 8: e66774 PMID: 23861747 DOI: 10.1371/journal.pone.0066774]
75. Scartozzi M, Giampieri R, Maccaroni E, Del Prete M, Faloppi L, Bianconi M, Galizia E, Loretelli C, Belvederesi L, Bittoni A, Cascinu S. Pre-treatment lactate dehydrogenase levels as predictor of efficacy of first-line bevacizumab-based therapy in metastatic colorectal cancer patients. Br J Cancer 2012; 106: 799-804 PMID: 22315053 DOI: 10.1038/bjc.2012.17]
76. Hurwitz HI, Tebbutt NC, Kabbinavar F, Giantonio BJ, Guan ZZ, Mitchell L, Waterkamp D, Tabernero J. Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist 2013; 18: 1004-1012 PMID: 23881988]
77. Manzoni M, Mariucci S, Delfanti S, Rovati B, Ronzoni M, Loupakis F, Brugnatelli S, Tinelli C, Villa E, Falcone A, Danova M. Circulating endothelial cells and their apoptotic fraction are mutually independent predictive biomarkers in Bevacizumab-based treatment for advanced colorectal cancer. J Cancer Res Clin Oncol 2012; 138: 1187-1196 PMID: 22419441 DOI: 10.1007/s00432-012-1190-6]
78. Vincenzi B, Zoccoli A, Schiavon G, Iuliani M, Pantano F, Dell'Aquila E, Ratta R, Muda AO, Perrone G, Brunelli C, Correale P, Riva E, Russo A, Loupakis F, Falcone A, Santini D, Tonini G. Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients. Eur J Cancer 2013; 49: 1501-1508 PMID: 23266047 DOI: 10.1016/j.ejca.2012.11.014]
79. Tournigand C, André T, Achille E, Lledo G, Flesh M, MeryMignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22: 229-237 PMID: 14657227]
80. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-2342 PMID: 15175435]
81. Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmueller J, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Mueller S, Schaefer B, Paul Modest DP, Jung A, Stintzing S. Randomized comparison of FOLFIRI plus cetuximab vs FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3). J Clin Oncol 2013; 31 (suppl): abstr LBA3506
82. Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360: 1408-1417 PMID: 19339720 DOI: 10.1056/NEJMoa0805019]
83. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25: 1539-1544 PMID: 17442997]
84. Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359: 1757-1765 PMID: 18946061 DOI: 10.1056/NEJMoa0804385]
85. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351: 337-345 PMID: 15269313]
86. Santini D, Vincenzi B, Addeo R, Garufi C, Masi G, Scartozzi M, Mancuso A, Frezza AM, Venditti O, Imperatori M, Schiavon G, Bronte G, Cicero G, Recine F, Maiello E, Cascinu S, Russo A, Falcone A, Tonini G. Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance? Ann Oncol 2012; 23: 2313-2318 PMID: 22396447 DOI: 10.1093/annonc/mdr623]
87. Wadlow RC, Hezel AF, Abrams TA, Blaszkowsky LS, Fuchs CS, Kulke MH, Kwak EL, Meyerhardt JA, Ryan DP, Szymonifka J, Wolpin BM, Zhu AX, Clark JW. Panitumumab in patients with KRAS wild-type colorectal cancer after progression on cetuximab. Oncologist 2012; 17: 14 PMID: 22210091 DOI: 10.1634/theoncologist.2011-0452]
88. Ciardiello F, Maiello E, Pisconti S, Giuliani F, Barone C, Rizzo M, Bordonaro R, Montesarchio V, Cinieri S, Martinelli E, Troiani T, Delcuratolo S, Simone G, Normanno N, Febbraro A, Tonini G, Colucci G. Optimal treatment strategy in KRAS wild type (wt) metastatic colorectal cancer (mCRC): Cetuximab plus FOLFIRI followed by FOLFOX4 with or without cetuximab-The Capri trial from the Gruppo Oncologico Dell' Italia Meridionale (GOIM). J Clin Oncol 2013; 31 (suppl); abstr e14565
89. Schmoll HJ, Cunningham D, Sobrero A, Karapetis CS, Rougier P, Koski SL, Kocakova I, Bondarenko I, Bodoky G, Mainwaring P, Salazar R, Barker P, Mookerjee B, Robertson J, Van Cutsem E. Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: a double-blind, randomized phase III study (HORIZON III). J Clin Oncol 2012; 30: 3588-3595 PMID: 22965961 DOI: 10.1200/JCO.2012.42.5355]
90. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 2010; 28: 4697-4705 PMID: 20921465 DOI: 10.1200/JCO.2009.27.4860]
91. Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, Idziaszczyk S, Harris R, Fisher D, Kenny SL, Kay E, Mitchell JK, Madi A, Jasani B, James MD, Bridgewater J, Kennedy MJ, Claes B, Lambrechts D, Kaplan R, Cheadle JP. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 2011; 377: 2103-2114 PMID: 21641636 DOI: 10.1016/ S0140-6736(11)60613-2]
92. Maindrault-Goebel F, Tournigand C, André T, Carola E, Mabro M, Artru P, Louvet C, de Gramont A. Oxaliplatin reintroduction in patients previously treated with leucovorin, fluorouracil and oxaliplatin for metastatic colorectal cancer. Ann Oncol 2004; 15: 1210-1214 PMID: 15277260]
93. Koopman M, Simkens LHJ, Ten Tije AJ, Creemers GJ, Loosveld OJL, de Jongh FE, Erdkamp F, Erjavec Z, van der Torren AME, Van der Hoeven JJM, Nieboer P, Braun JJ, Jansen RL, Haasjes JG, Cats A, Wals JJ, Mol L, Dalesio O, van Tinteren H, Punt CJA. Maintenance treatment with capecitabine and bevacizumab vs observation after induction treatment with chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC): The phase III CAIRO3 study of the Dutch Colorectal Cancer Group (DCCG). J Clin Oncol 2013; 31 (suppl): abstr 3502
94. Saunders MP, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin D, Jonker DJ, Osborne S, Loeffler M, Waterkamp D, Cunningham D. Efficacy and safety according to age subgroups in AVEX, a randomized phase III trial of bevacizumab in combination with capecitabine for the first-line treatment of elderly patients with metastatic colorectal cancer. J Clin Oncol 2013; 31 (suppl): abstr 3521
95. Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kröning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J, Burris HA. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 2311-2319 PMID: 18390971 DOI: 10.1200/JCO.2007.13.1193]
96. Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 2010; 28: 4706-4713 PMID: 20921462 DOI: 10.1200/JCO.2009.27.6055]
97. Seymour MT, Brown SR, Middleton G, Maughan T, Richman S, Gwyther S, Lowe C, Seligmann JF, Wadsley J, Maisey N, Chau I, Hill M, Dawson L, Falk S, O'Callaghan A, Benstead K, Chambers P, Oliver A, Marshall H, Napp V, Quirke P. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol 2013; 14: 749-759 PMID: 23725851 DOI: 10.1016/S1470-2045(13)70163-3]
98. André 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. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004; 350: 2343-2351 PMID: 15175436]
99. A Randomized, Open-label Study of the Effect of Intermittent Xeloda in Combination With Eloxatin, Vs Fluorouracil/Leucovorin, on Disease-free Survival in Patients Who Have Undergone Surgery for Colon Cancer. [NCT00069121]. Available from: URL: http://clinicaltrials.gov/show/NCT00069121
100. Kidwell KM, Yothers G, Ganz PA, Land SR, Ko CY, Cecchini RS, Kopec JA, Wolmark N. Long-term neurotoxicity effects of oxaliplatin added to fluorouracil and leucovorin as adjuvant therapy for colon cancer: results from National Surgical Adjuvant Breast and Bowel Project trials C-07 and LTS-01. Cancer 2012; 118: 5614-5622 PMID: 22569841 DOI: 10.1002/cncr.27593]
101. O'Connell MJ, Campbell ME, Goldberg RM, Grothey A, Seitz JF, Benedetti JK, André T, Haller DG, Sargent DJ. Survival following recurrence in stage II and III colon cancer: findings from the ACCENT data set. J Clin Oncol 2008; 26: 2336-2341 PMID: 18467725 DOI: 10.1200/JCO.2007.15.8261]
102. Argyriou AA, Velasco R, Briani C, Cavaletti G, Bruna J, Alberti P, Cacciavillani M, Lonardi S, Santos C, Cortinovis D, Cazzaniga M, Kalofonos HP. Peripheral neurotoxicity of oxaliplatin in combination with 5-fluorouracil (FOLFOX) or capecitabine (XELOX): a prospective evaluation of 150 colorectal cancer patients. Ann Oncol 2012; 23: 3116-3122 PMID: 22865779 DOI: 10.1093/annonc/mds208]
103. Hoff PM, Saad ED, Costa F, Coutinho AK, Caponero R, Prolla G, Gansl RC. Literature review and practical aspects on the management of oxaliplatin-associated toxicity. Clin Colorectal Cancer 2012; 11: 93-100 PMID: 22154408 DOI: 10.1016/j.clcc.2011.10.004]
104. Tofthagen C, Donovan KA, Morgan MA, Shibata D, Yeh Y. Oxaliplatin-induced peripheral neuropathy's effects on health-related quality of life of colorectal cancer survivors. Support Care Cancer 2013; 21: 3307-3313 PMID: 23903798]
105. Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Colangelo LH, Atkins JN, Seay TE, Fehrenbacher L, Goldberg RM, O'Reilly S, Chu L, Azar CA, Lopa S, Wolmark N. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol 2011; 29: 11-16 PMID: 20940184 DOI: 10.1200/ JCO.2010.30.0855]
106. Cavaletti G. Calcium and magnesium prophylaxis for oxaliplatin-related neurotoxicity: is it a trade-off between drug efficacy and toxicity? Oncologist 2011; 16: 1667-1668 PMID: 22128117 DOI: 10.1634/theoncologist.2011-0943]
107. Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC. Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility. Oncologist 2011; 16: 708-716 PMID: 21478275 DOI: 10.1634/theoncolo-gist.2010-0248]
108. Mols F, Beijers T, Lemmens V, van den Hurk CJ, Vreugdenhil G, van de Poll-Franse LV. Chemotherapy-induced neuropathy and its association with quality of life among 2to 11-year colorectal cancer survivors: results from the population-based PROFILES registry. J Clin Oncol 2013; 31: 2699-2707 PMID: 23775951 DOI: 10.1200/JCO.2013.49.1514]
109. de Gramont A, de Gramont A, Chibaudel B, Bachet JB, Larsen AK, Tournigand C, Louvet C, André T. From chemotherapy to targeted therapy in adjuvant treatment for stage III colon cancer. Semin Oncol 2011; 38: 521-532 PMID: 21810511 DOI: 10.1053/j.seminoncol.2011.05.006]
110. Cascinu S, Catalano V, Cordella L, Labianca R, Giordani P, Baldelli AM, Beretta GD, Ubiali E, Catalano G. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2002; 20: 3478-3483 PMID: 12177109]
111. Argyriou AA, Chroni E, Polychronopoulos P, Iconomou G, Koutras A, Makatsoris T, Gerolymos MK, Gourzis P, Assimakopoulos K, Kalofonos HP. Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced neuropathy. Neurology 2006; 67: 2253-2255 PMID: 17190958]
112. Durand JP, Deplanque G, Montheil V, Gornet JM, Scotte F, Mir O, Cessot A, Coriat R, Raymond E, Mitry E, Herait P, Yataghene Y, Goldwasser F. Efficacy of venlafaxine for the prevention and relief of oxaliplatin-induced acute neurotoxicity: results of EFFOX, a randomized, double-blind, placebocontrolled phase III trial. Ann Oncol 2012; 23: 200-205 PMID: 21427067 DOI: 10.1093/annonc/mdr045]
113. Knijn N, Tol J, Koopman M, Werter MJ, Imholz AL, Valster FA, Mol L, Vincent AD, Teerenstra S, Punt CJ. The effect of prophylactic calcium and magnesium infusions on the incidence of neurotoxicity and clinical outcome of oxaliplatinbased systemic treatment in advanced colorectal cancer patients. Eur J Cancer 2011; 47: 369-374 PMID: 21067912 DOI: 10.1016/j.ejca.2010.10.006]
114. Loprinzi CL, Qin R, Dakhil SR, Fehrenbacher L, Stella PJ, Atherton PJ, Seisler DK, Qamar R, Carlton Lewis G, Grothey A. Phase III randomized, placebo (PL)-controlled, double blindo f intravenous calcium/magnesium (CaMg) to prevent oxaliplatin-induced sensory neurotoxicity (sNT), N08CB: an alliance for clinical trials in oncology study. J Clin Oncol 2013; 31 (suppl): abstr 3501
115. Moreau LC, Rajan R, Thirlwell MP, Alcindor T. Response to chemotherapy in metastatic colorectal cancer after exposure to oxaliplatin in the adjuvant setting. Anticancer Res 2013; 33: 1765-1768 PMID: 23564831]
116. Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M, Mineur L, Carola E, Etienne PL, Rivera F, Chirivella I, Perez-Staub N, Louvet C, André T, Tabah-Fisch I, de Gramont A. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer--a GERCOR study. J Clin Oncol 2006; 24: 394-400 PMID: 16421419]
117. Adams RA, Meade AM, Seymour MT, Wilson RH, Madi A, Fisher D, Kenny SL, Kay E, Hodgkinson E, Pope M, Rogers P, Wasan H, Falk S, Gollins S, Hickish T, Bessell EM, Propper D, Kennedy MJ, Kaplan R, Maughan TS. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol 2011; 12: 642-653 PMID: 21641867 DOI: 10.1016/S1470-2045(11)70102-4]
118. Cunningham D, Lang I, Lorusso V, Ocvirk J, Shin D, Jonker DJ, Osborne S, Alexander Andre N, Waterkamp D, MP. Bevacizumab (bev) in combination with capecitabine (cape) for the first-line treatment of elderly patients with metastatic colorectal cancer (mCRC): Results of a randomized international phase III trial (AVEX). J Clin Oncol 2013; 31 (suppl): abstr 337
119. Tebbutt NC, Wilson K, Gebski VJ, Cummins MM, Zannino D, van Hazel GA, Robinson B, Broad A, Ganju V, Ackland SP, Forgeson G, Cunningham D, Saunders MP, Stockler MR, Chua Y, Zalcberg JR, Simes RJ, Price TJ. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol 2010; 28: 3191-3198 PMID: 20516443 DOI: 10.1200/ JCO.2009.27.7723]
120. Tveit KM, Guren T, Glimelius B, Pfeiffer P, Sorbye H, Pyrhonen S, Sigurdsson F, Kure E, Ikdahl T, Skovlund E, Fokstuen T, Hansen F, Hofsli E, Birkemeyer E, Johnsson A, Starkhammar H, Yilmaz MK, Keldsen N, Erdal AB, Dajani O, Dahl O, Christoffersen T. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 2012; 30: 1755-1762 PMID: 22473155 DOI: 10.1200/ JCO.2011.38.0915]