331
Views
28
CrossRef citations to date
0
Altmetric
Drug Safety Evaluations

Targeting thymidylate synthase in colorectal cancer: critical re-evaluation and emerging therapeutic role of raltitrexed

, , , &

Bibliography

  • Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 2010;46(4):765-81
  • Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61(2):69-90
  • Meta-alalysis Group in Cancer. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. Meta-analysis Group In Cancer. J Clin Oncol 1998;16(1):301-8
  • Wolmark N, Rockette H, Mamounas E, et al. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol 1999;17(11):3553-9
  • Sobrero AF, Aschele C, Bertino JR. Fluorouracil in colorectal cancer–a tale of two drugs: implications for biochemical modulation. J Clin Oncol 1997;15(1):368-81
  • Kopetz S, Chang GJ, Overman MJ, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol 2009;27(22):3677-83
  • Andre T, Boni C, Navarro M, et al. 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(19):3109-16
  • Yothers G, O'Connell MJ, Allegra CJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol 2011;29(28):3768-74
  • 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. J Clin Oncol 2004;22(1):23-30
  • Jackman AL, Boyle FT, Harrap KR. Tomudex (ZD1694): from concept to care, a programme in rational drug discovery. Invest New Drugs 1996;14(3):305-16
  • Cunningham D, Zalcberg J, Maroun J, et al. Efficacy, tolerability and management of raltitrexed (Tomudex) monotherapy in patients with advanced colorectal cancer. a review of phase II/III trials. Eur J Cancer 2002;38(4):478-86
  • 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(9317):1555-63
  • Popov I, Carrato A, Sobrero A, et al. Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1). Eur J Cancer 2008;44(15):2204-11
  • Price T, Wilson K, Simes RJ, et al. Final results of Australasian Gastro-Intestinal Trials Group (AGITG) ARCTIC Study. An international audit of raltitrexed for patients with cardiac toxicity induced by fluoropyrimidines (FP). Paper presented at Annals Oncology, ESMO; Vienna, Austria; 2012
  • Kelly C, Bhuva N, Harrison M, et al. Use of raltitrexed as an alternative to 5-fluorouracil and capecitabine in cancer patients with cardiac history. Eur J Cancer 2013;49(10):2303-10
  • Edler D, Glimelius B, Hallstrom M, et al. Thymidylate synthase expression in colorectal cancer: a prognostic and predictive marker of benefit from adjuvant fluorouracil-based chemotherapy. J Clin Oncol 2002;20(7):1721-8
  • Popat S, Matakidou A, Houlston RS. Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J Clin Oncol 2004;22(3):529-36
  • Rahman L, Voeller D, Rahman M, et al. Thymidylate synthase as an oncogene: a novel role for an essential DNA synthesis enzyme. Cancer Cell 2004;5(4):341-51
  • Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003;3(5):330-8
  • Sotos GA, Grogan L, Allegra CJ. Preclinical and clinical aspects of biomodulation of 5-fluorouracil. Cancer Treat Rev 1994;20(1):11-49
  • Rustum YM, Harstrick A, Cao S, et al. Thymidylate synthase inhibitors in cancer therapy: direct and indirect inhibitors. J Clin Oncol 1997;15(1):389-400
  • Hospira UK Ltd. Tomudex summary of product characteristics. 2011
  • Clarke SJ, Hanwell J, de Boer M, et al. Phase I trial of ZD1694, a new folate-based thymidylate synthase inhibitor, in patients with solid tumors. J Clin Oncol 1996;14(5):1495-503
  • Grem JL, Sorensen JM, Cullen E, et al. A Phase I study of raltitrexed, an antifolate thymidylate synthase inhibitor, in adult patients with advanced solid tumors. Clin Cancer Res 1999;5(9):2381-91
  • 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(1):71-6
  • Clarke SJ, Beale PJ, Rivory LP. Clinical and preclinical pharmacokinetics of raltitrexed. Clin Pharmacokinet 2000;39(6):429-43
  • Judson I, Maughan T, Beale P, et al. Effects of impaired renal function on the pharmacokinetics of raltitrexed (Tomudex ZD1694). Br J Cancer 1998;78(9):1188-93
  • Judson IR. 'Tomudex' (raltitrexed) development: preclinical, phase I and II studies. Anticancer Drugs 1997;8(Suppl 2):S5-9
  • Zalcberg JR, Cunningham D, Van Cutsem E, et al. ZD1694: a novel thymidylate synthase inhibitor with substantial activity in the treatment of patients with advanced colorectal cancer. Tomudex Colorectal Study Group. J Clin Oncol 1996;14(3):716-21
  • 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(9):961-5
  • 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. J Clin Oncol 1998;16(9):2943-52
  • 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. Paper presented at ASCO Meeting Abstract; Denver, USA; 1997
  • Cunningham D. Mature results from three large controlled studies with raltitrexed ('Tomudex'). Br J Cancer 1998;77(Suppl 2):15-21
  • Editorial. Drug-company decision to end cancer trial. Lancet 1999;354(9184):1045
  • Wilson KS, Malfair Taylor SC. Raltitrexed: optimism and reality. Expert Opin Drug Metab Toxicol 2009;5(11):1447-54
  • Ducreux M, Bouche O, Pignon JP, et al. Randomised trial comparing three different schedules of infusional 5FU and raltitrexed alone as first-line therapy in metastatic colorectal cancer. Final results of the Federation Francophone de Cancerologie Digestive (FFCD) 9601 trial. Oncology 2006;70(3):222-30
  • Thomas RJ, Williams M, Garcia-Vargas J. Lessons learned from raltitrexed–quality assurance, patient education and intensive supportive drugs to optimise tolerability. Clin Oncol (R Coll Radiol) 2003;15(5):227-32
  • Raymond E, Chaney SG, Taamma A, et al. Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol 1998;9(10):1053-71
  • Comella P, Casaretti R, Sandomenico C, et al. Role of oxaliplatin in the treatment of colorectal cancer. Ther Clin Risk Manag 2009;5(1):229-38
  • Fizazi K, Ducreux M, Ruffie P, et al. Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer. J Clin Oncol 2000;18(11):2293-300
  • Scheithauer W, Kornek GV, Ulrich-Pur H, et al. Oxaliplatin plus raltitrexed in patients with advanced colorectal carcinoma: results of a Phase I-II trial. Cancer 2001;91(7):1264-71
  • Seitz JF, Bennouna J, Paillot B, et al. Multicenter non-randomized phase II study of raltitrexed (Tomudex) and oxaliplatin in non-pretreated metastatic colorectal cancer patients. Ann Oncol 2002;13(7):1072-9
  • Feliu J, Castanon C, Salud A, et al. Phase II randomised trial of raltitrexed-oxaliplatin vs raltitrexed-irinotecan as first-line treatment in advanced colorectal cancer. Br J Cancer 2005;93(11):1230-5
  • 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(5):716-20
  • Scheithauer W, Kornek GV, Schuell B, et al. Second-line treatment with oxaliplatin + raltitrexed in patients with advanced colorectal cancer failing fluoropyrimidine/leucovorin-based chemotherapy. Ann Oncol 2001;12(5):709-14
  • Gravalos C, Salut A, Garcia-Giron C, et al. A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line chemotherapy for advanced colorectal cancer. Clin Transl Oncol 2012;14(8):606-12
  • Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004;22(2):229-37
  • Colucci G, Gebbia V, Paoletti G, et al. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale. J Clin Oncol 2005;23(22):4866-75
  • Aschele C, Baldo C, Sobrero AF, et al. Schedule-dependent synergism between raltitrexed and irinotecan in human colon cancer cells in vitro. Clin Cancer Res 1998;4(5):1323-30
  • Ford HE, Cunningham D, Ross PJ, et al. Phase I study of irinotecan and raltitrexed in patients with advanced gastrointestinal tract adenocarcinoma. Br J Cancer 2000;83(2):146-52
  • Aparicio J, de las Penas R, Vicent JM, et al. Multicenter phase I study of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer. Oncology 2002;63(1):42-7
  • Stevenson JP, Redlinger M, Kluijtmans LA, et al. Phase I clinical and pharmacogenetic trial of irinotecan and raltitrexed administered every 21 days to patients with cancer. J Clin Oncol 2001;19(20):4081-7
  • Aparicio J, Vicent JM, Maestu I, et 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(7):1121-5
  • Feliu J, Salud A, Escudero P, et al. Irinotecan plus raltitrexed as first-line treatment in advanced colorectal cancer: a phase II study. Br J Cancer 2004;90(8):1502-7
  • Aparicio J, Vicent JM, Maestu I, et al. First-line treatment with irinotecan and raltitrexed in metastatic colorectal cancer. Mature results of a multicenter phase II study. Oncology 2005;68(1):58-63
  • Carnaghi C, Rimassa L, Garassino I, et al. Irinotecan and raltitrexed: an active combination in advanced colorectal cancer. Ann Oncol 2002;13(9):1424-9
  • Chiara S, Nobile MT, Tomasello L, et al. Phase II trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer. Anticancer Res 2005;25(2B):1391-6
  • Hwang JJ. Irinotecan and 5-FU/leucovorin in metastatic colorectal cancer: balancing efficacy, toxicity, and logistics. Oncology (Williston Park) 2004;18(14 Suppl 14):26-34
  • Fuchs CS, Marshall J, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study. J Clin Oncol 2008;26(4):689-90
  • Cartwright T, McCollum D, Boehm KA. Dosing considerations for capecitabine-irinotecan regimens in the treatment of metastatic and/or locally advanced colorectal cancer. Am J Clin Oncol 2010;33(3):307-13
  • Hirte HW, Hotte SJ. Dual-agent molecular targeting of the ErbB2 receptor: killing one bird with two stones. J Clin Oncol 2008;26(20):3301-2
  • Longo GS, Izzo J, Chang YM, et al. Pretreatment of colon carcinoma cells with Tomudex enhances 5-fluorouracil cytotoxicity. Clin Cancer Res 1998;4(2):469-73
  • Schwartz GK, Bertino J, Kemeny N, et al. Phase I trial of sequential raltitrexed followed by bolus 5-fluorouracil in patients with advanced colorectal cancer. Anticancer Drugs 2004;15(3):219-27
  • Mayer S, Vanhoefer U, Hilger T. Extended phase I study of raltitrexed and infusional 5-FU in patients with metastatic colorectal cancer. Paper presented at ASCO Meeting Abstract; New Orleans – USA; 2000
  • Farrugia DC, Aherne GW, Brunton L, et al. Leucovorin rescue from raltitrexed (tomudex)-induced antiproliferative effects: in vitro cell line and in vivo mouse studies. Clin Cancer Res 2000;6(9):3646-56
  • Hagner N, Joerger M. Cancer chemotherapy: targeting folic acid synthesis. Cancer Manag Res 2010;2:293-301
  • Avallone A, Di Gennaro E, Bruzzese F, et al. Synergistic antitumour effect of raltitrexed and 5-fluorouracil plus folinic acid combination in human cancer cells. Anticancer Drugs 2007;18(7):781-91
  • Caponigro F, Avallone A, McLeod H, et al. Phase I and pharmacokinetic study of tomudex combined with 5-fluorouracil plus levofolinic acid in advanced head and neck cancer and colorectal cancer. Clin Cancer Res 1999;5(12):3948-55
  • Comella P, De Vita F, Mancarella S, et al. Biweekly irinotecan or raltitrexed plus 6S-leucovorin and bolus 5-fluorouracil in advanced colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase II-III randomized trial. Ann Oncol 2000;11(10):1323-33
  • Gebbia V, Verderame F, Ferrau F, et al. Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas. Ann Oncol 2006;17(Suppl 7):vii60-5
  • Comella P, De Vita F, De Lucia L, et al. Oxaliplatin and raltitrexed combined with leucovorin-modulated 5-fluorouracil i.v. bolus every two weeks: a dose finding study in advanced previously treated colorectal carcinoma. Southern Italy Cooperative Oncology Group. Ann Oncol 2000;11(4):461-8
  • Comella P, Casaretti R, Crucitta E, et al. Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i.v. bolus: a salvage regimen for colorectal cancer patients. Br J Cancer 2002;86(12):1871-5
  • Avallone A, Aloj L, Delrio P, et al. Multidisciplinary approach to rectal cancer: are we ready for selective treatment strategies? Anticancer Agents Med Chem 2013;13(6):852-60
  • Teicher BA, Ara G, Chen YN, et al. Interaction of tomudex with radiation in vitro and in vivo. Int J Oncol 1998;13(3):437-42
  • Valentini V, Doglietto GB, Morganti AG, et al. Preoperative chemoradiation with raltitrexed ('Tomudex') for T2/N+ and T3/N+ rectal cancers: a phase I study. Eur J Cancer 2001;37(16):2050-5
  • Gambacorta MA, Valentini V, Morganti AG, et al. Chemoradiation with raltitrexed (Tomudex) in preoperative treatment of stage II-III resectable rectal cancer: a phase II study. Int J Radiat Oncol Biol Phys 2004;60(1):130-8
  • Gambacorta MA, Valentini V, Coco C, et al. Chemoradiation with raltitrexed and oxaliplatin in preoperative treatment of stage II-III resectable rectal cancer: phase I and II studies. Int J Radiat Oncol Biol Phys 2004;60(1):139-48
  • Valentini V, Coco C, Minsky BD, et al. Randomized, multicenter, phase IIb study of preoperative chemoradiotherapy in T3 mid-distal rectal cancer: raltitrexed + oxaliplatin + radiotherapy versus cisplatin + 5-fluorouracil + radiotherapy. Int J Radiat Oncol Biol Phys 2008;70(2):403-12
  • Caravatta L, Picardi V, Tambaro R, et al. Neoadjuvant accelerated concomitant boost radiotherapy and multidrug chemotherapy in locally advanced rectal cancer: a dose-escalation study. Am J Clin Oncol 2012;35(5):424-31
  • Caravatta L, Padula GD, Picardi V, et al. Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study. Acta Oncol 2011;50(8):1151-7
  • Avallone A, Delrio P, Guida C, et al. Biweekly oxaliplatin, raltitrexed, 5-fluorouracil and folinic acid combination chemotherapy during preoperative radiation therapy for locally advanced rectal cancer: a phase I-II study. Br J Cancer 2006;94(12):1809-15
  • Avallone A, Delrio P, Pecori B, et al. Oxaliplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: long-term outcome. Int J Radiat Oncol Biol Phys 2011;79(3):670-6
  • Avallone A, Di Gennaro E, Delrio P, et al. Neoadjuvant multidisciplinary phase II study (BRANCH) of an early bevacizumab schedule plus chemo-radiation therapy in rectal cancer: efficacy, safety, and biomarkers. Paper presented at AACR Annual Meeting Abstract; Chicago, USA; 2012
  • van Kuilenburg AB. Dihydropyrimidine dehydrogenase and the efficacy and toxicity of 5-fluorouracil. Eur J Cancer 2004;40(7):939-50
  • Dahan L, Ciccolini J, Evrard A, et al. Sudden death related to toxicity in a patient on capecitabine and irinotecan plus bevacizumab intake: pharmacogenetic implications. J Clin Oncol 2012;30(4):e41-4
  • Polk A, Vaage-Nilsen M, Vistisen K, et al. Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and predisposing factors. Cancer Treat Rev 2013;39(8):974-84
  • Twelves CJ. Xeloda in adjuvant colon cancer therapy (X-ACT) trial: overview of efficacy, safety, and cost-effectiveness. Clin Colorectal Cancer 2006;6(4):278-87
  • Wo JY, Hong TS, Kachnic LA. Impact of age and comorbidities on the treatment of gastrointestinal malignancies. Semin Radiat Oncol 2012;22(4):311-20
  • Jensen SA, Sorensen JB. Risk factors and prevention of cardiotoxicity induced by 5-fluorouracil or capecitabine. Cancer Chemother Pharmacol 2006;58(4):487-93
  • Wilson KS, Fitzgerald CA, Barnett JB, et al. Adjuvant therapy with raltitrexed in patients with colorectal cancer intolerant of 5-fluorouracil: british Columbia Cancer Agency experience. Cancer Invest 2007;25(8):711-14
  • Di Gennaro E, Bruzzese F, Pepe S, et al. Modulation of thymidilate synthase and p53 expression by HDAC inhibitor vorinostat resulted in synergistic antitumor effect in combination with 5FU or raltitrexed. Cancer Biol Ther 2009;8(9):782-91

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.