New antimetabolites in cancer chemotherapy and their clinical impact

British Journal of Cancer

Volumn 78, Issue SUPPL. 1, 1998, Pages 1-7

  Kaye, S B ^a  

^a BEATSON WEST OF SCOTLAND CANCER CENTRE   (United Kingdom)

Author keywords

Antimetabolite; Cancer chemotherapy; Gemcitabine; Multi targeted antifolate; Raltitrexed

Indexed keywords

ANTINEOPLASTIC ANTIMETABOLITE;

ANIMAL; CLINICAL TRIAL; HUMAN; REVIEW;

ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; CLINICAL TRIALS; HUMANS;

EID: 0031603399     PISSN: 00070920     EISSN: None     Source Type: Journal    
DOI: 10.1038/bjc.1998.747     Document Type: Article

References (68)

1. Abbruzzese JL, Grunewald R, Weeks EA, Gravel D, Adams T, Nowak B, Mineishi S, Tarassoff P, Satterlee W and Raber MN (1991) A phase I clinical, plasma and cellular pharmacology study of gemcitabine. J Clin Oncol 9: 491-498
2. Abratt RP, Bezwoda WR, Falkson G, Goedhals L, Hacking D, Rugg TA (1994) Efficacy and safety profile of gemcitabine in non-small-cell lung cancer: a phase II study. J Clin Oncol 12: 1535-1540
3. Allegra CJ, Chabner BA, Tuazon CU, Ogata-Arakaki D, Baird B, Drake JC, Simmonds JT, Lack EE, Shelhamer JH, Balis F, Walker R, Kovacs JA, Lane HC and Masur H (1987a) Trimetrexate for the treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. N Engl J Med 117: 978-985
4. Allegra CJ, Hoang K, Yeh GC, Drake JC and Baram J (1987b) Evidence for direct inhibition of de novo purine synthesis in human MCF-7 breast cells as a principal mode of metabolic inhibition by methotrexate. J Biol Chem 262: 13520-13526
5. Anderson H, Lund F, Bach F, Thatcher N, Walling J, Hansen HH (1994) Single-agent activity of weekly gemcitabine in advanced non-small-cell lung cancer: a phase II study. J Clin Oncol 12: 1821-1826
6. Boritzki TJ, Bartlett CA, Zhang C, Howland EF, Margosiak SA, Palmer CL, Romines WH and Jackson RC (1996) AG2034: a novel inhibitor of glycinamide ribonucleotide formyltransferase. Invest New Drugs 14: 295-303
7. Burris HA III, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarrassoff P, Nelson R, Dorr FA, Stephens CD and Von Hoff DD (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15: 2403-2413
8. 10 propargyl-5,8-dideazafolic acid (CB3717) in advanced breast cancer. Eur J Cancer Clin Oncol 24: 733-736
9. Carmichael J, Possinger K, Philip P, Beykirch M, Kerr H, Walling J and Harris AL (1995) Advanced breast cancer: a phase II trial with gemcitabine. J Clin Oncol 13: 2731-2736
10. Clarke S, Boyer M, Milward M, Findlay M, Ackland S, Childs A, Brew S and Walcher V (1997) Phase II study of LY231514, a multitargeted antifolate (MTA), in patients with advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 16: 465:A1670
11. Clendininn NJ and Johnston A (1996) Phase II trials of Thymitaq™ (AG337) in six solid tumor diseases. Ann Oncol 7 (suppl. 1): 86
12. Cripps MC, Burnell M, Jolivet J, Lofters W, Fisher B, Panasci L, Iglesias J and Eisenhauer E (1997) Phase II study of a multi-targeted antifolate (LY231514) (MTA) as first-line therapy in patients with locally advanced or metastatic colorectal cancer (MCC). Proc Am Soc Clin Oncol 16: 267: A949
13. Faessel H, Slocum HK, Jackson RC, Boritzki T, Rustum YM and Greco WR (1996) Super in vitro synergy between trimetrexate and the polyglutamylatable antifolates AG2034, AG2032, AG2009 and tomudex against human HCT-8 colon cells. Proc Am Assoc Cancer Res 37: A2629
14. Farber S, Diamond LK, Mercer RD, Sylvester RF and Wolff JA (1948) Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid (aminopterin). N Engl J Med 238: 787-793
15. Feun LG, Savaraj N, Benedtto P, Hanlon J, Sridhar KS, Collier M, Richman S, Liao SH and Clendeninn NJ (1991) Phase I trial of piritrexim capsules using prolonged low-dose oral administration for the treatment of advanced malignancies. J Natl Cancer Inst 83: 51-55
16. Gorlick R, Goker E, Trippett T, Waltham M, Banerjee D and Bertino JR (1996) Intrinsic and acquired resistance to methotrexate in acute leukemia. N Engl J Med 335: 1041-1048
17. Hausknecht RU (1995) Methotrexate and misoprostol to terminate early pregnancy, N Engl J Med 333: 537-540
18. Hertel LW, Kroin JS, Misner JW and Tustin JM (1988) Synthesis of 2-deoxy-2,2-difluoro-D-ribose and 2-deoxy-2,2-difluoro-D-ribofuranosyl nucleotides. J Org Chem 53: 2406-2409
19. Hoffmeister RT (1983) Methotrexate therapy in rheumatoid arthritis: 15 years experience. Am J Med 30: 69-73
20. Huang P, Chubb S, Hertel LW, Grindey GB and Plunkett W (1991) Action of 2′,2′-difluorodeoxycytidine on DNA synthesis. Cancer Res 51: 6110-6117
21. Hughes M, Planting A, Twelves C, Schellens J, Allman D, Osterwalder B, Kaye S and Verweij J (1996) A phase I study of intermittent twice daily oral therapy with capecitabine in patients with advanced and/or metastatic solid cancer. Ann Oncol 7 (suppl. 1): 87
22. Jackman AL, Kimbell R, Brown M, Brunton L, Harrap KR, Wardleworth JM and Boyle FT (1995) The antitumour activity of ZD9331, a non-polyglutamatable quinazoline thymidylate synthase inhibitor. Adv Exp Med Biol 370: 185-188
23. John W, Clark J, Burris H, Picus J, Schulman L, Thornton D and Lochrer P (1997) A phase II trial of LY231514 in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 16: 292: A1038
24. Johnston PG, Fisher ER, Rockette HE, Fisher B, Wolmark N, Drake JC, Chabner BA and Allegra CJ (1994) The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer. J Clin Oncol 12: 2640-2647
25. Johnston PG, Mick R, Recant W, Behan KA, Dolan ME, Ratain MJ, Beckmann E, Weichselbaum RR, Allegra CJ and Vokes EE (1997) Thymidylate synthase expression and response to neoadjuvant chemotherapy in patients with advanced head and neck cancer. J Natl Cancer Inst 89: 308-313
26. Jolivet J, Cowen KH, Curt GA, Clendeninn NJ and Chabner BA (1983) The pharmacology and clinical use of methotrexate. N Engl J Med 309: 1094-1104
27. Jones TR, Calvert AH, Jackman AL, Brown SJ, Jones M and Harrap KR (1981) A potent antitumour quinazoline inhibitor of thymidylate synthase: synthesis, biological properties and therapeutic results in mice. Eur J Cancer 17: 11-19
28. Kay AC, Saven A, Carrera CJ, Carson DA, Thurston D, Beutler E and Piro LD (1992) 2-Chlorodeoxyadenosine treatment of low-grade lymphomas. J Clin Oncol 10: 371-377
29. Kaye SB (1994) Gemcitabine: current status of phase I and II trials. J Clin Oncol 12: 1527-1531
30. Keating MJ, McCredie KB, Bodey GP, Smith TL, Gehan E and Freireich EJ (1982) Improved prospects for long term survival in adults with acute myelogenous leukemia. J Am Med Assoc 248: 2481-2486
31. Kelland LR, Abel G, Brown M and Jackman AL (1992) Cytotoxicity of ICI D 1694 and cisplatin in sensitive and acquired resistant tumor cell lines. Br J Cancer 65: 64
32. Laohavinij S, Wedge SR, Lind MJ, Bailey N, Humphreys A, Proctor M, Chapman F, Simmons D, Oakley A, Robson L, Gumbrell L, Taylor GA, Thomas HD, Boddy AV, Newell DR and Calvert AH (1996) A phase I clinical study of the antipurine antifolate lometrexol (DDATHF) given with oral folic acid. Invest New Drugs 14: 325-335
33. Leichman L, Lenz HJ, Leichman CG, Groshen S, Danenberg K, Baranda J, Spears CP, Boswell W, Silberman H, Ortega A, Stain S, Beart R and Danenberg P (1995) Quantitation of intratumoral thymidylate synthase expression predicts for resistance to protracted infusion of 5-fluorouracil and weekly leucovorin in disseminated colorectal cancers: preliminary report from an ongoing trial. Eur J Cancer 31A: 1306-1310
34. Lenz H-J, Leichman CG, Danenberg KD, Danenberg PV, Groshen S, Cohen H, Laine L, Crookes P, Silberman H, Baranda J, Garcia Y, Li J and Leichman L (1996) Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol 14 (1): 176-182
35. McDonald CJ (1981) The uses of systemic chemotherapeutic agents in psoriasis. Pharmacol Ther 14: 1-24
36. McDonald AC, Vasey PA, Walling J, Lindb MJ, Bailey NP, Siddiquib C, Twelves J, Cassidy J and Kaye SB (1996) Clinical phase I study of LY231514, a multitargeted anti-folate, administered by daily x 5 q 21 schedule. Ann Oncol 7 (suppl. 1): 85
37. Marshall JL and Delap RJ (1994) Clinical pharmacokinetics and pharmacology of trimetrexate. Clin Pharm 26: 190-200
38. Mendelsohn LG, Gates SB, Habeck LL, Shackelford KA, Worzalla J, Shih C and Grindey GB (1996a) The role of dietary folate in modulation of folate receptor expression folylpolyglutamate synthetase activity and the efficacy and toxicity of lometrexol. Adv Enzyme Regul 36: 365-381
39. Mendelsohn LG, Shih C, Schultz RM, Worzalla JF (1996b) Biochemistry and pharmacology of glycinamide ribonucleotide formyltransferase inhibitors: LY309887 and lometrexol. Invest New Drugs 14(3): 287-294
40. Miller KD, Loehrer PJ, Picus J, Blanke C, John W, Clark J, Shulman L, Burris H and Thornton D (1997) A phase II trial of LY231514 in patients with unresectable pancreatic cancer. Proc Am Soc Clin Oncol 16: 297: A1060
41. 4-trimethoxybenzoyl-5′-deoxy-5-fluorocytidine and its parent drug 5′-deoxy-5-fluorouridine. Chem Pharm Bull 36: 998-1003
42. Moertel CG (1978) Chemotherapy of gastrointestinal cancer. N Engl J Med 299: 1049-1052
43. Pazdur R and Vincent M (1997) 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. Proc Am Assoc Cancer Res 16: A2228
44. Pestalozzi BC, Peterson HF, Gelber RD, Goldhirsch A, Gusterson BA, Thrihia H, Lindtner J, Cortes-Funes H, Simmoncini E, Byrne MJ, Golouh R, Rudenstam CM, Castiglione-Gertsch M, Allegra CJ and Johnston PG (1997) Prognostic importance of thymidylate synthase expression in early breast cancer. J Clin Oncol 15: 1923-1931
45. Pinedo HM, Zaharko DS, Bull JM and Chabner BA (1976) The reversal of methotrexate cytotoxicity to mouse bone marrow cells by leucovorin and nucleosides. Cancer Res 36: 4418-1424
46. Pollera CF, Ceribelli A, Crecco M and Calabresi F (1994) Weekly gemcitabine in advanced bladder cancer: a preliminary report from a phase I study. Ann Oncol 5(2): 182-184
47. Porter DJT, Chestnut WG, Merrill BM and Spector T (1992) Mechanism-based inactivation of dihydropyrimidine dehydrogenase by 5-ethynyluracil. J Biol Chem 267: 5236-5242
48. Ray MS, Muggia FM, Leichman CG, Grunberg SM, Nelson RL, Dyke RW and Moran RG (1993) Phase I study of (6R)-5,10-dideazatetrahydrofolate: a folate anti-metabolite inhibitory to de novo purine synthesis. J Natl Cancer Inst 85: 1154-1159
49. Richel DJ, Colly LP, Lurvink E and Willemze R (1988) Comparison of the antileukaemic activity of 5-aza-2-deoxycytidine and arabinofuranosylcytosine in rats with myelocytic leukaemia. Br J Cancer 58: 730-733
50. Rinaldi DA, Burris HA, Dorr FA, Woodworth JR, Kuhn JG, Eckardt JR, Rodriguez G, Corso SW, Fields SM and Langley C (1995) Initial phase I evaluation of the novel thymidylate synthase inhibitor, LY231514, using the modified continual reassessment method for dose escalation. J Clin Oncol 13: 2842-2850
51. Rinaldi DA, Burris HA, Dorr FA, Rodriguez G, Eckardt JR, Fields SM, Woodworth JR, Kuhn JG, Langley C, Clark G, Lu P and Von Hoff DD (1996) A phase I evaluation of LY231514, a novel multi-targeted antifolate, administered every 21 days. Proc Am Soc Clin Oncol 15: A1559
52. Rusthoven J, Eisenhauer E, Butts C, Gregg R, Dancey J, Fisher B and Iglesias J (1997) A phase II study of the multi-targeted antifolate LY231514 in patients with advanced non-small cell lung cancer. Proc Am Soc Clin Oncol 16: 480: A1728
53. Schüller J, Cassidy J, Reigner BG, Durston S, Roos B, Ishitsuka H, Utoh M and Durmont E (1997) Tumour selectivity of Xeloda™ in colorectal cancer patients. Proc ASCO 16: 227a
54. Schultz R, Andis S, Chen V, Mendelsohn L, Patel V, Shih C and Houghton J (1996) Comparative antitumor activity of the multitargeted antifolate LY231514 and the thymidylate synthase inhibitor ZD1694. NCI Symp New Drugs Cancer Ther Ann Oncol 7(suppl. 1): A290
55. 10-propargyl-5,8-dideazafolic acid, CB3717. Eur J Cancer Clin Oncol 24: 769-775
56. Shih C, Chen VJ, Gossett LS, Yates SB, MacKellar WC, Habeck LL, Shackelford KA, Mendelsohn LG, Soose DJ, Patel VF, Andis SL, Bewley JR, Rayl EA, Morosen BA, Beardsley GP, Kohler W, Ratnam M and Schultz RM (1997) LY231514, a Pyrrolo[2.3d]-pyrimidine based antifolate that inhibits multiple folate requiring enzymes. Cancer Res 57: 1116-1123
57. Sirotnak FM, Degraw JI, Schmid FA, Goutas LJ, Moccio DM, Samuels LL and Goutes LJ (1984) New folate analogs of the 10-deaza-aminopterin series. Basis for structural design and biochemical and pharmacologic properties. Cancer Chemother Pharmacol 12: 18-25
58. Smith IE, Spielmann M, Bonneterre J, Namer M, Green M, Wandar HE, Toussaint C and Azab M (1994) Tomudex (ZD1694), a new thymidylate synthase inhibitor with antitumour activity in breast cancer. Ann Oncol 5 (suppl. 5): A242
59. Smith IE, Miles DW, Coleman RE, Lind MJ, McCarthy S and Chick J (1997) Phase II study of LY231514 (MTA) in patients (pts) with locally recurrent or metastatic breast cancer (LR/MBC) - an interim report. Proc Am Soc Clin Oncol 16: 191: A671
60. Stephens TC, Smith MN and McCloskey ML (1994) ZD9331 a novel non-polyglutamated thymidylate synthase inhibitor: in vivo antitumour efficacy and toxicity to normal murine tissues. Proc Am Assoc Cancer Res 35: A1896
61. Steward WP (1997) Combination studies with gemcitabine in the treatment of non-small-cell lung cancer (NSCLC): Br J Cancer (this issue)
62. Takemura Y and Jackman AL (1997) Folate-based thymidylate synthase inhibitors in cancer chemotherapy. Anti-Cancer Drugs 8: 3-16
63. Taylor EC, Kuh D (1992) A dideazatetrahydrofolate analogue lacking a chiral center at C-6, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl] benzoyl]-L-glutamic acid, is an inhibitor of thymidylate synthase. J Med Chem 35: 4450-4454
64. Van der Wilt CL, Pinedo HM, Smid K and Peters GJ (1992) Elevation of thymidylate synthase following 5-fluorouracil treatment is prevented by the addition of leucovorin in murine colon tumors. Cancer Res 52: 2922-2928
65. Webber SE, Bleckman TM, Attard J, Deal JG, Kathardekar V, Welsh KM, Webber S, Janson CA, Matthews DA and Smith WW (1993) Design of thymidylate synthase inhibitors using protein crystal structures: the synthesis and biological evaluation of a novel class of 5-substituted quinazolinones. J Med Chem 36: 733-746
66. Webber S, Bartlett CA, Boritzki TJ, Hillard JA, Howland CF, Johnston AL, Koda M, Margosiak SA, Morse CA and Shetty BV (1996) AG337, a novel lipophilic thymidylate synthase inhibitor: in vitro and in vivo pre-clinical studies. Cancer Chemother Pharmacol 37: 509-517
67. Zalcberg JR, Cunningham D, Van Cutsem E, Francois E, Schornagel J, Adenis A, Green M, Iveson A, Azab M and Seymour I (1996) ZD1694: a novel thymidylate synthase inhibitor with substantial activity in the treatment of patients with advanced colorectal cancer. J Clin Oncol 14: 716-721
68. Zalcberg JR, Ibrahaim J, Johnston PG, Locker GY, O'Dwyer PJ, Weiner LM, Hochster HS, Rao S and Benson AB (1997) ECOG phase II study of Tomudex® in advanced colorectal cancer. Proc Am Assoc Cancer Res 16: A268