Stein et al. BMC Cancer 2012, 12:356 http://www.biomedcentral.com/1471-2407/12/356 capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol 2011, 22:2042–2048. 24. Gruenberger B, Tamandl D, Schueller J, Scheithauer W, Zielinski C, Herbst F, Gruenberger T: Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol 2008, 26:1830–1835. 25. Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, Belghiti J, Piedbois P, Guimbaud R, Nordlinger B, et al: Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol 2006, 24:4976–4982. 26. Langer B, Bleiberg H, Labianca R, et al: Fluorouracil (FU) plus l-leucovorin (l-LV) versus observation after potentially curative resection of liver or lung metastases from colorectal cancer (CRC): results of the ENG (EORTC/NCIC CTG/GIVIO) randomized trial. Proc Am Soc Clin Oncol 2002, 21(abstr 592):2002. 27. Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, Nitti D, Torri V, Elias D, O’Callaghan C, et al: Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 2008, 26:4906–4911. 28. Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, Shacham-Shmueli E, Rivera F, Kwok-Keung Choi C, Santoro A: A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol 2009, 20:1964–1970. 29. Andre T, Van Cutsem E: A multinational, randomized phase III study of bevacizumab (Bev) with FOLFOX4 or XELOX versus FOLFOX4 alone as adjuvant treatment for colon cancer (CC): Subgroup analyses from the AVANT trial. J Clin Oncol 2011, 29:abstr 3509. 30. Voest EE, Snoeren N: A randomized two-arm phase III study to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) versus CAPOX alone in post radical resection of patients with liver metastases of colorectal cancer. J Clin Oncol 2011, 29:abstr 3565. 31. Allegra CJ, Yothers G, O’Connell MJ, Sharif S, Petrelli NJ, Colangelo LH, Atkins JN, Seay TE, Fehrenbacher L, Goldberg RM, et al: 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. 32. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, et al: 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. 33. Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, et al: 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. 34. Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, et al: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008, 26:2013–2019. 35. Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, Idziaszczyk S, Harris R, Fisher D, Kenny SL, et al: 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. 36. Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M, Koralewski P: Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol 2011, 22:1535–1546. 37. Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino L, Benedetti G, Evangelista W, Fanchini L, et al: 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. Page 9 of 10 38. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 350:2335–2342. 39. Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, Mazier MA, Canon JL, Georgoulias V, Peeters M, et al: Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 2009, 20:1842–1847. 40. 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. 41. Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, Marshall J, Cohn A, McCollum D, Stella P, et al: 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. 42. Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, van Groeningen CJ, Sinnige HA, et al: Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 2009, 360:563–572. 43. Bajetta E, Celio L, Ferrario E, Di Bartolomeo M, Denaro A, Dotti K, Mancin M, Bajetta R, Colombo A, Pusceddu S: Capecitabine plus oxaliplatin and irinotecan regimen every other week: a phase I/II study in first-line treatment of metastatic colorectal cancer. Ann Oncol 2007, 18:1810–1816. 44. Ychou M, Viret F, Kramar A, Desseigne F, Mitry E, Guimbaud R, Delpero JR, Rivoire M, Quenet F, Portier G, Nordlinger B: Tritherapy with fluorouracil/ leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases. Cancer Chemother Pharmacol 2008, 62:195–201. 45. Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, Kakolyris S, Tsousis S, Kouroussis C, Vamvakas L, et al: 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. 46. Zarate R, Rodriguez J, Bandres E, Patino-Garcia A, Ponz-Sarvise M, Viudez A, Ramirez N, Bitarte N, Chopitea A, Gacia-Foncillas J: Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis. Br J Cancer 2010, 102:987–994. 47. Fornaro L, Vasile E, Masi G, Loupakis F, Baldi GG, Allegrini G, Salvatore L, Cremolini C, Cupini S, Cortesi E, et al: Outcome of Second-Line Treatment After First-Line Chemotherapy With the GONO FOLFOXIRI Regimen. Clin Colorectal Cancer 2012, 11:71–76. 48. Assenat E, Desseigne F, Thezenas S, Viret F, Mineur L, Kramar A, Samalin E, Portales F, Bibeau F, Crapez-Lopez E, et al: Cetuximab Plus FOLFIRINOX (ERBIRINOX) as first-line treatment for unresectable metastatic colorectal cancer: a phase II trial. Oncologist 2011, 16(11):1557–1564. 49. Bruera G, Santomaggio A, Cannita K, Baldi PL, Tudini M, De Galitiis F, Mancini M, Marchetti P, Antonucci A, Ficorella C, Ricevuto E: “Poker” association of weekly alternating 5-fluorouracil, irinotecan, bevacizumab and oxaliplatin (FIr-B/FOx) in first line treatment of metastatic colorectal cancer: a phase II study. BMC Cancer 2010, 10:567. 50. Trarbach T, Schuette J: Dose escalating study of 5-FU/folinic acid (FA)/ oxaliplatin/irinotecan (FOLFOXIRI) and cetuximab in first-line therapy of patients with metastatic colorectal cancer. J Clin Oncol 2009, 27:abstr e15025. 51. Ychou M, Desseigne F: Preliminary results of a multicentre phase II trial evaluating cetuximab in combination with FOLFIRINOX (LV5FU + Irinotecan + Oxaliplatin) as first line treatment of metastatic colorectal cancer (mCRC) patients. Gastrointestinal Cancers Symposium 2009, 2009 ((Abstract-No: 295):abstr. 450. 52. Masi G, Loupakis F, Salvatore L, Fornaro L, Cremolini C, Cupini S, Ciarlo A, Del Monte F, Cortesi E, Amoroso D, et al: Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol 2010, 11:845–852.