Combinations of Antimetabolites and Ionizing Radiation

  • Hiroshi Harada
  • Keiko Shibuya
  • Masahiro Hiraoka
Part of the Medical Radiology book series (MEDRAD)


Radiat Oncol Biol Phys Malignant Pleural Mesothelioma Thymidine Phosphorylase Reduce Folate Carrier Uridine Phosphorylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aherne GW et al (1996) Immunoreactive dUMP and TTP pools as an index of thymidylate synthase inhibition; effect of tomudex (ZD1694) and a nonpolyglutamated quinazoline antifolate (CB30900) in L1210 mouse leukaemia cells. Biochem Pharmacol 51:1293–1301PubMedCrossRefGoogle Scholar
  2. Allan PW, Bennett LL Jr (1971) 6-Methylthioguanylic acid, a metabolite of 6-thioguanine. Biochem Pharmacol 20:847–852PubMedCrossRefGoogle Scholar
  3. Allegra CJ et al (1985a) Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates. J Biol Chem 260:9720–9726PubMedGoogle Scholar
  4. Allegra CJ et al (1985b) Inhibition of phosphoribosylaminoimidazolecarboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates. Proc Natl Acad Sci USA 82:4881–4885PubMedCrossRefGoogle Scholar
  5. Bagshaw MA (1961) Possible role of potentiators in radiation therapy. Am J Roentgenol Radium Ther Nucl Med 85:822–833PubMedGoogle Scholar
  6. Baker CH et al (1991) 2’-Deoxy-2’-methylenecytidine and 2’-deoxy-2’,2’-difluorocytidine 5’-diphosphates: potent mechanism-based inhibitors of ribonucleotide reductase. J Med Chem 34:1879–1884PubMedCrossRefGoogle Scholar
  7. Bebenek K et al (1992) The effects of dNTP pool imbalances on frameshift fidelity during DNA replication. J Biol Chem 267:3589–3596PubMedGoogle Scholar
  8. Berry RJ (1966) Effects of some metabolic inhibitors on X-ray dose-response curves for the survival of mammalian cells in vitro, and on early recovery between fractionated X-ray doses. Br J Radiol 39:458–463PubMedCrossRefGoogle Scholar
  9. Bischof M et al (2002) Interaction of pemetrexed disodium (ALIMTA, multitargeted antifolate) and irradiation in vitro. Int J Radiat Oncol Biol Phys 52:1381–1388PubMedCrossRefGoogle Scholar
  10. Bischof M et al (2004) Triple combination of irradiation, chemotherapy (pemetrexed), and VEGFR inhibition (SU5416) in human endothelial and tumor cells. Int J Radiat Oncol Biol Phys 60:1220–1232PubMedCrossRefGoogle Scholar
  11. Blum JL (2001) The role of capecitabine, an oral, enzymatically activated fluoropyrimidine, in the treatment of metastatic breast cancer. Oncologist 6:56–64PubMedCrossRefGoogle Scholar
  12. Bruso CE et al (1990) Fluorodeoxyuridine-induced radiosensitization and inhibition of DNA double strand break repair in human colon cancer cells. Int J Radiat Oncol Biol Phys 19:1411–1417PubMedGoogle Scholar
  13. Buchsbaum DJ et al (2002) Treatment of pancreatic cancer xenografts with Erbitux (IMC-C225) anti-EGFR antibody, gemcitabine, and radiation. Int J Radiat Oncol Biol Phys 54:1180–1193PubMedCrossRefGoogle Scholar
  14. Byfield JE et al (1982) Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-Fluorouracil or ftorafur and X-rays. Int J Radiat Oncol Biol Phys 8:1923–1933PubMedGoogle Scholar
  15. Cao S et al (1999) Persistent induction of apoptosis and suppression of mitosis as the basis for curative therapy with S-1, an oral 5-fluorouracil prodrug in a colorectal tumor model. Clin Cancer Res 5:267–274PubMedGoogle Scholar
  16. Cappella P et al (2001) Cell cycle effects of gemcitabine. Int J Cancer 93:401–408PubMedCrossRefGoogle Scholar
  17. Chabner BA et al (1985) Polyglutamation of methotrexate. Is methotrexate a prodrug? J Clin Invest 76:907–912PubMedCrossRefGoogle Scholar
  18. Childs HA et al (2000) A phase I study of combined UFT plus leucovorin and radiotherapy for pancreatic cancer. Int J Radiat Oncol Biol Phys 47:939–944PubMedCrossRefGoogle Scholar
  19. Chu E et al (1996) New concepts for the development and use of antifolates. Stem Cells 14:41–46PubMedCrossRefGoogle Scholar
  20. Cooper JS et al (1999) Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. J Am Med Assoc 281:1623–1627CrossRefGoogle Scholar
  21. Crino L et al (1999) Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: a phase II trial. J Clin Oncol 17:2081–2085PubMedGoogle Scholar
  22. Doong SL, Dolnick BJ (1988) 5-Fluorouracil substitution alters pre-mRNA splicing in vitro. J Biol Chem 263:4467–4473PubMedGoogle Scholar
  23. Endo M et al (1999) Induction of thymidine phosphorylase expression and enhancement of efficacy of capecitabine or 5’-deoxy-5-fluorouridine by cyclophosphamide in mammary tumor models. Int J Cancer 83:127–134PubMedCrossRefGoogle Scholar
  24. Fujii S et al (1979) Effect of coadministration of uracil or cytosine on the anti-tumor activity of clinical doses of 1-(2-tetrahydrofuryl)-5-fluorouracil and level of 5-fluorouracil in rodents. Gann 70:209–214PubMedGoogle Scholar
  25. Fukushima M et al (1998) Anticancer activity and toxicity of S-1, an oral combination of tegafur and two biochemical modulators, compared with continuous i.v. infusion of 5-fluorouracil. Anticancer Drugs 9:817–823PubMedGoogle Scholar
  26. Gastrointestinal Tumor Study Group (1988) Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. J Natl Cancer Inst 80:751–755Google Scholar
  27. Gatzemeier U et al (1996) Activity of gemcitabine in patients with non-small cell lung cancer: a multicentre, extended phase II study. Eur J Cancer 32A:243–248PubMedCrossRefGoogle Scholar
  28. Gollin FF et al (1972) Combined therapy in advanced head and neck cancer: a randomized study. Am J Roentgenol Radium Ther Nucl Med 114:83–88PubMedGoogle Scholar
  29. Gonzalez Baron M et al (1993) Phase I study of UFT plus leucovorin in advanced colorectal cancer: a double modulation proposal. Anticancer Res 13:759–762PubMedGoogle Scholar
  30. Hall TC et al (1967) A clinical pharmacologic study of chemotherapy and X-ray therapy in lung cancer. Am J Med 43:186–193PubMedCrossRefGoogle Scholar
  31. Hanauske AR et al (2001) Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist 6:363–373PubMedCrossRefGoogle Scholar
  32. Haraguchi M et al (1994) Angiogenic activity of enzymes. Nature 368:198PubMedCrossRefGoogle Scholar
  33. Hazarika M et al (2005) Pemetrexed in malignant pleural mesothelioma. Clin Cancer Res 11:982–992PubMedGoogle Scholar
  34. Heidelberger CL et al (1958) Studies on fluorinated pyrimidines. II. Effects on transplanted tumors. Cancer Res 18:305–317PubMedGoogle Scholar
  35. Heimburger DK et al (1991) The effect of fluorodeoxyuridine on sublethal damage repair in human colon cancer cells. Int J Radiat Oncol Biol Phys 21:983–987PubMedGoogle Scholar
  36. Heinemann V et al (1988) Comparison of the cellular pharmacokinetics and toxicity of 2’,2’-difluorodeoxycytidine and 1-beta-D-arabinofuranosylcytosine. Cancer Res 48:4024–4031PubMedGoogle Scholar
  37. Heinemann V et al (1990) Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2’,2’-difluorodeoxycytidine. Mol Pharmacol 38:567–572PubMedGoogle Scholar
  38. Helsper JT, Sharp GS (1962) Combination therapy with 5-fluorouracil and cobalt-60 for inoperable carcinoma of the lungs. Cancer Chemother Rep 20:103–106PubMedGoogle Scholar
  39. Hertel LW et al (1990) Evaluation of the antitumor activity of gemcitabine (2’,2’-difluoro-2’-deoxycytidine). Cancer Res 50:4417–4422PubMedGoogle Scholar
  40. Ho DH et al (2000) Oral uracil and Ftorafur plus leucovorin: pharmacokinetics and toxicity in patients with metastatic cancer. Cancer Chemother Pharmacol 46:351–356PubMedCrossRefGoogle Scholar
  41. Hochster H et al (2005) Phase I/II dose-escalation study of pemetrexed plus irinotecan in patients with advanced colorectal cancer. Clin Colorectal Cancer 5:257–262PubMedCrossRefGoogle Scholar
  42. Hoff PM et al (2001) 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. J Clin Oncol 19:2282–2292PubMedGoogle Scholar
  43. Houghton JA et al (1995) Ratio of 2’-deoxyadenosine-5’-triphosphate/thymidine-5’-triphosphate influences the commitment of human colon carcinoma cells to thymineless death. Clin Cancer Res 1:723–730PubMedGoogle Scholar
  44. Huang P et al (1991) Action of 2’,2’-difluorodeoxycytidine on DNA synthesis. Cancer Res 51:6110–6117PubMedGoogle Scholar
  45. Ichinose Y et al (2005) UFT plus gemcitabine combination chemotherapy in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial. Br J Cancer 93:770–773PubMedCrossRefGoogle Scholar
  46. Iliakis G et al (1989) Mechanism of radiosensitization by halogenated pyrimidines: effect of BrdU on radiation induction of DNA and chromosome damage and its correlation with cell killing. Radiat Res 119:286–304PubMedGoogle Scholar
  47. Jin S, Levine AJ (2001) The p53 functional circuit. J Cell Sci 114:4139–4140PubMedGoogle Scholar
  48. Jolivet J et al (1983) The pharmacology and clinical use of methotrexate. N Engl J Med 309:1094–1104PubMedCrossRefGoogle Scholar
  49. Kanamaru R et al (1986) The inhibitory effects of 5-fluorouracil on the metabolism of preribosomal and ribosomal RNA in L-1210 cells in vitro. Cancer Chemother Pharmacol 17:43–46PubMedCrossRefGoogle Scholar
  50. Kaye SB (1994) Gemcitabine: current status of phase I and II trials. J Clin Oncol 12:1527–1531PubMedGoogle Scholar
  51. Kitazono M et al (1998) Prevention of hypoxia-induced apoptosis by the angiogenic factor thymidine phosphorylase. Biochem Biophys Res Commun 253:797–803PubMedCrossRefGoogle Scholar
  52. Kremer JM (1994) The mechanism of action of methotrexate in rheumatoid arthritis: the search continues. J Rheumatol 21:1–5PubMedGoogle Scholar
  53. Krook JE et al (1991) Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324:709–715PubMedCrossRefGoogle Scholar
  54. Kunz BA (1982) Genetic effects of deoxyribonucleotide pool imbalances. Environ Mutagen 4:695–725PubMedGoogle Scholar
  55. Latz D et al (1998) Radiosensitizing potential of gemcitabine (2’,2’-difluoro-2’-deoxycytidine) within the cell cycle in vitro. Int J Radiat Oncol Biol Phys 41:875–882PubMedCrossRefGoogle Scholar
  56. Lawrence TS et al (1996) Radiosensitization of pancreatic cancer cells by 2’,2’-difluoro-2’-deoxycytidine.” Int J Radiat Oncol Biol Phys 34:867–872PubMedCrossRefGoogle Scholar
  57. Lawrence TS et al (1997) Delayed radiosensitization of human colon carcinoma cells after a brief exposure to 2’,2’-difluoro-2’-deoxycytidine (Gemcitabine). Clin Cancer Res 3:777–782PubMedGoogle Scholar
  58. Lennard L (1992) The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol 43:329–339PubMedCrossRefGoogle Scholar
  59. Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323–331PubMedCrossRefGoogle Scholar
  60. Ling LL, Ward JF (1990) Radiosensitization of Chinese hamster V79 cells by bromodeoxyuridine substitution of thymidine: enhancement of radiation-induced toxicity and DNA strand break production by monofilar and bifilar substitution. Radiat Res 121:76–83PubMedGoogle Scholar
  61. Linke SP et al (1997) p53 mediates permanent arrest over multiple cell cycles in response to gamma-irradiation. Cancer Res 57:1171–1179PubMedGoogle Scholar
  62. Longley DB et al (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3:330–338PubMedCrossRefGoogle Scholar
  63. Malet-Martino M, Martino R (2002) Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review. Oncologist 7:288–323PubMedCrossRefGoogle Scholar
  64. Martomo SA, Mathews CK (2002) Effects of biological DNA precursor pool asymmetry upon accuracy of DNA replication in vitro. Mutat Res 499:197–211PubMedGoogle Scholar
  65. Mason KA et al (1999) Maximizing therapeutic gain with gemcitabine and fractionated radiation. Int J Radiat Oncol Biol Phys 44:1125–1135PubMedCrossRefGoogle Scholar
  66. Mendelsohn LG et al (1999) Enzyme inhibition, polyglutamation, and the effect of LY231514 (MTA) on purine biosynthesis. Semin Oncol 26(2 Suppl 6):42–47PubMedGoogle Scholar
  67. Merlin T et al (1998) Cell cycle arrest in ovarian cancer cell lines does not depend on p53 status upon treatment with cytostatic drugs. Int J Oncol 13:1007–1016PubMedGoogle Scholar
  68. Miller RC et al (2002) Acute diarrhea during adjuvant therapy for rectal cancer: a detailed analysis from a randomized intergroup trial. Int J Radiat Oncol Biol Phys 54:409–413PubMedCrossRefGoogle Scholar
  69. Mitrovski B et al (1994) Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells. Cancer Chemother Pharmacol 35:109–114PubMedCrossRefGoogle Scholar
  70. Miwa M et al (1998) 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 34:1274–1281PubMedCrossRefGoogle Scholar
  71. Moertel CG et al (1969) Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 2:865–867PubMedCrossRefGoogle Scholar
  72. Moertel CG et al (1981) Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 48:1705–1710PubMedCrossRefGoogle Scholar
  73. Moghaddam A et al (1995) Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc Natl Acad Sci USA 92:998–1002PubMedCrossRefGoogle Scholar
  74. Monnerat C et al (2004) Phase II study of pemetrexed-gemcitabine combination in patients with advanced-stage nonsmall cell lung cancer. Clin Cancer Res 10:5439–5446PubMedCrossRefGoogle Scholar
  75. Muggia FM et al (1996) Phase I and pharmacokinetic study of oral UFT, a combination of the 5-fluorouracil prodrug tegafur and uracil. Clin Cancer Res 2:1461–1467PubMedGoogle Scholar
  76. Naida JD et al (1998) The effect of activation of wild-type p53 function on fluoropyrimidine-mediated radiosensitization. Int J Radiat Oncol Biol Phys 41:675–680PubMedCrossRefGoogle Scholar
  77. O’Connell MJ et al (1994) Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 331:502–507PubMedCrossRefGoogle Scholar
  78. Oettle H et al (2005) A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol 16:1639–1645PubMedCrossRefGoogle Scholar
  79. Ostruszka LJ, Shewach DS (2000) The role of cell cycle progression in radiosensitization by 2′,2′-difluoro-2′-deoxycytidine. Cancer Res 60:6080–6088PubMedGoogle Scholar
  80. Pauwels B et al (2003) Cell cycle effect of gemcitabine and its role in the radiosensitizing mechanism in vitro. Int J Radiat Oncol Biol Phys 57:1075–1083PubMedCrossRefGoogle Scholar
  81. Pawlik TM, Keyomarsi K (2004) Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys 59:928–942PubMedCrossRefGoogle Scholar
  82. Pazdur R et al (1998) Phase I trial of uracil-tegafur (UFT) plus oral leucovorin: 28-day schedule. Cancer Invest 16:145–151PubMedGoogle Scholar
  83. Plunkett W et al (1995) Preclinical characteristics of gemcitabine. Anticancer Drugs 6(Suppl 6):7–13PubMedGoogle Scholar
  84. Robinson BW, Shewach DS (2001) Radiosensitization by gemcitabine in p53 wild-type and mutant MCF-7 breast carcinoma cell lines. Clin Cancer Res 7:2581–2589PubMedGoogle Scholar
  85. Rosenthal DI et al (2000) Postoperative radiation therapy for rectal cancer combined with UFT/leucovorin. Oncology (Williston Park) 14(10 Suppl 9):59–62Google Scholar
  86. Rosier JF et al (2004) Role of 2′-2′ difluorodeoxycytidine (gemcitabine)-induced cell cycle dysregulation in radioenhancement of human head and neck squamous cell carcinomas. Radiother Oncol 70:55–61PubMedCrossRefGoogle Scholar
  87. Rothenberg ML et al (1996) A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 7:347–353PubMedGoogle Scholar
  88. Rube CE et al (2004) Increased expression of pro-inflammatory cytokines as a cause of lung toxicity after combined treatment with gemcitabine and thoracic irradiation. Radiother Oncol 72:231–241PubMedCrossRefGoogle Scholar
  89. Sak A et al (2000) Protection of DNA from radiation-induced double-strand breaks: influence of replication and nuclear proteins. Int J Radiat Biol 76:749–756PubMedCrossRefGoogle Scholar
  90. Santi DV, Hardy LW (1987) Catalytic mechanism and inhibition of tRNA (uracil-5-) methyltransferase: evidence for covalent catalysis. Biochemistry 26:8599–8606PubMedCrossRefGoogle Scholar
  91. Santi DV, McHenry CS et al (1974) Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate. Biochemistry 13:471–481PubMedCrossRefGoogle Scholar
  92. Sato Y et al (1970) Combined surgery, radiotherapy, and regional chemotherapy in carcinoma of the paranasal sinuses. Cancer 25:571–579PubMedCrossRefGoogle Scholar
  93. Sawada N et al (1998) Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res 4:1013–1019PubMedGoogle Scholar
  94. Sawada N et al (1999) X-ray irradiation induces thymidine phosphorylase and enhances the efficacy of capecitabine (Xeloda) in human cancer xenografts. Clin Cancer Res 5:2948–2953PubMedGoogle Scholar
  95. Scagliotti GV et al (2005) Pemetrexed combined with oxaliplatin or carboplatin as first-line treatment in advanced nonsmall cell lung cancer: a multicenter, randomized, phase II trial. Clin Cancer Res 11:690–696PubMedCrossRefGoogle Scholar
  96. Schuller J et al (2000) Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol 45:291–297PubMedCrossRefGoogle Scholar
  97. Segal R et al (1990) Methotrexate: mechanism of action in rheumatoid arthritis. Semin Arthritis Rheum 20:190–200PubMedCrossRefGoogle Scholar
  98. Shewach DS, Lawrence TS (1995) Radiosensitization of human tumor cells by gemcitabine in vitro. Semin Oncol 22(4 Suppl 11):68–71PubMedGoogle Scholar
  99. Shewach DS et al (1992a) Nucleotide specificity of human deoxycytidine kinase. Mol Pharmacol 42:518–524PubMedGoogle Scholar
  100. Shewach DS et al (1992b) Decrease in TTP pools mediated by 5-bromo-2′-deoxyuridine exposure in a human glioblastoma cell line. Biochem Pharmacol 43:1579–1585PubMedCrossRefGoogle Scholar
  101. Shewach DS et al (1994) Metabolism of 2′,2′-difluoro-2′-deoxycytidine and radiation sensitization of human colon carcinoma cells. Cancer Res 54:3218–3223PubMedGoogle Scholar
  102. Shih C et al (1997) LY231514, a pyrrolo[2,3-d]pyrimidinebased antifolate that inhibits multiple folate-requiring enzymes. Cancer Res 57:1116–1123PubMedGoogle Scholar
  103. Shirasaka T et al (1993) Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its antitumor activity in rats. Cancer Res 53:4004–4009PubMedGoogle Scholar
  104. Sinclair WK (1968a) The combined effect of hydroxyurea and X-rays on Chinese hamster cells in vitro. Cancer Res 28:198–206PubMedGoogle Scholar
  105. Sinclair WK (1968b) Cyclic X-ray responses in mammalian cells in vitro. Radiat Res 33:620–643PubMedGoogle Scholar
  106. Smith TJ et al (1998) Combined chemoradiotherapy vs radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group. Int J Radiat Oncol Biol Phys 42:269–276PubMedCrossRefGoogle Scholar
  107. Sommer H, Santi DV (1974) Purification and amino acid analysis of an active site peptide from thymidylate synthetase containing covalently bound 5-fluoro-2′-deoxyuridylate and methylenetetrahydrofolate. Biochem Biophys Res Commun 57:689–695PubMedCrossRefGoogle Scholar
  108. Stein JJ, Kaufman J (1968) The treatment of carcinoma of the bladder with special reference to the use of preoperative radiation therapy combined with 5-fluorouracil. Am J Roentgenol Radium Ther Nucl Med 102:519–529PubMedGoogle Scholar
  109. Swann PF et al (1996) Role of postreplicative DNA mismatch repair in the cytotoxic action of thioguanine. Science 273:1109–1111PubMedGoogle Scholar
  110. Taguchi T (1997) Clinical application of biochemical modulation in cancer chemotherapy: biochemical modulation for 5-FU. Oncology 54(Suppl 1):12–18PubMedCrossRefGoogle Scholar
  111. Takebayashi Y et al (1996) Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma. J Natl Cancer Inst 88:1110–1117PubMedGoogle Scholar
  112. Takechi T et al (1997) Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral tegafur, in experimental tumor models in rats. Cancer Chemother Pharmacol 39:205–211PubMedCrossRefGoogle Scholar
  113. Tatsumi K et al (1987) Inhibitory effects of pyrimidine, barbituric acid and pyridine derivatives on 5-fluorouracil degradation in rat liver extracts. Jpn J Cancer Res 78:748–755PubMedGoogle Scholar
  114. Tay BS et al (1969) Inhibition of phosphoribosyl pyrophosphate amidotransferase from Ehrlich ascites-tumour cells by thiopurine nucleotides. Biochem Pharmacol 18:936–938PubMedCrossRefGoogle Scholar
  115. Tolis C et al (1999) Cell cycle disturbances and apoptosis induced by topotecan and gemcitabine on human lung cancer cell lines. Eur J Cancer 35:796–807PubMedCrossRefGoogle Scholar
  116. Van Cutsem E et al (2001) Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19:4097–4106PubMedGoogle Scholar
  117. Vermund H et al (1961) Effects of combined roentgen irradiation and chemotherapy on transplanted tumors in mice. Am J Roentgenol Radium Ther Nucl Med 85:599–607PubMedGoogle Scholar
  118. Wolmark N et al (2000) Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 92:388–396PubMedCrossRefGoogle Scholar
  119. Yoshioka A et al (1987) Deoxyribonucleoside triphosphate imbalance. 5-Fluorodeoxyuridine-induced DNA double strand breaks in mouse FM3A cells and the mechanism of cell death. J Biol Chem 262:8235–8241PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Hiroshi Harada
    • 1
  • Keiko Shibuya
    • 1
  • Masahiro Hiraoka
    • 1
  1. 1.Department of Radiation Oncology and Image-Applied Therapy, Graduate School of MedicineKyoto UniversitySakyo, KyotoJapan

Personalised recommendations