Radiotherapy & Oncology
Volume 87, Issue 3 , Pages 331-338 , June 2008

Enhanced local tumour control after single or fractionated radiation treatment using the hypoxic cell radiosensitizer doranidazole

  • Rumi Murata

      Affiliations

    • Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark
    • ,
  • Michihiko Tsujitani

      Affiliations

    • Pharmaceutical Planning Department, POLA PHARMA INC., Yokohama, Japan
    • ,
  • Michael R. Horsman

      Affiliations

    • Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark
    • Corresponding Author InformationCorresponding author. Michael R. Horsman, Department of Experimental Clinical Oncology, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark.

Received 13 August 2007 ,Revised 4 March 2008 ,Accepted 5 March 2008.

References 

  1. Moulder JE, Rockwell S. Hypoxic fractions of solid tumors: experimental techniques, methods of analysis, and a survey of existing data. Int J Radiat Oncol Biol Phys. 1984;10:695–712
  2. Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989;49:6449–6465
  3. Hoeckel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res. 1996;56:4509–4515
  4. Nordsmark M, Overgaard M, Overgaard J. Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol. 1996;41:31–39
  5. Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1997;38:285–289
  6. Horsman MR, Lindegaard JC, Grau C, Nordsmark M, Overgaard J. Dose response modifiers in radiation therapy. In:  Gunderson LL,  Tepper JE editor. Clinical radiation oncology. New York: Churchill Livingstone; 2007;p. 59–73
  7. Overgaard J, Hansen HS, Andersen AP, Hjelm-Hansen M, Jorgensen K, Sandberg E, et al. Misonidazole combined with split-course radiotherapy in the treatment of invasive carcinoma of larynx and pharynx. Final report from the DAHANCA 2 study. Int J Radiat Oncol Biol Phys. 1989;16:1065–1068
  8. Overgaard J, Hansen HS, Overgaard M, Bastholt L, Berthelsen A, Specht L, et al. A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85. Radiother Oncol. 1998;46:135–146
  9. Overgaard J, Overgaard M, Nielsen OS, Pedersen AK, Timothy AR. A comparative investigation of nimorazole and misonidazole as hypoxic radiosensitizers in a C3H mammary carcinoma in vivo. Br J Cancer. 1982;46:904–911
  10. Overgaard J. Hypoxic radiosensitization: adored and ignored. J Clin Oncol. 2007;25:4066–4074
  11. Shibamoto Y, Sakano K, Kimura R, Nishidai T, Nishimoto SI, Ono K, et al. Radiosensitization in vitro and in vivo by 3-nitrotriazoles. Int J Radiat Oncol Biol Phys. 1986;12:1063–1066
  12. Dobrowsky W, Huigol NG, Jayatilake RS, Kizilbash NIA, Okkan S, Kagiya VT, et al. AK-2123 (sanazol) as a radiation sensitizer in the treatment of stage III cervical cancer: results of an IAEA multicentre randomized trial. Radiother Oncol. 2007;82:24–29
  13. Murayama C, Suzuki A, Sato C, Tanabe Y, Shoji T, Miyata Y, et al. Radiosensitization by a new potent nucleoside analog: 1-(1′,3′,4′-trihydroxy-2′-butoxy)methyl-2-nitroimidazole(RP-343). Int J Radiat Oncol Biol Phys. 1993;26:433–443
  14. Oya N, Shibamoto Y, Sasai K, Shibata T, Murata R, Takagi T, et al. Optical isomers of a new 2-nitroimidazole nucleoside analog (PR-350 series): radiosensitization efficiency and toxicity. Int J Radiat Oncol Biol Phys. 1995;33:119–127
  15. Shibamoto Y, Kubota T, Kishii K, Tsujitani M. Radiosensitivity of human pancreatic cancer cells in vitro and in vivo, and the effect of a new hypoxic cell sensitizer, doranidazole. Radiother Oncol. 2000;56:265–270
  16. Kuno Y, Shinomiya N. PR-000350, a novel hypoxic radiosensitizer, enhances tumor cell killing by promoting apoptosis preferentially in the S-phase fraction. Apoptosis. 2000;5:69–77
  17. Aoki M, Furusawa Y, Shibamoto Y, Kobayashi A, Tsujitani M. Effect of a hypoxic cell sensitizer doranidazole on the radiation-induced apoptosis of mouse L5178Y lymphoma cells. J Radiat Res. 2002;43:161–166
  18. Mizumoto K, Qian LW, Zhang L, Nagai E, Kura S, Tanaka M. A nitroimidazole derivative, PR-350, enhances the killing of pancreatic cancer cells exposed to high-dose irradiation under hypoxia. J Radiat Res. 2002;43:43–51
  19. Yahiro T, Masui S, Kubota N, Yamada K, Kobayashi A, Kishii K. Effects of hypoxic cell radiosensitizer doranidazole (PR-350) on the radioresponse of murine and human tumor cells in vitro and in vivo. J Radiat Res. 2005;46:363–372
  20. Suzuki Y, Hasegawa M, Hayakawa K, Mitsuhashi N, Niibe H. In vivo study of radiosensitizing effect of hypoxic cell radiosensitizer PR-350 on a human small cell lung cancer. Anticancer Res. 1999;19:3993–4000
  21. Matsuoka H, Shibamoto Y, Kubota T, Tsujitani M, Majima T. In vivo efficacy and pharmacokinetics of a new hypoxic cell radiosensitizer doranidazole in SUIT-2 human pancreatic cancer xenografted in mouse pancreas. Oncol Rep. 2000;7:23–26
  22. Nemoto K, Shibamoto Y, Ohmagari J, Baba Y, Ebe K, Ariga H, et al. Phase Ia study of a hypoxic cell sensitizer doranidazole (PR-350) in combination with conventional radiotherapy. Anticancer Drugs. 2001;12:1–6
  23. Sunamura M, Karasawa K, Okamoto A, Ogata Y, Nemoto K, Hosotani R, et al. PR-350 study group. Phase III trial of radiosensitizer PR-350 combined with intraoperative radiotherapy for the treatment of locally advanced pancreatic cancer. Pancreas. 2004;28:330–334
  24. Karasawa K, Sunamura M, Okamoto A, Nemoto K, Matsuno S, Nishimura Y, et al. Efficacy of novel hypoxic cell sensitizer doranidazole in the treatment of locally advanced pancreatic cancer – long-term results of a placebo-controlled randomised study. Radiother Oncol. 2008;87:326–330
  25. Overgaard J. Simultaneous and sequential hyperthermia and radiation treatment of an experimental tumor and its surrounding normal tissue in vivo. Int J Radiat Oncol Biol Phys. 1980;6:1507–1517
  26. Horsman MR, Chaplin DJ, Overgaard J. Combination of nicotinamide and hyperthermia to eliminate radioresistant chronically and acutely hypoxic tumour cells. Cancer Res. 1990;50:7430–7436
  27. Raleigh JA, Chou SC, Arteel GE, Horsman MR. Comparisons among pimonidazole binding, oxygen electrode measurements and radiation response in C3H mouse tumors. Radiat Res. 1999;151:580–589
  28. Horsman MR, Khalil AA, Siemann DW, Grau C, Hill SA, Lynch EM, et al. Relationship between radiobiological hypoxia in tumors and electrode measurements of tumor oxygenation. Int J Radiat Oncol Biol Phys. 1994;29:439–442
  29. Grau C, Horsman MR, Overgaard J. Improving the radiation response in a C3H mouse mammary carcinoma by normobaric oxygen or carbogen breathing. Int J Radiat Oncol Biol Phys. 1992;22:415–419
  30. Horsman MR, Overgaard J. Preclinical studies on how to deal with patient intolerance to nicotinamide and carbogen. Radiother Oncol. 2004;70:301–309
  31. Hendry JH, Sutton ML. Care with radiosensitizers. Br J Radiol. 1978;51:927–928
  32. Hendry JH. Quantitation of the radiotherapeutic importance of naturally-hypoxic normal tissues from collated experiments with rodents using single doses. Int J Radiat Oncol Biol Phys. 1979;5:971–976
  33. Timothy AR, Overgaard J. In-vivo radiosensitisation by nimorazole and hyperthermia. In: Overgaard J, editor. Hyperthermic oncology 1984, volume 1. Summary papers. London: Taylor and Francis; 1984. p. 309–10.
  34. Mao HS, Grau C, Overgaard J. Interaction of misonidazole, hyperthermia, and irradiation in a C3H mammary carcinoma and its surrounding skin in vivo. Int J Radiat Oncol Biol Phys. 1991;22:115–122
  35. Denekamp J. Testing of hypoxic cell radiosensitizers in vivo. Cancer Clin Trials. 1980;3:139–148
  36. Stewart FA, Denekamp J, Randhawa VS. Skin sensitisation by misonidazole: a demonstration of uniform mild hypoxia. Br J Cancer. 1982;45:869–877
  37. Horsman MR, Siemann DW, Chaplin DJ, Overgaard J. Nicotinamide as a radiosensitizer in tumours and normal tissues: the importance of drug dose and timing. Radiother Oncol. 1997;45:167–174
  38. Murata R, Siemann DW, Overgaard J, Horsman MR. Interaction between combretastatin A-4 disodium phosphate and radiation in murine tumours. Radiother Oncol. 2001;60:155–161
  39. Hill RP. Sensitizers and radiation dose fractionation: results and interpretations. Int J Radiat Oncol Biol Phys. 1986;12:1049–1054
  40. Horsman MR, Grau C, Overgaard J. Reoxygenation in a C3H mouse mammary carcinoma: the importance of chronic rather than acute hypoxia. Acta Oncol. 1995;34:325–328
  41. Nishimura Y, Nakagawa K, Takeda K, Tanaka M, Segawa Y, Tsujino K, et al. Phase I/II trial of sequential chemotherapy using a novel hypoxic cell radiosensitizer, doranidazole (PR-350), in patients with locally advanced non-small-cell lung cancer (WJTOG-0002). Int J Radiat Oncol Biol Phys. 2007;69:786–792
  42. Overgaard J. Clinical evaluation of nitroimidazoles as modifiers of hypoxia in solid tumors. Oncol Res. 1994;6:509–518
  43. Workman P. Pharmacokinetics of hypoxic cell radiosensitizers: a review. In:  Brady LW editors. Radiation sensitizers: their use in the clinical management of cancer. New York: Masson; 1980;p. 192–206
  44. Lee D-J, Cosmatos D, Marcial VA, Fu KK, Rotman M, Cooper JS, et al. Results of an RTOG phase III trial (RTOG 85-27) comparing radiotherapy plus etanidazole (SR-2508) with radiotherapy alone for locally advanced head and neck carcinomas. Int J Radiat Oncol Biol Phys. 1995;32:567–576

PII: S0167-8140(08)00148-5

doi: 10.1016/j.radonc.2008.03.002

Radiotherapy & Oncology
Volume 87, Issue 3 , Pages 331-338 , June 2008

Article Tools

* Image Usage & Resolution