41
Views
16
CrossRef citations to date
0
Altmetric
Review

Beyond 5-fluorouracil: new horizons in systemic therapy for advanced colorectal cancer

, , &
Pages 607-628 | Published online: 11 Jul 2005

Bibliography

  • PARKIN DM: Global cancer statistics in the year 2000. Lancet Oncol (2001) 2:533–543.
  • SIMMONDS PC: Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. Br. Med. J. (2000) 321:531–535.
  • •A meta-analysis showing a benefit to palliative chemotherapy in advanced CRC.
  • Expectancy or primary chemotherapy in patients with advanced asymptomatic colorectal cancer: a randomized trial. Nordic Gastrointestinal Tumor Adjuvant Therapy Group. I Clin. Oncol (1992) 10:904–911.
  • SCHEITHAUER W, ROSEN H, KORNEK GV, SEBESTA C, DEPISCH D: Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BE Med. (1993) 306:752–755.
  • GLIMELIUS B, HOFFMAN K, GRAF W, PAHLMAN L, SJODEN PO: Quality of life during chemotherapy in patients with symptomatic advanced colorectal cancer. The Nordic Gastrointestinal Tumor Adjuvant Therapy Group. Cancer (1994) 73:556–562.
  • ACKLAND SP, MOORE M, JONES M et al.: A meta-analysis of two randomized trials of early chemotherapy in asymptomatic metastatic colorectal cancer. Proc. Am. Soc. Clin. Oncol (2001) 20:526.
  • Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced colorectal cancer meta-analysis project.Oncol (1992) 10:896–903.
  • POON MA, O'CONNELL MJ, MOERTEL CG et al: Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma../. Clin. Oncol (1989) 7:1407–1418.
  • PETRELLI N, DOUGLASS HO Jr, HERRERA L et al: The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized Phase III trial. Gastrointestinal Tumor Study Group. I Clin. Oncol (1989) 7:1419–1426.
  • DE GRAMONT A, BOSSET JF, MILAN C et al: Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J. Clin. Oncol (1997) 15:808–815.
  • ARDALAN B, CHUA L, TIAN EM et al.: A Phase II study of weekly 24-hour infusion with high-dose fluorouracil with leucovorin in colorectal carcinoma. J. Clin. Oncol (1991) 9:625–630.
  • KOHNE CH, WILS J, LORENZ M et al: Randomized Phase III study of high-dose fluorouracil given as a weekly 24-hour infusion with or without leucovorin versus bolus fluorouracil plus leucovorin in advanced colorectal cancer: European organization of Research and Treatment of Cancer Gastrointestinal Group Study 40952.1 Clin. Oncol (2003) 21:3721–3728.
  • O'CONNELL MJ: Current status of adjuvant therapy for colorectal cancer. Oncology (Huntingt) (2004) 18:751–755.
  • MINSKY BD: Combined modality therapy for rectal cancer. Cancer Chemother. Biol. Response ModiE (2003) 21:803–816.
  • VENOOK AP: Colorectal metastases confined to the liver: a unique opportunity? Semin. Oncol (2003) 30:34–39.
  • LIU G, FRANSSEN E, FITCH MI, WARNER E: Patient preferences for oral versus intravenous palliative chemotherapy. Oncol (1997) 15:110–115.
  • SCHILSKY RL, LEVIN J, WEST WH et al.: Randomized, open-label, Phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/ advanced colorectal cancer. J. Clin. Oncol (2002) 20:1519–1526.
  • VAN CUTSEM E, SORENSEN J, CASSIDY J et al: International Phase III study of oral eniluracil (EU) plus 5-Fluorouracil (5-FU) versus intravenous (IV) 5-FU plus leucovorin (LV) in the treatment of advanced colorectal cancer (ACC). Proc. Am. Soc. Clin. Oncol (2001) 20:522.
  • MIWA M, URA M, NISHIDAM et al: Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur. J. Cancer (1998) 34:1274–1281.
  • ISHIKAWA T, UTOH M, SAWADA N et al: Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts. Biochem. Pharmacol (1998) 55:1091–1097.
  • SCHULLER J, CASSIDY J, DUMONT E et al: Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother. Pharmacol (2000) 45:291–297.
  • HOFF PM, ANSARI R, BATIST G et al: Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized Phase III study. I Clin. Oncol (2001) 19:2282–92.
  • •A large Phase III trial showing the equivalence of capecitabine to bolus 5-FU/ LV.
  • VAN CUTSEM E, TWELVES C, CASSIDY J et al.: Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large Phase III study.' Clin. Oncol (2001) 19:4097–4106.
  • •A large Phase III trial showing the equivalence of capecitabine to bolus 5-FU/ LV.
  • TWELVES C, BOYER M, FINDLAY M et al: Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a Phase III trial conducted in patients with advanced colorectal carcinoma. Eur. I Cancer (2001) 37:597–604.
  • RAO S, CUNNINGHAM D, PRICE T et al: Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer. Br. Cancer (2004) 91:839–843.
  • RAO S, WATKINS D, HILL M et al: Capecitabine and mitomycin C (MMC) shows promising activity as a 3rd line agent in patients with metastatic colorectal carcinoma (IVICRC) resistant to 5FU and irinotecan. Proc. Am. Soc. Clin. Oncol. (2003) 22:320 (Abstract 1286).
  • MALET-MARTINO M, MARTINO R: Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review. Oncologist (2002) 7:288–323.
  • HO DH, PAZDUR R, COVINGTON W et al.: Comparison of 5-fluorouracil pharmacokinetics in patients receiving continuous 5-fluorouracil infusion and oral uracil plus Ni- (2'-tetrahydrofuryl) -5-fluorouracil. Clin. Cancer Res. (1998) 4:2085–2088.
  • YONEKURA K, BASAKI Y, CHIKAHISA L et UFT and its metabolites inhibit the angiogenesis induced by murine renal cell carcinoma, as determined by a dorsal air sac assay in mice. Clin. Cancer Res. (1999) 5:2185–2191.
  • BASAKI Y, CHIKAHISA L, AOYAGI K et al.: y-Hydroxybutyric acid and 5-fluorouracil, metabolites of UFT, inhibit the angiogenesis induced by vascular endothelial growth factor. Angiogenesis (2001) 4:163–173.
  • DOUILLARD JY, HOFF PM, SKILLINGS JR et al: Multicenter Phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer.Oncol. (2002) 20:3605–3616.
  • CARMICHAEL J, POPIELA T, RADSTONE D et al.: Randomized comparative study of tegafur/uracil and oral leucovorin versus parenteral fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer. Clin. Oncol. (2002) 20:3617–3627.
  • MacKAY HJ, HILL M, TWELVES C et al: A Phase I/II study of oral uracil/tegafur (UFT), leucovorin and irinotecan in patients with advanced colorectal cancer. Ann. Oncol. (2003) 14:1264–1269.
  • ALONSO V, ESCUDERO P, GRANDEZ R et al.: Weekly irinotecan (CPT-11) combined with uracil-tegafur (UFT) as first line treatment for metastatic colorectal carcinoma. Proc. Am. Soc. Clin. Oncol. (2003) 22:335 (Abstract 1344).
  • COHEN Y, SHULMAN K, IDELEVICH E et al: Irinotecan (CPT-11) combined with UFT as first line treatment of advanced colorectal carcinoma-A Phase II study. I Clin. Oncol. 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3742.
  • DOUILLARD JY, BENNOUNA J, ARTRU P et al.: UFT/LV combination based regimens with oxaliplatin or irinotecan as first line treatment for patients (pts) with non resectable metastatic colorectal cancer (IVICRC): results of two multicentric Phase II trials. J. Clin. Oncol. 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3545.
  • FELIU J, VICENT JM, GARCIA-GIRON C et al: Phase II study of UFT and oxaliplatin in first-line treatment of advanced colorectal cancer. Br. J. Cancer (2004) 91:1758–1762.
  • KIM K, NAME, LEE NS et al: Oxaliplatin and UFT combination chemotherapy in patients with metastatic colorectal cancer. Am. J. Clin. Oncol. (2002) 25:354–357.
  • ROSATI G, CORDIO S, TUCCI A et al: A Phase II trial of oxaliplatin (L-OHP) and uracil-tegafur (UFT)/folinic acid (FA) for advanced colorectal cancer (ACC) in elderly patients. I Clin. Oncol. 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3681.
  • RY00 HM, BAE SH, LEE HI et al.: Oxaliplatin, UFT and oral leucovorin combination chemotherapy in 5-fluorouracil refractory colorectal carcinoma: A Phase II study. I Clin. Oncol. 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3774.
  • PETRIOLI R, SABATINO M, FIASCHI Al et al.: UFT/leucovorin and oxaliplatin alternated with UFT/leucovorin and irinotecan in metastatic colorectal cancer. Br. J. Cancer (2004) 90:306–309.
  • SHIRASAKA T, SHIMAMATO Y, OHSHIMO H et al: Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs (1996) 7:548–557.
  • SUGIMACHI K, MAEHARA Y, HORIKOSHI N et al: An early Phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 Gastrointestinal Cancer Study Group. Oncology (1999) 57:202–210.
  • OHTSU A, BABA H, SAKATA Y et al: Phase II study of S-1, a novel oral fluorophyrimidine derivative, in patients with metastatic colorectal carcinoma. S-1 Cooperative Colorectal Carcinoma Study Group. Br. J. Cancer (2000) 83:141–145.
  • SHIRAO K, OHTSU A, TAKADA H et al.: Phase II study of oral S-1 for treatment of metastatic colorectal carcinoma. Cancer (2004) 100:2355–2361.
  • VAN DEN BRANDE J, SCHOFFSKI P, SCHELLENS JH et al: EORTC Early Clinical Studies Group early Phase II trial of S-1 in patients with advanced or metastatic colorectal cancer. BE J. Cancer (2003) 88:648–653.
  • JACKMAN AL, TAYLOR GA, GIBSON W et al.: ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study. Cancer Res. (1991) 51:5579–5586.
  • JACKMAN AL, FARRUGIA DC, GIBSON W et al.: ZD1694 (Tomudex): a new thymidylate synthase inhibitor with activity in colorectal cancer. Eur. J. Cancer (1995) 31A:1277–1282.
  • BEALE P, JUDSON I, HANWELL J et al:Metabolism, excretion and pharmacokinetics of a single dose of [14C]-raltitrexed in cancer patients. Cancer Chemother. Pharmacol. (1998) 42:71–76.
  • JUDSON I, MAUGHAN T, BEALE P et al.: Effects of impaired renal function on the pharmacokinetics of raltitrexed (Tomudex ZD-1694). Br. J. Cancer (1998) 78:1188–1193.
  • CUNNINGHAM D, ZALCBERG JR, RATH U et al.: Final results of a randomised trial comparing `Tomudex' (raltitrexed) with 5-fluorouracil plus leucovorin in advanced colorectal cancer. `Tomudex' Colorectal Cancer Study Group. Ann. Oncol. (1996) 7:961–965.
  • PAZDUR R, VINCENT M: Raltitrexed(Tomudex) versus 5-fluorouracil and leucovorin (5-FU + LV) in patients with advanced colorectal cancer (ACC): results of a randomized, multicenter, North American trial (Meeting abstract). Proc. Am. Soc. Clin. Oncol. (1997) 16:801.
  • COCCONI G, CUNNINGHAM D, VAN CUTSEM E et al: Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group. I Clin. Oncol. (1998) 16:2943-2952. 620 Expert Op/n. Investig. Drugs (2005) 14(6)54.
  • MAUGHAN TS, JAMES RD, KERR DJ et al: Comparison of survival, palliation, and quality of life with three chemotherapy regimens in metastatic colorectal cancer: a multicentre randomised trial. Lancet (2002) 359:1555–1563.
  • CORTINOVIS D, BAJETTA E, DI BARTOLOMEO M et al: Raltitrexed plus oxaliplatin in the treatment of metastatic colorectal cancer. Tumori. (2004) 90:186–191.
  • LAUDANI A, GEBBIA V, LEONARDI V et al.: Activity and toxicity of oxaliplatin plus raltitrexed in 5-fluorouracil refractory metastatic colorectal adeno-carcinoma. Anti-Cancer Res. (2004) 24:1139–42.
  • SANTINI D, MASSACESI C, DANGELILLO RM et al: Raltitrexed plus weekly oxaliplatin as first-line chemotherapy in metastatic colorectal cancer: a multicenter non-randomized Phase II study. Med. Oncol (2004) 21:59–66.
  • MARTONI A, MINI E, PINTO C et al.:Oxaliplatin plus raltitrexed in the treatment of patients with advanced colorectal cancer: a Phase II study. Anti-Cancer Res. (2003) 23:687–691.
  • SEITZ JF, BENNOUNA J, PAILLOT Bet al.: Multicenter non-randomized Phase II study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients. Ann. Oncol (2002) 13:1072–1079.
  • CASCINU S, GRAZIANO F, FERRAU F et al.: Raltitrexed plus oxaliplatin (TOMOX) as first-line chemotherapy for metastatic colorectal cancer. A Phase II study of the Italian Group for the Study of Gastrointestinal Tract Carcinomas (GISCAD). Ann. Oncol (2002) 13:716–720.
  • COMELLA P, CASARETTI R, CRUCITTA E et al: Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil iv. bolus: a salvage regimen for colorectal cancer patients. Br. I Cancer (2002) 86:1871–1875.
  • FELIU J, SALUD A, ESCUDERO P et al: Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a Phase II study. BE J. Cancer. (2004) 90:1502–7.
  • APARICIO J, VICENT JM, MAESTU Iet al.: Multicenter Phase II trial evaluating a three-weekly schedule of irinotecan plus raltitrexed in patients with 5-fluorouracil- refractory advanced colorectal cancer. Ann. Oncol (2003) 14:1121–1125.
  • CHIARA S, NOBILE MT, GOZZA A et al.: Irinotecan (I) and raltitrexed (R) in untreated advanced colorectal cancer patients: a Phase II study. Proc. Am. Soc. Oncol (2003) 22:315 (Abstract 1264).
  • CARNAGHI C, RIMASSA L, GARASSINO I et al: Irinotecan and raltitrexed: an active combination in advanced colorectal cancer. Ann. Oncol (2002) 13:1424–1429.
  • SHIH C, CHEN VJ, GOSSETT LS et al: LY231514, a pyrrolor2,3-dlpyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Res. (1997) 57:1116–1123.
  • WORZALLA JF, SHIH C, SCHULTZ RM: Role of folic acid in modulating the toxicity and efficacy of the multitargeted antifolate, LY231514. Anti-Cancer Res. (1998) 18:3235–3239.
  • BUNN P, PAOLETTI P, NIYIKIZA C et al: Vitamin B12 and folate reduce toxicity of AlimtaTm (pemetrexed disodium, LY231514, MTA), a novel antifolate/ antimetabolite. Proc. Am. Soc. Clin. Oncol (2001) 20 (Abstract 300).
  • HAMMOND LA, FORERO L, BEERAM M et al: Phase I study of pemetrexed (LY231514) with vitamin supplementation in patients with locally advanced or metastatic cancer. Proc. Am. Soc. Clin. Oncol (2003) 22:133 (Abstract 532).
  • CRIPPS C, BURNELL M, JOLI VET J et al.: Phase II study of first-line LY231514 (multi-targeted antifolate) in patients with locally advanced or metastatic colorectal cancer: an NCIC Clinical Trials Group study. Ann. Oncol (1999) 10:1175–1179.
  • JOHN W, PICUS J, BLANKE CD et al: Activity of multitargeted antifolate (pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma: results from a Phase II study. Cancer (2000) 88: 1807-1813.
  • PAULSON R, HAINSWORTH J, GEYER C et al.: A Phase II trial of MTA (multiple targeted antifolate, LY231514) in patients with 5-FU and irinotecan-refractory colorectal cancer (meeting abstract). Proc. Am. Soc. OM Oncol (1999) 18:1140.
  • RAYMOND E, LOUVET C, TOURNIGAND C et al.: Pemetrexed disodium combined with oxaliplatin, 5N38, or 5-fluorouracil, based on the quantitation of drug interactions in human HT29 colon cancer cells. Int. J. Oncol (2002) 21:361–367.
  • ATKINS JN, JACOBS S, WIEAND S et al: Pemetrexed and oxaliplatin for first-line treatment of patients with advanced colorectal cancer: A Phase II trial of the NSABP foundation research program. Proc. Am. Soc. Clin. Oncol (2003) 22:276 (Abstract 1108).
  • JACKMAN AL, KIMBELL R, AHERNE GW et al.: Cellular pharmacology and in vivo activity of a new anticancer agent, ZD9331: a water-soluble, nonpolyglutamatable, quinazoline-based inhibitor of thymidylate synthase. Cancer Res. (1997) 3:911–921.
  • SCHULZ J, KELLER A, CANFIELD V,PARKER G, DOUGLASS E: ZD-9331 as second- or third-line therapy in patients with advanced colorectal cancer: a Phase II multicenter trial. Am. J. Clin. Oncol (2004) 27:337–342.
  • LAVELLE F, BISSERY MC, ANDRE S, ROQUET F, RIOU JF: Preclinical evaluation of CPT-11 and its active metabolite SN-38. Semin. Oncol (1996) 23:11–20.
  • CUNNINGHAM D, PYRHÔNEN S, JAMES RD et al.: Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet. (1998) 352:1413–8.
  • •A Phase III trial showing the superiority of irinotecan over best supportive care in second-line therapy.
  • ROUGIER P, VAN CUTSEM E, BAJETTA E et al.: Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet (1998) 352:1407–1412.
  • •A Phase III trial showing superiority of irinotecan over infusional 5-FU as second-line therapy.
  • SALTZ LB, COX JV, BLANKE C et al: Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl. I Med. (2000) 343:905–914.
  • •A Phase III trial showing the superiority of bolus irinotecan/5-FU/LV over 5-FU/LV as first-line therapy.
  • DOUILLARD JY, CUNNINGHAM D, ROTH AD et al: Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet (2000) 355:1041–1047.
  • •A Phase III trial showing the superiority of irinotecan and infusional 5-FU/LV over 5-FU/LV in first-line therapy.
  • SARGENT DJ, NIEDZWIECKI D, O'CONNELL MJ, SCHILSKY RL: Recommendation for caution with irinotecan, fluorouracil, and leucovorin for colorectal cancer. N Engl. J. Med. (2001) 345:144–145.
  • ROTHENBERG ML, MEROPOL NJ, POPLIN EA, VAN CUTSEM E, WADLER S: Mortality associated with irinotecan plus bolus fluorouracili leucovorin: summary findings of an independent panel. J. Chi]. Oncol. (2001) 19:3801–7.
  • DELAUNOIT T, GOLDBERG RM, SARGENT DJ et al: Mortality associated with daily bolus 5-fluorouracilheucovorin administered in combination with either irinotecan or oxaliplatin: results from Intergroup trial N9741. Cancer (2004) 101:2170–2176.
  • KOHNE CH, VAN CUTSEM E, WILS JA et al.: Irinotecan improves the activity of the AIO regimen in metastatic colorectal cancer: Results of EORTC GI Group study 40986. Proc. Am. Soc. Clin. Oncol (2003) 22:254 (Abstract 1018).
  • RAYMOND E, FAIVRE S, WOYNAROWSKI JM, CHANEY SG: Oxaliplatin: mechanism of action and antineoplastic activity. Semi]. Oncol (1998) 25:4–12.
  • DE GRAMONT A, FIGER A, SEYMOUR M et al: Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J. Clin. Oncol (2000) 18:2938–2947.
  • •A large Phase III trial showing the superiority of oxaliplatin/5-FU/LV over 5-FU/LV.
  • GIACCHETTI S, PERPOINT B, ZIDANI R et al: Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer.Oncol (2000) 18:136–147.
  • GROTHEY A, DESCHLER B, KROENING H et al: Phase III study of bolus 5-fluorouracil (5-FU)/folinic acid (FA) (Mayo) versus weekly high-dose 24h 5-FU infusion/FA + oxaliplatin (OXA) (FUFOX) in advanced colorectal cancer (ACRC). Proc. Am. Soc. CM]. Oncol. (2002) 21: (Abstract 512).
  • HOSPERS G, SCHAAPVELD M: Phase III study of bolus 5-fluorouracil (5-FU)/ folinic acid versus high dose 24h 5-FU infusionifolinic acid (FA) + oxaliplatin (OXA) in metastatic colorectal cancer (MCRC). I Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:(Abstract 3539).
  • ROTHENBERG ML, OZA AM, BIGELOW RH et al.: Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a Phase III trial." Clin. Oncol (2003) 21:2059–2069.
  • GOLDBERG RM, SARGENT DJ, MORTON RF et al: A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. Oncol (2004) 22:23–30.
  • •A large Phase III trial comparing irinotecan and oxaliplatin combinations.
  • BAJETTA E, DI BARTOLOMEO M, MARIANI L et al: Randomized multicenter Phase II trial of two different schedules of irinotecan combined with capecitabine as first-line treatment in metastatic colorectal carcinoma. Cancer (2004) 100:279–287.
  • PARK SH, BANG SM, CHO EK et al: First-line chemotherapy with irinotecan plus capecitabine for advanced colorectal cancer. Oncology (2004) 66:353–357.
  • PATT YZ, LIEBMANN J, DIAMANDIDIS D et al: Capecitabine (X) Plus Irinotecan (XELIRI) as First Line Treatment for Metastatic Colorectal Cancer (MCRC): Final Safety Findings From a Phase II Trial. I Clin. Oncol. 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:(Abstract 3602).
  • MUNOZ A, SALUD A, ALONSO V et al: Final Analysis of Irinotecan (CPT-11) and Capecitabine (X) as First-line Treatment of Locally Advanced (LA) or Metastatic Colorectal Cancer (MCRC). j Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004)22:(Abstract 3610).
  • CARTWRIGHT TH, LOPEZ T, VUKELJA SJ, ENCARNACION C, BOEHM KA, ASMAR L: A Phase II Open-Label Study of Capecitabine in Combination With Irinotecan as First Line Treatment for Metastatic Colorectal Cancer. Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:(Abstract 3658).
  • ANDERSON N, LOKICH J, KALMAN L et al.: Preliminary Data on Weekly Irinotecan (CPT) with Continuous Capecitabine (X) in Metastatic Colorectal Cancer (MCRC) Patients (pts).J Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:(Abstract 3755).
  • BORNER MM, DIETRICH D, POPESCU R et al: A Randomized Phase II Trial of Capecitabine (CAP) and Two Different Schedules of Irinotecan (IRI) in First-line Treatment of Metastatic Colorectal Cancer (MCC). Proc. Am. Soc. Oncol (2003) 22:266 (Abstract 1068).
  • GOLD PJ, GODFREY T, DHAMI M et al: Capecitabine and Irinotecan as 1st Line Therapy for Patients With Metastatic Colorectal Cancer: Phase II Study Preliminary Results. Proc. Am. Soc. Clin. Oncol (2003) 22:288 (Abstract 1158).
  • KIM TW, KANG WK, PARK JO et al: Phase II Study of Irinotecan Plus Capecitabine as First Line Chemotherapy in Advanced Colorectal Cancer. Proc. Am. Soc. Oncol (2003) 22:318 (Abstract 1278).
  • GROTHEY A, JORDAN K, KELLNER 0 et al.: Randomized Phase II trial of capecitabine plus irinotecan (CapIri) versus capecitabine plus oxaliplatin (Cap0x) as first-line therapy of advanced colorectal cancer (ACRC). Proc. Am. Soc. Clin. Oncol (2003) 22:255 (Abstract 1022).
  • COPUR MS, LEDAKIS P, BOLTON M et al.: Capecitabine and Irinotecan on a Two-week On One-week Off Schedule for Previously Treated Metastatic Colorectal Cancer. Proc. Am. Soc. Clin. Oncol (2003) 22:302 (Abstract 1212).
  • BARRIOS CH, VIOLA F, CAMILLO-COURA L, SILVA RF, DEL GIGLIO A, MATHIAS C: Phase II Study of Capecitabine and Irinotecan as First Line Treatment in Metastatic Colorectal Cancer: First Trial of the Brazilian Oncology Consortium (BOC-CRC 001). J. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22(Abstract 3725).
  • WILLER AM, HOFHEINZ RD, WEIN A et al.: A Phase II trial of second line irinotecan and capecitabine after failure of first line infusional 5-fluorouracil and folinic acid in metastatic colorectal cancer (MCRC). I Clin. Oncol. 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:(Abstract 3752).
  • GROTHEY A, JORDAN K, KELLNER 0 et al.: Capecitabine/irinotecan (CapIri) and capecitabine/oxaliplatin (Cap0x) are active second-line protocols in patients with advanced colorectal cancer (ACRC) after failure of first-line combination therapy: results of a randomized Phase II study. J. Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:(Abstract 3534).
  • SCHEITHAUER W, KORNEK GV, RADERER M et al.: Randomized multicenter Phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer..1 Clin. Oncol (2003) 21:1307–1312.
  • ZEULI M, NARDONI C, PINO MS et al: Phase II study of capecitabine and oxaliplatin as first-line treatment in advanced colorectal cancer. Ann. Oncol (2003) 14:1378–1382.
  • SHIELDS AF, ZALUPSKI MM, MARSHALL JL, MEROPOL NJ: Treatment of advanced colorectal carcinoma with oxaliplatin and capecitabine: a Phase II trial. Cancer (2004) 100:531–537.
  • CASSIDY J, TABERNERO J, TWELVES C et al.: XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. Clin. Oncol (2004) 22:2084–2091.
  • MAKATSORIS T, PAPADIMITRIOU C, KARINA M et al.: A Phase II study of capecitabine and oxaliplatin as first line treatment for advanced colorectal carcinoma (CRC). A Hellenic Cooperative Oncology Group (HeCOG) study. Proc. Am. Soc. Clin. Oncol (2003) 22:360 (Abstract 1447).
  • BORNER MM, DIETRICH D, STUPP R et al.: Phase II study of capecitabine and oxaliplatin in first- and second-line treatment of advanced or metastatic colorectal cancer. J. Clin. Oncol. (2002) 20:1759–1766.
  • PFEIFFER P, GLIMELIUS B, SORBYE H et al.: Phase II study of short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) in patients with progressive colorectal cancer after irinotecan and 5-fluorouracil (FU) treatment. I Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3562.
  • LOPEZ-VIVANCO G, MUNOZ A, MANE JM et al.: Combination of oxaliplatin and capecitabine (CAPDX) in first and second-line treatment for metastatic colorectal carcinoma (MCRC). j Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3701.
  • ARKENAU HT, SCHMOLL H, KUBICKA S et al.: Phase III trial of infusional 5-fluorouracil/folinic acid plus oxaliplatin (FUFOX) versus capecitabine plus oxaliplatin (CAPDX) as first line treatment in advanced colorectal carcinoma (ACRC): Results of an interim safety analysis. I Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3546.
  • ANDRE T, LOUVET C, MAINDRAULT-GOEBEL F et al.: CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur. J. Cancer (1999) 35:1343–1347.
  • MAINDRAULT-GOEBEL F, LOUVET C, ANDRE T et al: Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6). GERCOR. Eur. I Cancer (1999) 35:1338–1342.
  • TOURNIGAND C, ANDRE T, ACHILLE E et al.: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. I Clin. Oncol (2004) 22:229–237.
  • ••A Phase III trial demonstrating mediansurvival of 20 months when patients receive infusional 5-FU and either irinotecan or oxaliplatin followed by the alternative infusional regime on disease progression.
  • SOUGLAKOS J, MAVROUDIS D, KAKOLYRIS S et al.: Triplet combination with irinotecan plus oxaliplatin plus continuous-infusion fluorouracil and leucovorin as first-line treatment in metastatic colorectal cancer: a multicenter Phase II trial. I Clin. Oncol (2002) 20:2651–2657.
  • CALVO E, CORTES J, RODRIGUEZ J et al.: Irinotecan, oxaliplatin, and 5-fluorouracil/leucovorin combination chemotherapy in advanced colorectal carcinoma: a Phase II study. Clin. Colorectal Cancer (2002) 2:104–110.
  • MASI G, ALLEGRINI G, CUPINI S et al: First-line treatment of metastatic colorectal cancer with irinotecan, oxaliplatin and 5-fluorouracil/leucovorin (FOLFOXIRI): results of a Phase II study with a simplified biweekly schedule. Ann. Oncol (2004) 15:1766–1772.
  • REINA JJ, SANCHEZ-ROVIRA P, BERNABE R et al.: Biweekly administration of irinotecan (CPT-11), oxaliplatin (OX) and 5-fluorouracil (5-FU) as first-line treatment of advanced or metastatic colorectal cancer (MCRC). Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3561.
  • SOUGLAKOS J, ZIRAS N, POLYZOS A et al: Oxaliplatin (L-OHP) combined with irinotecan (CPT-11), leucovorin (LV) and fluorouracil (5-FU) compared with irinotecan, leucovorin and fluorouracil as first-line treatment for metastatic colorectal cancer (MCC): preliminary results of a multicenter randomized Phase III trial. Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:(Abstract 3532).
  • MAUGHAN T: Fluorouracil (FU), oxaliplatin (OX), CPT-11 (irinotecan, Ir), use and sequencing, in advanced colorectal cancer (ACRC): The UK MRC FOCUS (CR08) Trial. Proc. Am. Soc. Clin. Oncol CI Symposium (2005) (Abstract 165).
  • GROTHEY A, SARGENT D, GOLDBERG RM, SCHMOLL HJ: Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. I Clin. Oncol (2004) 22:1209–1214.
  • ••An analysis of seven published Phase IIItrials showing that survival improved with the availability of 5-FLAV, irinotecan and oxaliplatin at some point during the course of treatment for CRC.
  • BOLLAG DM, MCQUENEY PA, ZHU J et al: Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res. (1995) 55:2325–33.
  • KOWALSKI RJ, GIANNAKAKOU P, HAMEL E: Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxo13). I Biol. Chem. (1997) 272:2534–2541.
  • GIANNAKAKOU P, SACKETT DL, KANG YK et al.: Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization. J. Biol. Chem. (1997) 272:17118–17125.
  • POPLIN E, MOORE M, O'DWYER P et al.: Safety and efficacy of EP0906 in patients with advanced colorectal cancer: a review of 2 Phase II trials. Proc. Am. Soc. Clin. Oncol (2003) 22:283 (Abstract 1135).
  • LEE FY, BORZILLERI R, FAIRCHILD CR et al: BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin. Cancer Res. (2001) 7:1429–1437.
  • ENG C, KINDLER HL, NATTAM S et al.: A Phase II trial of the epothilone B analog, BMS-247550, in patients with previously treated advanced colorectal cancer. Ann. Oncol (2004) 15:928–932.
  • MacDONALD JR, MUSCOPLAT CC, DEXTER DL et al.: Preclinical antitumor activity of 6-hydroxymethylacylfulvene, a semisynthetic derivative of the mushroom toxin illudin S. Cancer Res. (1997) 57:279–283.
  • NASTA SD, HOFF PM, GEORGE CS et al.: Phase II study of MGI-114 administered intravenously for 5 days every 28 days to patients with metastatic colorectal cancer. Am. J. Clin. Oncol. (2003) 26:132–134.
  • BRITTEN CD, HILSENBECK SG, ECKHARDT SG et al.: Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model. Cancer Res. (1999) 59:1049–1053.
  • VALLEJOS C, VARELA M, ROCA E et al.: Phase II trial of irofulven (IROF) and CPT-11 in metastatic colorectal cancer (MCRC) patients (pts) failing oxaliplatin (OXA)/5FU based chemotherapy. I Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22 (Abstract 3713).
  • VEIKKOLA T, KARKKAINEN M, CLAESSON-WELSH L, ALITALO K: Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res. (2000) 60:203–212.
  • PRESTA LG, CHEN H, O'CONNOR SJ et al.: Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. (1997) 57:4593–4599.
  • KABBINAVAR F, HURWITZ HI, FEHRENBACHER L et al: Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. ./. Clin. Oncol (2003) 21:60–65.
  • GIANTONI BJ, LEVY D, O'DWYER PJ, MEROPOL NJ, CATALANO PJ, BENSON AB: Bevacizumab (anti-VEGF) plus IFL (irinotecan, fluorouracil, leucovorin) as front-line therapy for advanced colorectal cancer (advCRC): Results from the Eastern Cooperative Oncology Group (ECOG) Study E2200. Proc. Am. Soc. Clin. Oncol. (2003) 22:255 (Abstract 1024).
  • HURWITZ H, FEHRENBACHER L, NOVOTNY W et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl..). Med. (2004) 350:2335–2342.
  • ••A large Phase III trial showing improvedmedian survival (>20 months) when bevacizumab is added to bolus irinotecan/ 5-FU/LV.
  • FYFE GA, HURWITZ H, FEHRENBACHER L et al: Bevacizumab plus irinotecan/5-FU/leucovorin for treatment of metastatic colorectal cancer results in survival benefit in all pm-specified patient subgroups. I Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3617 (Abstract).
  • HURWITZ H, FEHRENBACHER L, CART WRIGHT T et al.: Wound healing/ bleeding in metastatic colorectal cancer patients who undergo surgery during treatment with bevacizumab. 1 Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3702 (Abstract).
  • SCAPPATICCI F, FEHRENBACHER L, CARTWRIGHT T et al.: Lack of effect of bevacizumab on wound healing/bleeding complications when given 28–60 days following primary cancer surgery. J. Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:(Abstract 3530).
  • KABBINAVAR FE SCHULZ J, McCLEOD M et al.: Addition of Bevacizumab to Bolus Fluorouracil and Leucovorin in First-Line Metastatic Colorectal Cancer: Results of a Randomized Phase II Trial. J. Clin. Oncol (2005)
  • MASS RD, FYFE G, HAMBLETON J et al.: Bevacizumab in combination with 5-FU/leucovorin improves survival in patients with metastatic colorectal cancer: A combined analysis. I Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:(Abstract 3616).
  • GIANTONIO BJ, CATALANO PJ, MEROPOL NJ et al: High-dose bevacizumab in combination with FOLFOX4 improves survival in patients with previously treated advanced colorectal cancer: Results from the Eastern Cooperative Oncology Group# (ECOG) study E3200. Proc. Am. Soc. Clin. Oncol GI Symposium (2005) (Abstract 169a).
  • •A promising initial report of improved outcomes with the addition of bevacizumab to ozaliplatin/5-FU/LV.
  • HOCHSTER HS, WELLES L, HART L et al.: Bevacizumab (B) with oxaliplatin (0)-based chemotherapy in the first-line therapy of metastatic colorectal cancer (mCRC): preliminary results of the randomized 'TREE-2' trial. Proc. Am. Soc. Oncol CI Symposium (2005) (Abstract 241).
  • •A promising initial report on the addition of bevacizumab to oxaliplatin/ fluoropyrimidine combinations.
  • WOOD JM, BOLD G, BUCHDUNGER E et al: PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. (2000) 60:2178–2189.
  • SCHLEUCHER N, TRARBACH T, JUNKER U et al: Phase I/II study of PTK787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor in combination with FOLFIRI as first-line treatment for patients with metastatic colorectal cancer. Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3558 (Abstract).
  • STEWAR WP, THOMAS A, MORGAN B et al.: Expanded Phase I/II study of PTK787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in combination with FOLFOX-4 as first-line treatment for patients with metastatic colorectal cancer. Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3556 (Abstract).
  • PAN Q, KLEER CG, VAN GOLEN KL et al.: Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis. Cancer Res. (2002) 62:4854–4859.
  • PAN Q, BAO LW, MERAJVER SD: Tetrathiomolybdate inhibits angiogenesis and metastasis through suppression of the NFkappaB signaling cascade. Mol. Cancer Res. (2003) 1:701–706.
  • MIYANAGA K, KATO Y, NAKAMURA T et al.: Expression and role of thrombospondin-1 in colorectal cancer. Anti-Cancer Res. (2002) 22:3941–3948.
  • TOMII Y, KAMOCHI J, YAMAZAKI H et al.: Human thrombospondin 2 inhibits proliferation of microvascular endothelial cells. Int. J. Oncol (2002) 20:339–342.
  • MAEDA K, NISHIGUCHI Y, YASHIRO M et al: Expression of vascular endothelial growth factor and thrombospondin-1 in colorectal carcinoma. Int/. Mol. Med. (2000) 5:373–8.
  • TOKUNAGA T, NAKAMURA M, OSHIKA Y et al.: Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer. Br. J. Cancer (1999) 79:354–359.
  • ALLEGRINI G, GOULETTE FA, DARNOWSKI JW, CALABRESI P: Thrombospondin-1 plus irinotecan: a novel antiangiogenic-chemotherapeutic combination that inhibits the growth of advanced human colon tumor xenografts in mice. Cancer Chemother. Pharmacol (2004) 53:261–266.
  • POSEY JA, NG TC, YANG B et al: A Phase I study of anti-kinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma. Clin. Cancer Res. (2003) 9:1323–1332.
  • UN P, SANKAR S, SHAN S et al: Inhibition of tumor growth by targeting tumor endothelium using a soluble vascular endothelial growth factor receptor. Cell Growth Differ. (1998) 9:49–58.
  • HOLASH J, DAVIS S, PAPADOPOULOS N et al: VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc. Nati Acad. Sci. USA (2002) 99:11393–11398.
  • DRIXLER TA, RINKES IH, RITCHIE ED, VAN VROONHOVEN TJ, GEBBINK ME VOEST EE: Continuous administration of angiostatin inhibits accelerated growth of colorectal liver metastases after partial hepatectomy. Cancer Res. (2000) 60:1761–1765.
  • TE VELDE EA, VOGTEN JM, GEBBINK ME VAN GORP JM, VOEST EE, BOREL RINKES IH: Enhanced antitumour efficacy by combining conventional chemotherapy with angiostatin or endostatin in a liver metastasis model. Br. J. Surg. (2002) 89:1302–1309.
  • PAVCO PA, BOUHANA KS, GALLEGOS AM et al: Antitumor and antimetastatic activity of ribozymes targeting the messenger RNA of vascular endothelial growth factor receptors. Clin. Cancer Res. (2000) 6:2094–2103.
  • WENG DE, USMAN N: Angiozyme: a novel angiogenesis inhibitor. Curl: Oncol Rep. (2001) 3:141–146.
  • STOELTZING 0, LIU W, REINMUTH N et al.: Inhibition of integrin alpha5betal function with a small peptide (ATN-161) plus continuous 5-FU infusion reduces colorectal liver metastases and improves survival in mice. Int. J. Cancer. (2003) 104:496–503.
  • GOVINDARAJAN R, SAFAR AM, MADDOX A-M, HUTCHINS LF: Irinotecan and thalidomide prolong disease free and overall survival in 5FU refractory metastatic colorectal cancer. Proc. Am. Soc. Oncol (2003) 22:249 (Abstract 997).
  • FAIRBROTHER WJ, CHRISTINGER HW, COCHRAN AG et al.: Novel peptides selected to bind vascular endothelial growth factor target the receptor-binding site. Biochemistry (1998) 37:17754–64.
  • BARNES CJ, KUMAR R: Biology of the epidermal growth factor receptor family. Cancer Treat. Res. (2004) 119:1–13.
  • GOLDSTEIN NI, PREWETT M, ZUKLYS K, ROCKWELL P, MENDELSOHN J: Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin. Cancer Res. (1995) 1:1311–1318.
  • PREWETT MC, HOOPER AT, BASSI R, ELLIS LM, WAKSAL HW, HICKLIN DJ: Enhanced antitumor activity of anti-epidermal growth factor receptor monoclonal antibody IMC-C225 in combination with irinotecan (CPT-11) against human colorectal tumor xenografts. Chi'. Cancer Res. (2002) 8:994–1003.
  • SALTZ LB, MEROPOL NJ, LOEHRER PJ, NEEDLE MN, KOPIT J, MAYER RJ: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. ./. Clin. Oncol. (2004) 22:1201–1208.
  • LENZ HJ, MAYER RJ, GOLD PJ et al: Activity of cetuximab in patients with colorectal cancer refractory to both irinotecan and oxaliplatin. 1 Clin. Oncol, 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004)22:Abstract 3510.
  • SALTZ L, RUBIN M, HOCHSTER H et al: Cetuximab (IMC-C225) Plus Irinotecan (CPT-11) is Active in CPT-11-Refractory Colorectal Cancer (CRC) that Expresses Epidermal Growth Factor Receptor (EGER). Proc. Am. Soc. Clin. Oncol (2001) 20:(Abstract 7).
  • CUNNINGHAM D, HUMBLET Y, SIENA S et al.: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl. I Med. (2004) 351:337–345.
  • ••A randomised trial showing activity ofcetuximab, alone or with irinotecan, in patients with irinotecan-refractory colorectal cancer
  • CHUNG KY, SHIA J, KEMENY NE et al.: Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. j Clin. Oncol. (2005) 23:1803–1810.
  • ••An analysis reporting responses tocetuximab in patients with EGER-negative CRCs, indicating that EGER expression by IHC was not predictive of response to cetuximab
  • ROSENBERG AH, LOEHRER PJ, NEEDLE MN et al: Erbitux (IMC-C225) plus weekly irinotecan (CPT-11), fluorouracil (5FU) and leucovorin (LV) in colorectal cancer (CRC) that expresses the epidermal growth factor receptor (EGFr). Proc. Am. Soc. Clin. Oncol. (2002) 21:(Abstract 536).
  • FOLPRECHT G, LUTZ MP, SCHOEFFSKI P et al: Pharmacokinetic (PK) evaluation of cetuximab in combination with weekly irinotecan (CPT-11) and 24-h infusional 5-FU/folinic acid (FA) as first line treatment in patients (pts) with epidermal growth factor receptor (EGFR)-positive metastatic colorectal cancer (MCRC). Proc. Am. Soc. Clin. Oncol. (2003) 22:222 (Abstract 890).
  • ROUGIER P, RAOUL J-L, VAN LAETHEM J-L et al.: Cetuximab + FOLFIRI as first-line treatment for metastatic colorectal CA. I Clinical Oncology 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22: (Abstract 3513).
  • TABERNERO JM, VAN CUTSEM E, SASTRE J et al.: An international Phase II study of cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with metastatic colorectal cancer (CRC) expressing Epidermal Growth Factor Receptor (EGFR). Preliminary results. I Clin. Oncol, 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22: (Abstract 3512).
  • BADARINATH S, MITCHELL EP, JENNIS A et al: Cetuximab plus FOLFOX for colorectal cancer (EXPLORE): Preliminary safety analysis of a randomized Phase III trial. I Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3531 (Abstract).
  • SALTZ LB, LENZ H, KINDLER H et al: Interim report of randomized Phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer. Proc. Am. Soc. OM Oncol CI Symposium (2005) (Abstract 169b).
  • ••A promising initial report of thecombination of bevacizumab and cetuximab
  • KETTLEBOROUGH CA, SALDANHA J, HEATH VJ, MORRISON CJ, BENDIG MM: Humanization of a mouse monoclonal antibody by CDR-grafting: the importance of framework residues on loop conformation. Protein Eng. (1991) 4:773–783.
  • VANHOEFER U, TEWES M, ROJO F et al.: Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor.Oncol (2004) 22:175–184.
  • YANG XD, JIA XC, CORVALAN JR, WANG P, DAVIS CG: Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Grit. Rev Oncol Hematol (2001) 38:17–23.
  • HECHT JR, PATNAIK A, MALIK I et al.: ABX-EGF monotherapy in patients (pts) with metastatic colorectal cancer (mCRC): An updated analysis. I Clin. Oncol. 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3511 (Abstract).
  • WAKELING AE, GUY SP, WOODBURN JR et al.: ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res. (2002) 62:5749–5754.
  • CIARDIELLO F, CAPUTO R, BIANCO R et al: Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin. Cancer Res. (2000) 6:2053–2063.
  • STEWART CF, LEGGAS M, SCHUETZ JD et al: Gefitinib enhances the antitumor activity and oral bioavailability of irinotecan in mice. Cancer Res. (2004) 64:7491–7499.
  • KOIZUMI F, KANZAWA F, UEDA Y et al.: Synergistic interaction between the EGFR tyrosine kinase inhibitor gefitinib ('Iressi) and the DNA topoisomerase I inhibitor CPT-11 (irinotecan) in human colorectal cancer cells. Int. I Cancer. (2004) 108:464–472.
  • CHAU I, MASSEY A, HIGGINS L, BOTWOOD N, CUNNINGHAM D: Phase I study of gefitinib in combination with irinotecan in patients with fluoropyrimidine refractory advanced colorectal cancer (CRC). ./. Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3572 (Abstract).
  • REDLINGER M, KRAMER A, FLAHERTY K, SUN W, HALLER D, O'DWYER PJ: A Phase II trial of gefitinib in combination with 5-FU/LV/irinotecan in patients with colorectal cancer." Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3767 (Abstract).
  • FISHER GA, KUO T, CHO CD et al: A Phase II study of gefitinib in combination with FOLFOX-4 (IFOX) in patients with metastatic colorectal cancer. .1 Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3514 (Abstract).
  • MOYER JD, BARBACCI EG, IWATA KK et al: Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. (1997) 57:4838–4848.
  • HIDALGO M, SIU LL, NEMUNAITIS J et al.: Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. I Clin. Oncol. (2001) 19:3267–3279.
  • OZA AM, TOWNSLEY CA, SIU LL et al: Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer. Proc. Am. Soc. Clin. Oncol (2003) 22:196 (Abstract 785).
  • MEYERHARDT JA, XHU A, ENZINGER PC et al.: Phase II study of capecitabine, oxaliplatin and erlotinib in previously treated patients with metastatic colorectal cancer (MCRC). I Clin. Oncol. 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3580 (Abstract).
  • MESSERSMITH WA, LAHERU DA, SENZER NN et al.: Phase I trial of irinotecan, infusional 5-fluorouracil, and leucovorin (FOLFIRI) with erlotinib (OSI-774): early termination due to increased toxicities. Clin. Cancer Res. (2004) 10:6522–6527.
  • XIA W, MULLIN RJ, KEITH BR et al: Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/ErbB2 and downstream Erk1/2 and AKT pathways. Oncogene (2002) 21:6255–6263.
  • WISSNER A, OVERBEEK E, REICH MF et al.: Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (HER-2). I Med. Chem. (2003) 46:49–63.
  • CALVO E, TOLCHER AW, HAMMOND LA et al.: Administration of CI-1033, an irreversible pan-ErbB tyrosine kinase inhibitor, is feasible on a 7-day on, 7-day off schedule: a Phase I pharmacokinetic and food effect study. Clin. Cancer Res. (2004) 10:7112–7120.
  • ANDREYEV HJ, NORMAN AR, CUNNINGHAM D, OATES JR, CLARKE PA: Kirsten ras mutations in patients with colorectal cancer: the multicenter 'RASCAL' study. I Nati Cancer Inst. (1998) 90:675–684.
  • ANDREYEV HJ, NORMAN AR, CUNNINGHAM D et al.: Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br. J. Cancer. (2001) 85:692–696.
  • LIU M, BRYANT MS, CHEN J et al: Antitumor activity of SCH-66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res. (1998) 58:4947–4956.
  • WANG E, CASCIANO CN, CLEMENT RP, JOHNSON WW: The farnesyl protein transferase inhibitor 5CH66336 is a potent inhibitor of MDR1 product P-glycoprotein. Cancer Res. (2001) 61:7525–7529.
  • SHARMA S, KEMENY N, KELSEN DP et al.: A Phase II trial of farnesyl protein transferase inhibitor SCH-66336, given by twice-daily oral administration, in patients with metastatic colorectal cancer refractory to 5-fluorouracil and irinotecan. Ann. Oncol. (2002) 13:1067-1071. zoo. END DW, SMETS G, TODD AV et al.: Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. (2001) 61:131–137.
  • RAO S, CUNNINGHAM D, DE GRAMONT A et al: Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer. Clin. Oncol. (2004) 22:3950–3957.
  • WELLER SG, KLEIN IK, PENINGTON RC, KARNES WE Jr: Distinct protein kinase C isozymes signal mitogenesis and apoptosis in human colon cancer cells. Gastroenterology (1999) 117:848–57.
  • ZONDER JA, SHIELDS AF, ZALUPSK M et al: A Phase II trial of bryostatin 1 in the treatment of metastatic colorectal cancer. Clip. Cancer Res. (2001) 7:38–42.
  • KAUR G, STETLER-STEVENSON M, SEBERS S et al.: Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275.1 Natl. Cancer Inst. (1992) 84:1736–1740.
  • BIBLE KC, KAUFMANN SH: Flavopiridol: a cytotoxic flavone that induces cell death in noncycling A549 human lung carcinoma cells. Cancer Res. (1996) 56:4856–4861.
  • BRUSSELBACH S, NETTELBECK DM, SEDLACEK HH, MULLER R: Cell cycle-independent induction of apoptosis by the anti-tumor drug Flavopiridol in endothelial cells. Int. I Cancer (1998) 77:146–152.
  • BIBLE KC, KAUFMANN SH: Cytotoxic synergy between flavopiridol (NSC 649890, L86-8275) and various antineoplastic agents: the importance of sequence of administration. Cancer Res. (1997) 57:3375–3380.
  • MOTWANI M, JUNG C, SIROTNAK FM et al: Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts. Clia Cancer Res. (2001) 7:4209–4219.
  • MOTWANI MV, RACANELLI A, SCHWARTZ GK: Flavopiridol potentiates effect of oxaliplatin in vitro and in vivo and requires intact p53. I Clia Oncol. 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3145 (Abstract).
  • JUNG C, MOTWANI M, KORTMANSKY J et al.: The cyclin-dependent kinase inhibitor flavopiridol potentiates gamma-irradiation-induced apoptosis in colon and gastric cancer cells. Clip. Cancer Res. (2003) 9:6052–6061.
  • AKLILU M, KINDLER HL, DONEHOWER RC, MANI S, VOKES EE: Phase II study of flavopiridol in patients with advanced colorectal cancer. Ann. Oncol. (2003) 14:1270–1273.
  • AKINAGA S, GOMI K, MORIMOTO M, TAMAOKI T, OKABE M: Antitumor activity of UCN-01, a selective inhibitor of protein kinase C, in murine and human tumor models. Cancer Res. (1991) 51:4888–4892.
  • KAWAKAMI K, FUTAMI H, TAKAHARA J, YAMAGUCHI K: UCN-01, 7-hydroxyl-staurosporine, inhibits kinase activity of cyclin-dependent kinases and reduces the phosphorylation of the retinoblastoma susceptibility gene product in A549 human lung cancer cell line. Biochem. Biophys. Res. Commun. (1996) 219:778–783.
  • SEBOLT-LEOP OLDJS, DUDLEY DT, HERRERA R et al.: Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat. Med. (1999) 5:810–816.
  • RINEHART J, ADJEI AA, LORUSSO PM et al.: Multicenter Phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. Clia Oncol. (2004) 22:4456–4462.
  • WILHELM SM, CARTER C, TANG L et al: BAY-43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. (2004) 64:7099–7109.
  • PRIMROSE JN, BLEIBERG H, DANIEL F et al.: Marimastat in recurrent colorectal cancer: exploratory evaluation of biological activity by measurement of carcinoembryonic antigen. BE J. Cancer (1999) 79:509–514.
  • NORTH H, KING J, MORRIS DL: Effect of marimastat on serum tumour markers in patients with colorectal cancer. Int. Surg. Investig. (2000) 2:213–217.
  • KING J, ZHAO J, CLINGAN P, MORRIS D: Randomised double blind placebo control study of adjuvant treatment with the metalloproteinase inhibitor, Marimastat in patients with inoperable colorectal hepatic metastases: significant survival advantage in patients with musculoskeletal side-effects. Anti-Cancer Res. (2003) 23:639–645.
  • EBERHART CE, COFFEY RJ, RADHIKA A, GIARDIELLO FM, FERRENBACH S, DUBOIS RN: Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology (1994) 107:1183–1188.
  • KARGMAN SL, O'NEILL GP, VICKERS PJ, EVANS JF, MANCINI JA, JOTHY S: Expression of prostaglandin G/ H synthase-1 and -2 protein in human colon cancer. Cancer Res. (1995) 55:2556–2559.
  • SANO H, KAWAHITO Y, WILDER RL et al.: Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res. (1995) 55:3785–3789.
  • GIARDIELLO FM, HAMILTON SR, KRUSH AJ et al: Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl. I Med. (1993) 328:1313–1316.
  • STEINBACH G, LYNCH PM, PHILLIPS RK et al: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl. Med. (2000) 342:1946-1952.627
  • THUN MJ, NAMBOODIRI MM, HEATH CW, JR.: Aspirin use and reduced risk of fatal colon cancer. N Engl. J. Med. (1991) 325:1593–1596.
  • SHEEHAN KM, SHEAHAN K, O'DONOGHUE DP et al: The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA (1999) 282:1254–1257.
  • BLANKE CD, BENSON III AB, DRAGOVICH T et al: A Phase II trial of celecoxib (CX), irinotecan (I), 5-Fluorouracil (5FU), and leucovorin (LCV) in patients (pts) with unresectable or metastatic colorectal cancer (CRC). Proc. Am. Soc. Clin. Oncol (2002) 21:505 (Abstract).
  • PAN C, LOEHRER P, JULIAR B et al: A Phase II trial of irinotecan (I), 5-fluorouracil (F), leucovorin (L) (IFL), celecoxib and glutamine as first line therapy for advanced colorectal cancer (CRC): A Hoosier Oncology Group Study. Proc. Am. Soc. Clin. Oncol (2003) 22:335 (Abstract 1347).
  • UN EH, MORRIS J, CHAU NK et al: Celecoxib attenuated capecitabine induced hand-and-foot syndrome (HFS) and diarrhea and improved time to tumor progression in metastatic colorectal cancer (MCRC). Proc. Am. Soc. Clin. Oncol (2002) 21:2364 (Abstract).
  • EL-RAYES BF, SHIELDS AF, VAISHAMPAYAN UN et al: Phase II study of capecitabine, irinotecan, and celecoxib in advanced colorectal cancer. Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3766 (Abstract).
  • AGAFITEI RD, SCHNEIDER S, IQBAL S, YANG D, GROSHEN S, LENZ HJ: Effect of celecoxib on neurotoxicity in patients with metastatic colorectal cancer treated with 5-FU/ oxaliplatin (CIFOX).j Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3600 (Abstract).
  • GASPARINI G, GATTUSO D, MORABITO A et al.: Rofecoxib associated with weekly irinotecan and infusional 5-fluorouracil as second-line treatment for metastatic colorectal cancer. ./. Clin. Oncol 2004 ASCO Annual Meeting Proceedings (Post Meeting Edition) (2004) 22:3686.
  • BECERRA CR, FRENKEL EP, ASHFAQ R, GAYNOR RB: Increased toxicity and lack of efficacy of Rofecoxib in combination with chemotherapy for treatment of metastatic colorectal cancer: A Phase II study. Int. J. Cancer (2003) 105:868–872.
  • BOMBARDIER C, LAINE L, REICIN A et al: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl. I Med. (2000) 343:1520–1528.
  • JUNI P, NARTEY L, REICHENBACH S, STERCHI R, DIEPPE PA, EGGER M: Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet. (2004) 364:2021–2029.
  • FITZGERALD GA: Coxibs and cardiovascular disease. N Engl. I Med. (2004) 351:1709–1711.
  • SOLOMON SD, McMURRAY JJ, PFEFFER MA et al.: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl. J. Med. (2005) 352:1071–80.
  • NAITO Y, SAITO K, SHIIBA K et al: CD8' T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. (1998) 58:3491–3494.
  • NAGORSEN D, KEILHOLZ U, RIVOLTINI L et al: Natural T-cell response against MHC class I epitopes of epithelial cell adhesion molecule, her-2/neu, and carcinoembryonic antigen in patients with colorectal cancer. Cancer Res. (2000) 60:4850–4854.
  • MOSOLITS S, STEINITZ M, HARMENBERG U et al.: Immunogenic regions of the GA733-2 tumour-associated antigen recognised by autoantibodies of patients with colorectal carcinoma. Cancer Immunol Immunother. (2002) 51:209–218.
  • CRIPPS MC, FIGUEREDO AT, OZA AM et al: Phase II randomized study of ISIS 3521 and ISIS 5132 in patients with locally advanced or metastatic colorectal cancer: a National Cancer Institute of Canada clinical trials group study. OM. Cancer Res. (2002) 8:2188–92.
  • MARSHALL JL, EISENBERG SG, JOHNSON MD et al: A Phase II trial of ISIS 3521 in patients with metastatic colorectal cancer. Clin. Colorectal Cancer. (2004) 4:268–274.
  • SALEH M, POSEY J, PLEASANT L et al: A Phase II Trial of ISIS 2503, an Antisense Inhibitor of H-ras, as First Line Therapy for Advanced Colorectal Carcinoma. Proc. Am. Soc. Clin. Oncol (2000) 19:1258 (Abstract).
  • OCHOA L, KUHN J, SALINAS R et al: A Phase I, Pharmacokinetic, and Biologic Correlative Study of G3139 and Irinotecan (CPT-11) in Patients with Metastatic Colorectal Cancer. Proc. Am. Soc. Clin. Oncol (2001) 20:297 (Abstract).
  • ADAMS J, PALOMBELLA VJ, SAUSVILLE EA et al: Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. (1999) 59:2615–22.
  • TEICHER BA, ARA G, HERBST R, PALOMBELLA VJ, ADAMS J: The proteasome inhibitor PS-341 in cancer therapy. Clin. Cancer Res. (1999) 5:2638–45.
  • CUSACK JC, JR., LIU R, HOUSTON M et al.: Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor KB inhibition. Cancer Res. (2001) 61:3535–3540.
  • KRAKER AJ, MIZZEN CA, HARTL BG, MIIN J, ALLIS CD, MERRIMAN RU: Modulation of histone acetylation by (4-lacetylaminol - (2-amino-phenyl) benzamide) in HCT-8 colon carcinoma. Mol Cancer Ther. (2003) 2:401–408.
  • SCHRAG D: The price tag on progress-chemotherapy for colorectal cancer. N Engl. J. Med. (2004) 351:317–9.
  • •An important discussion about the cost Issues related to recent advances in the management of patients with CRC.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.