Top

Published in:

Open Access 01-12-2012 | Study protocol

Treatment with bevacizumab and FOLFOXIRI in patients with advanced colorectal cancer: presentation of two novel trials (CHARTA and PERIMAX) and review of the literature

Authors: Alexander Stein, Gabriel Glockzin, Andreas Wienke, Dirk Arnold, Thomas Edelmann, Bert Hildebrandt, Stephan Hollerbach, Gerald Illerhaus, Alfred Königsrainer, Michael Richter, Hans J Schlitt, Hans-Joachim Schmoll

Published in: BMC Cancer | Issue 1/2012

Abstract

Background

More than half of patients with colorectal cancer will develop metastatic disease either evident at the time of initial diagnosis or during their course of disease. Besides multidisciplinary management further treatment intensification is warranted to improve the still limited prognosis.

Methods/design

In these two multi-centre, randomized phase II trials, conducted in Germany, 380 patients with R0-resectable colorectal liver metastases (PERIMAX) and with unresectable, metastatic colorectal cancer (CHARTA) will be recruited. Patients previously untreated for metastatic disease with either synchronous or metachronous metastases are randomly assigned in a 1:1 ratio to resection of colorectal liver metastases followed by postoperative FOLFOX for 6 months or perioperative FOLFOXIRI and bevacizumab for 3 months pre- and postoperative and resection (PERIMAX), or to induction chemotherapy with FOLFOX and bevacizumab +/− irinotecan for a maximum of 6 months followed by maintenance treatment with fluoropyrimidine and bevacizumab. The primary objective of these trials is to evaluate the feasibility and efficacy of FOLFOXIRI and bevacizumab in metastatic colorectal cancer. Primary endpoint is failure free survival rate at 18 months in the PERIMAX trial and progression free survival rate at 9 months in CHARTA. Secondary objectives include efficacy, safety and tolerability.

Discussion

The CHARTA and PERIMAX trials are designed to evaluate the benefits and limitations of a highly active four-drug regimen in distinct treatment situations of metastatic CRC. Eligible patients are classified into resectable liver metastases to be randomized to perioperative treatment with FOLFOXIRI and bevacizumab or postoperative FOLFOX in the PERIMAX, or unresectable metastatic CRC to be randomized between FOLFOX and bevacizumab with or without irinotecan, stratified for clinical groups according to disease and patients’ characteristics in the CHARTA trial.

Trial registration

Clinical trial identifier CHARTA: NCT01321957, PERIMAX: NCT01540435

Available only for authorised users

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed

Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010, 127 (12): 2893-2917. 10.1002/ijc.25516.CrossRefPubMed

van der Pool AE, Damhuis RA, Ijzermans JN, de Wilt JH, Eggermont AM, Kranse R, Verhoef C: Trends in incidence, treatment and survival of patients with stage IV colorectal cancer: a population-based series. Colorectal Dis. 2012, 14: 56-61. 10.1111/j.1463-1318.2010.02539.x.CrossRefPubMed

Mantke R, Schmidt U, Wolff S, Kube R, Lippert H: Incidence of synchronous liver metastases in patients with colorectal cancer in relationship to clinico-pathologic characteristics. Results of a German prospective multicentre observational study. Eur J Surg Oncol. 2012, 38: 259-265. 10.1016/j.ejso.2011.12.013.CrossRefPubMed

Schmoll HJ, Sargent D: Single agent fluorouracil for first-line treatment of advanced colorectal cancer as standard?. Lancet. 2007, 370: 105-107. 10.1016/S0140-6736(07)61062-9.CrossRefPubMed

Van Cutsem E, Dicato M, Arber N, Berlin J, Cervantes A, Ciardiello F, De Gramont A, Diaz-Rubio E, Ducreux M, Geva R, et al: Molecular markers and biological targeted therapies in metastatic colorectal cancer: expert opinion and recommendations derived from the 11th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2009. Ann Oncol. 2010, 21 (uppl 6): vi1-10.PubMed

Schmiegel W, Pox C, Arnold D, Porschen R, Rodel C, Reinacher-Schick A: Colorectal carcinoma: the management of polyps, (neo)adjuvant therapy, and the treatment of metastases. Dtsch Arztebl Int. 2009, 106: 843-848.PubMedPubMedCentral

Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, Grothey A, Vauthey JN, Nagorney DM, McWilliams RR: Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009, 27: 3677-3683. 10.1200/JCO.2008.20.5278.CrossRefPubMedPubMedCentral

Morris EJ, Forman D, Thomas JD, Quirke P, Taylor EF, Fairley L, Cottier B, Poston G: Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg. 2010, 97: 1110-1118. 10.1002/bjs.7032.CrossRefPubMed

10.

Jonas S, Thelen A, Benckert C, Spinelli A, Sammain S, Neumann U, Rudolph B, Neuhaus P: Extended resections of liver metastases from colorectal cancer. World J Surg. 2007, 31: 511-521. 10.1007/s00268-006-0140-3.CrossRefPubMed

11.

Wei AC, Greig PD, Grant D, Taylor B, Langer B, Gallinger S: Survival after hepatic resection for colorectal metastases: a 10-year experience. Ann Surg Oncol. 2006, 13: 668-676. 10.1245/ASO.2006.05.039.CrossRefPubMed

12.

Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D’Angelica M: Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007, 25: 4575-4580. 10.1200/JCO.2007.11.0833.CrossRefPubMed

13.

Scheele J, Stang R, Altendorf-Hofmann A, Paul M: Resection of colorectal liver metastases. World J Surg. 1995, 19: 59-71. 10.1007/BF00316981.CrossRefPubMed

14.

Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999, 230: 309-318. 10.1097/00000658-199909000-00004. discussion 318–321CrossRefPubMedPubMedCentral

15.

Adam R, Barroso E: Impact of the type and modalities of preoperative chemotherapy on the outcome of liver resection for colorectal metastases. J Clin Oncol. 2011, 29: abstr 3519-

16.

de Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD, Choti MA, Aldrighetti L, Capussotti L, Pawlik TM: Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009, 250: 440-448.PubMed

17.

Nagashima I, Takada T, Nagawa H, Muto T, Okinaga K: Proposal of a new and simple staging system of colorectal liver metastasis. World J Gastroenterol. 2006, 12: 6961-6965.CrossRefPubMedPubMedCentral

18.

Poston GJ, Figueras J, Giuliante F, Nuzzo G, Sobrero AF, Gigot JF, Nordlinger B, Adam R, Gruenberger T, Choti MA, et al: Urgent need for a new staging system in advanced colorectal cancer. J Clin Oncol. 2008, 26: 4828-4833. 10.1200/JCO.2008.17.6453.CrossRefPubMed

19.

Van Cutsem E, Nordlinger B, Adam R, Kohne CH, Pozzo C, Poston G, Ychou M, Rougier P: Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006, 42: 2212-2221. 10.1016/j.ejca.2006.04.012.CrossRefPubMed

20.

Yamaguchi T, Mori T, Takahashi K, Matsumoto H, Miyamoto H, Kato T: A new classification system for liver metastases from colorectal cancer in Japanese multicenter analysis. Hepatogastroenterology. 2008, 55: 173-178.PubMed

21.

Nordlinger B, Van Cutsem E, Gruenberger T, Glimelius B, Poston G, Rougier P, Sobrero A, Ychou M: Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol. 2009, 20: 985-992. 10.1093/annonc/mdn735.CrossRefPubMed

22.

Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, et al: Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008, 371: 1007-1016. 10.1016/S0140-6736(08)60455-9.CrossRefPubMedPubMedCentral

23.

Wong R, Cunningham D, Barbachano Y, Saffery C, Valle J, Hickish T, Mudan S, Brown G, Khan A, Wotherspoon A, et al: A multicentre study of 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. 10.1093/annonc/mdq714.CrossRefPubMed

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. 10.1200/JCO.2007.13.7679.CrossRefPubMed

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. 10.1200/JCO.2006.06.8353.CrossRefPubMed

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. 10.1200/JCO.2008.17.3781.CrossRefPubMed

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. 10.1093/annonc/mdp236.CrossRefPubMed

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-CrossRef

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. 10.1200/JCO.2010.30.0855.CrossRefPubMed

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. 10.1200/JCO.2009.27.4860.CrossRefPubMed

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. 10.1200/JCO.2010.33.5091.CrossRefPubMed

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. 10.1200/JCO.2007.14.9930.CrossRefPubMed

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. 10.1016/S0140-6736(11)60613-2.CrossRefPubMedPubMedCentral

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. 10.1093/annonc/mdq632.CrossRefPubMed

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. 10.1200/JCO.2006.09.0928.CrossRefPubMed

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. 10.1056/NEJMoa032691.CrossRefPubMed

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. 10.1093/annonc/mdp233.CrossRefPubMed

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. 10.1200/JCO.2008.16.3212.CrossRefPubMed

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. 10.1200/JCO.2008.19.8135.CrossRefPubMed

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. 10.1056/NEJMoa0808268.CrossRefPubMed

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. 10.1093/annonc/mdm347.CrossRefPubMed

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. 10.1007/s00280-007-0588-3.CrossRefPubMed

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. 10.1038/sj.bjc.6603011.CrossRefPubMedPubMedCentral

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. 10.1038/sj.bjc.6605595.CrossRefPubMedPubMedCentral

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. 10.1016/j.clcc.2011.06.013.CrossRefPubMed

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. 10.1634/theoncologist.2011-0141.CrossRefPubMedPubMedCentral

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: 567-10.1186/1471-2407-10-567.CrossRefPubMedPubMedCentral

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. 10.1016/S1470-2045(10)70175-3.CrossRefPubMed

53.

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. 10.1038/sj.bjc.6605940.CrossRefPubMedPubMedCentral

54.

Falcone A, Loupakis F: FOLFOXIRI plus bevacizumab (BV) versus FOLFIRI plus BV as first-line treatment of metastatic colorectal cancer (MCRC): Preliminary safety results of the phase III randomized TRIBE study by the Gruppo Oncologico Nord-Ovest (GONO). J Clin Oncol. 2010, 28: abstr 3543-

55.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009, 45: 228-247. 10.1016/j.ejca.2008.10.026.CrossRefPubMed

56.

Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A: Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009, 27: 3109-3116. 10.1200/JCO.2008.20.6771.CrossRefPubMed

57.

Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ: Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer. J Clin Oncol. 2011, 29: 1465-1471. 10.1200/JCO.2010.33.6297.CrossRefPubMed

58.

Ratain MJ, Sargent DJ: Optimising the design of phase II oncology trials: the importance of randomisation. Eur J Cancer. 2009, 45: 275-280. 10.1016/j.ejca.2008.10.029.CrossRefPubMed

59.

Piessevaux H, Schlichting M: Early tumor shrinkage for the prediction of efficacy of cetuximab in metastatic colorectal cancer: analysis from the CRYSTAL study. Ann Oncol. 2010, 21: abstr. 596-

60.

Folprecht G, Gruenberger T, Bechstein WO, Raab HR, Lordick F, Hartmann JT, Lang H, Frilling A, Stoehlmacher J, Weitz J, et al: Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010, 11: 38-47. 10.1016/S1470-2045(09)70330-4.CrossRefPubMed

61.

Wasan H, Adams RA: 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: abstr 536-

62.

Adams RA, Meade AM, Seymour MT, Wilson RH, Madi A, Fisher D, Kenny SL, Kay E, Hodgkinson E, Pope M, et al: 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. 10.1016/S1470-2045(11)70102-4.CrossRefPubMedPubMedCentral

63.

Chibaudel B, Maindrault-Goebel F, Lledo G, Mineur L, Andre T, Bennamoun M, Mabro M, Artru P, Carola E, Flesch M, et al: Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study. J Clin Oncol. 2009, 27: 5727-5733. 10.1200/JCO.2009.23.4344.CrossRefPubMed

64.

Diaz-Rubio E, Gomez-Espana A, Massuti B, Sastre J, Abad A, Valladares M, Rivera F, Safont MJ, Martinez de Prado P, Gallen M, et al: 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. 10.1634/theoncologist.2011-0249.CrossRefPubMedPubMedCentral

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/12/356/prepub

Title: Treatment with bevacizumab and FOLFOXIRI in patients with advanced colorectal cancer: presentation of two novel trials (CHARTA and PERIMAX) and review of the literature
Authors: Alexander Stein
Gabriel Glockzin
Andreas Wienke
Dirk Arnold
Thomas Edelmann
Bert Hildebrandt
Stephan Hollerbach
Gerald Illerhaus
Alfred Königsrainer
Michael Richter
Hans J Schlitt
Hans-Joachim Schmoll
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-12-356

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods/design

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2012

Role of emmprin in endometrial cancer

SOXs in human prostate cancer: implication as progression and prognosis factors

Expression of proto-oncogene KIT is up-regulated in subset of human meningiomas

Prognostic impact of detecting viable circulating tumour cells in gastric cancer patients using a telomerase-specific viral agent: a prospective study

Regulation of interferon pathway in 2-methoxyestradiol-treated osteosarcoma cells

Diabetes, glucose control, glucose lowering medications, and cancer risk: A 10-year population-based historical cohort

Keynote webinar | Spotlight on antibody–drug conjugates in cancer