Ftorafur®. Perspektivy primeneniya v sovremennoy klinicheskoy onkologii


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Abstract

Идея создания или достижения постоянной максимально высокой концентрации 5-фторурацила (5-ФУ) в клетках опухоли привела к клинической разработке метода его длительных инфузий. В настоящее время доказано, что, по сравнению с болюсным, инфузионное введение 5-ФУ сопровождается снижением частоты и тяжести гематологической и гастроинтестинальной токсичности и, по данным ряда исследований, увеличением эффективности лечения [1, 2]. К недостаткам метода следует отнести необходимость катетеризации центральной вены, использование оборудования для инфузий, повышенный риск развития инфекционных осложнений. Как было показано в ряде исследований, прием внутрь производных 5-ФУ является адекватной альтернативой его длительным инфузиям. Использование таблетированных форм более перспективно, так как при сохранении лечебной активности в этом случае существенно снижается частота побочных реакций, экономится время медицинского персонала, появляется возможность безопасно проводить химиотерапию в амбулаторных условиях и, при прочих равных условиях, таблетированную форму наиболее предпочитают больные. В настоящее время в режимах химиотерапии применяют капецитабин, Фторафур (Тегафур), его комбинацию с урацилом – UFT и др. Первым, в 1980-е гг., в клиническую практику вошел Фторафур.Целью настоящего сообщения является обзор ряда перспектив применения Фторафура в клинической практике.

About the authors

S L Gutorov

ГУ РОНЦ им. Н.Н.Блохина РАМН, Москва

Отделение химиотерапии и комбинированного лечения злокачественных опухолей

References

  1. Meta-Analysis Group in Cancer. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 1998; 16: 301–8.
  2. Meta-Analysis Group in Cancer. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol 1998; 16: 3537–41.
  3. Au J.L, Sadee W. The pharmacology of ftorafur (R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil). Recent Res Cancer Res 1981; 76: 100–14.
  4. Au J.L, Wu A.T, Friedman M.A, Sadee W. Pharmacokinetics and metabolism of ftorafur in man. Cancer Treat Rep 1979; 63: 343–50.
  5. Anttila M.I, Sotaniemi E.A, Kairaluoma M.I et all. Pharmacokinetics of ftorafur after intravenous and oral administration. Cancer Chemother Pharmacol 1983; 10: 150–3.
  6. Komatsu T, Yamazaki H, Shimada N et al. Involvement of Microsomal Cytochrome P450 and Cytosolic Thymidine Phosphorylase in 5-Fluorouracil Formation from Tegafur in Human Liver. Clinical Cancer Research, March 2001; 7: 675–81.
  7. Anttila M.I, Sotaniemi E.A, Kairaluoma et al. Pharmacokinetics of ftorafur after intravenous and oral administration. Cancer Chemother Pharmacol 1983; 10: 150–3.
  8. Блохин Н.Н., Переводчикова Н.И. Химиотерапия опухолевых заболеваний. М.: Медицина, 1984; 82.
  9. Апинис Т.А., Мейрена Д.В., Гилев А.П. и др. Экспериментальная и клиническая фармакотерапия. Рига: Зинатне, 1977; Вып. 7: 93–9.
  10. Grem J.L. 5-Fluoropyrimidines. Cancer Chemotherapy and Biotherapy. B.A.Chabner, D.L.Longo (eds.). 2nd ed, Philadelphia: Lippincott-Raven Publishers, 1996; 149–211.
  11. Ansfield F.J, Kallas G.J, Singson J.P. Phase I-II studies of oral tegafur (ftorafur). J Clin Oncol 1983; 1: 107–10.
  12. Wolmark N, Rockette H, Fisher B et al. The benefit of leucovorin - modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-03. J Clin Oncol 1993; 11: 1879–87.
  13. International Multicenter Pooled Analysis of Colon Cancer Trials (IMPACT) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet 1995; 345: 939–44.
  14. Advanced Colorectal Cancer Meta - analysis Project. Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. J Clin Oncol 1992; 10: 896–903.
  15. Nogue M, Saigi E, Segui M.A. Clinical experience with tegafur and low dose oral leucovorin: a dose - finding study. Oncology 1995; 52: 167–9.
  16. Andersen E, Pedersen H. Oral ftorafur versus intravenous 5-fluorouracil. Acta Oncol 1987; 26: 433–6.
  17. Bjerkeset T, Fjosne H.E. Comparison of oral ftorafur and intravenous 5-fluorouracil in patients with advanced cancer of the stomach, colon, or rectum. Oncology (Basel) 1986; 43: 212–215 Kajanti M.J, Pyrhonen S, Maiche A. Oral tegafur in the treatment of metastatic breast cancer: Phase II study. Eur J Cancer 1993; 29A: 863–6.
  18. Palmeri S, Gebbia V, Russo A et al. Oral tegafur in the treatment of gastrointestinal tract cancers: a Phase II study. Br J Cancer 1990; 61: 475–8.
  19. Gonzalez-Baron M, Vicente J, Tomas M et al. Phase II trial of cisplatin and tegafur as initial therapy in squamous - cell carcinoma of the head and neck. Am J Clin Oncol 1990; 13 (4): 312–4.
  20. Gonzalez-Larriba J.L, Garcia Carbonero I, Sastre Valera J et al. Neoadjuvant therapy with cisplatin/fluorouracil vs cisplatin/UFT in locally advanced squamous cell head and neck cancer. Oncology (Huntingt) 1997; 11 (suppl. 10): 90–7.
  21. Calvo F.A, Matute R, Garcia-Sabrido J.L et al. Neoadjuvant Chemoradiation With Tegafur in Cancer of the Pancreas: Initial Analysis of Clinical Tolerance and Outcome. American Journal of Clinical Oncology. August 2004; 27 (4): 343–9.
  22. Ulrich-Pur H, Raderer M, Kornek G.V et al. Treatment of Advanced Gastric Cancer with Oral Idarubicin, Leucovorin, and Tegafur. Onkologie 1999; 22: 292–4.
  23. Kurihara M, Izumi T, Yoshida S et al. A cooperative randomized study on tegafur plus mitomycin C versus combined tegafur and uracil plus mitomycin C in the treatment of advanced gastric cancer. Jpn J Cancer Res 1991; 82: 613–20.
  24. Sasagawa T, Ho N, Endo T et al. Randomized controlled trial of MMC + UFT and MMC + 5-FU therapy in advanced gastric cancer. Jpn J Cancer 1994; 21: 1179–85.
  25. Jin M, Yang B, Zhang W et al. High - dose mitomycin C-containing regimens in the treatment of advanced gastric cancer. Semin Surg Oncol 1994; 10: 114–6.
  26. 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.
  27. Cirera L, Balil A, Batiste-Alentorn E et al. Randomized clinical trial of adjuvant mitomycin plus tegafur in patients with resected stage III gastric cancer. J Clin Oncol 1999; 17 (12): 3810–5.
  28. Arima S, Ohsato K, Hisatsugu T et al. Multicentre randomized study of adjuvant chemotherapy with mitomycin C and tegafur or tegafur - uracil in gastric cancer. Eur J Surg 1994; 160: 227–32.
  29. Andersen E, Pedersen H. Oral ftorafur versus intravenous 5-fluorouracil. A comparative study in patients with colorectal cancer. Acta Oncol 1987; 26: 433–6.
  30. Bedikian A.Y, Stroehlein J, Korinek J et al. A comparative study of oral tegafur and intravenous 5-fluorouracil in patients with metastatic colorectal cancer. Am J Clin Oncol 1983; 6: 181–6.
  31. Losa A.F, Cirera L, Mendez M et al. Randomized phase IV trial of oral tegafur and low dose leucovorin versus intravenous 5-fluorouracil and leucovorin in the treatment of advanced colorectal cancer (ACC): Final results. ASCO 2004, J Clin Oncol 2004; 23: ab 3547.
  32. Pazdur R, Douillard J-Y, Skillings J.R et al. Multicenter phase III study of 5-fluorouracil (5-FU) or UFT™ in combination with leucovorin (LV) in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 1999; 18: 1009a.
  33. Carmichael J, Popiela T, Radstone D et al. Randomized comparative study of OrzelR (oral Uracil/Tegafur (UFT™) plus leucovorin (LV)) versus parenteral 5-fluorouracil (5-FU) plus LV in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 1999; 18: 1015a.
  34. Borner M.M, Schoffski P, de Wit R et al. Patient preference and pharmacokinetic of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer 2002; 38: 349–58.
  35. 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.
  36. Yoshikawa R, Kusunoki M, Yanagi H et al. New chemotherapeutic strategy for colorectal cancer by "pharmacokinetic modulating chemotherapy (PMC)". Proc Am Soc Clin Oncol 2001; 20: 3085a.
  37. Yoshikawa R, Kusunoki M, Yanagi H et al. Dual antitumor effects of 5-fluorouracil on the cell cycle in colorectal carcinoma cells: a novel target mechanism concept for pharmacokinetic modulating chemotherapy. Cancer Res 2001; 61: 1029–37.
  38. Yamagi H, Kusunoki M, Yoshikawa R et al. Clinical results of pharmacokinetic modulating chemotherapy (PMC) in combination with hepatic arterial 5-FU infusion and oral UFT after resection of hepatic colorectal metastases. Proc Am Soc Clin Oncol 2001; 20: 556a.
  39. Guangchuan X.U, Tiehua R.O.N.G, Peng L.I.N et al. Adjuvant chemotherapy following radical surgery for non - small - cell lung cancer: a randomized study on 70 patients. Chinese Medical Journal 2000; 113 (7): 617–20.
  40. Tashiro H, Nomura Y, Ohsaki A. A double blind comparative study of tegafur (FT) and UFT (a combination of tegafur and uracil) in advanced breast cancer. Jpn J Clin Oncol 1994; 24: 212–7.
  41. Iglesias L, Moreno J.A, Torrija E et al. UFT in combination as adjuvant therapy for breast cancer. Grupo Oncologico de Sevilla, Seville, Spain. Oncology (Huntingt) 1997; 11 (suppl. 10): 74–81.
  42. Hata Y, Uchino J, Asaishi K et al. UFT and mitomycin plus tamoxifen for stage II, ER-positive breast cancer. Hokkaido ACETBC Study Group. Oncology (Huntingt) 1999; 13 (suppl. 3): 91–5.
  43. Sugimachi K, Maehara Y, Akazawa K et al. Postoperative chemo - endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor - positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer. Breast Cancer Res Treat 1999; 56: 113–24.
  44. Galmarini C.M, Garbovesky C, Galmarini D et al. Oral ftorafur plus intramuscular thiotepa as adjuvant chemotherapy in patients with breast cancer. Med Oncol 2002; 19 (4): 227–32.

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