Пеметрексед (алимта)


Цитировать

Полный текст

Аннотация

Пиримидины и пурины, основные строительные материалы для синтеза ДНК, всегда были перспективной мишенью для разработки новых противоопухолевых препаратов. Первым представителем семейства антиметаболитов был метотрексат, который блокировал работу фермента тетрагидрофолатредуктазы и тем самым образование тетрагидрофолата - необходимого кофактора для синтеза нуклеотидов, в частности тимидинмонофосфата. 5-Фторурацил и ралтитрексед (томудекс) ингибировали фермент тимидилатсинтетазу, необходимый для синтеза нуклеотидов. Данный обзор посвящен новому препарату из группы антиметаболитов - пеметрекседу (алимта), который продемонстрировал способность к ингибированию нескольких важных ферментов, принимающих участие в синтезе пуринов и пиримидинов.

Об авторах

С А Тюляндин

НИИ КО ГУ РОНЦ им. Н.Н.Блохина РАМН, Москва

Список литературы

  1. Hanauske A.R, Chen V., Paoletti P, Niyikiza C. Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. The Oncologist 2001, 6:363-73.
  2. Adjei A.A. Pharmacology and mechanism of action of pemetrexed. Clinical Lung Cancer 2004; 5 (suppl. 2): s51-s55.
  3. Calvert A.H. Biochemical Pharmacology of pemetrexed. Oncology 2004; 18 (suppl. 13): 13-17.
  4. Rinaldi D.A, Kuhn J.G, Burris H.A et al. A phase I evaluation of multitargeted antifolate (MTA, LY231514), administered every 21 days, utilizing the modified continual reassessment method for dose escalation. Cancer Chemother Pharmacol 1999;44:372-80.
  5. Niyikiza C, Baker S, Seitz D.E et al. Homocysteine and methylmalonic acid: markers to predict and avoid toxicity from pemetrexed therapy. Molecular Cancer Therapeutics 2002; 1: 545-52.
  6. Vogelzang N.J, Rusthoven J.J, Symanovski J et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21: 2636-44.
  7. Clarke S, Millward M, Findlay M et al. Activity of the multi - targeted antifolate MTA (LY231514) in advanced non - small cell lung cancer (NSCLC). Ann Oncol 1998;9:86.
  8. Rusthoven J, Eisenhauer E, Butts C et al. Multitargeted antifolate, LY231514, as first - line chemotherapy for patients with advanced non - small - cell lung cancer: a phase II study. J Clin Oncol 1999;17:1194-99.
  9. Smit E.F, Mattson K, Von Pawel J et al. ALIMTA(pemetrexed disodium) as second - line treatment of non - small - cell lung cancer: a phase II study. Ann. Oncol 2003; 14:455-460.
  10. Hanna N, Shepherd F.A, Fosella F.V et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non - small - cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004; 22:1589-97.
  11. Manegold C, Von Pawel J, Pirker R et al. Front - line treatment of advanced non - small cell lung cancer with MTA and cisplatin: a multicenter phase II trial. Ann Oncol 2000;11:435-40.
  12. Shepherd F.A, Dancey J, Arnold A et al. Phase II study of pemetrexed disodium, a multitargeted antifolate, and cisplatin in patients as first - line therapy in patients with advanced non - small cell lung cancer: a study of National Cancer Institute of Canada clinical trials group. Cancer 2001; 92: 595-600.
  13. Zinner R.G, Fossella F.V, Gladish G.W, Glisson B.S, Blumenschein G.R.Jr, Papadimitrakopoulou V.A, Pisters K.M, Kim E.S, Oh Y.W, Peeples B.O, Ye Z, Curiel R.E, Obasaju C.K, Hong W.K, Herbst R.S. Phase II study of pemetrexed in combination with carboplatin in the first - line treatment of advanced non - small cell lung cancer. Cancer 2005 Dec 1; 104(11): 2449-56.
  14. Scagliotti G, Kortsik C, Dark G.G et al. Pemetrexed combined with oxaliplatin or carboplatin as first - line treatment in advanced non - small - cell lung cancer: a multicenter, randomized, phase II trial. Clin Cancer Research 2005; 11:690-6.
  15. Adjei A.A, Erlichman C, Sloan J et al. A phase I and pharmacologic study of sequences of gemcitabine and the multitargeted antifolate agent LY231514 (MTA) in patients with advanced solid tumors. J Clin Oncol 2000;18:1748-57.
  16. Monnerat C, Le Chevalier T, Kelly K, Obasaju C.K, Brahmer J, Novello S, Nakamura T, Liepa A.M, Bozec L, Bunn P.A.Jr, Ettinger D.S. Phase II study of pemetrexed - gemcitabine combination in patients with advanced - stage non - small cell lung cancer. clin Cancer Res. 2004 Aug 15; 10 (16): 5439-46.
  17. Ruffie P.A: Pleural mesothelioma. Curr Opin Oncol 1991; 3:328-34.
  18. Scagliotti G.V, Shin D.M, Kindler H.L:Phase II study of pemetrexed with and without folic acid and vitamin B12 as front - line therapy in malignant pleural mesothelioma. J Clin Oncol 2003; 21(8):1556-61.
  19. Hughes A, Calvert P, Azzabi A et al: Phase I clinical and pharmacokinetic study of pemetrexed and carboplatin in patients with malignant pleural mesothelioma. J Clin Oncol 2002; 20(16):3533-44.
  20. Kindler H.L, Dugan W, Hochster H et al: Phase II Study of pemetrexed plus gemcitabine in advanced pancreatic cancer. Ammer. J Cancer 2005; 4(3): 185-91.
  21. Oettle H, Richards D, Ramanathan R.K, van Laethem J.L, Peeters M, Fuchs M, Zimmeran A, John W, Von Hoff D, Arning M, Kindler H.L. A phase III trial of pemetrexed plus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol. Oct; 16(10): 1639-45.
  22. Bajetta E, Celio L, Buzzoni R et al: Phase II study of pemetrexed disodium (Alimta) administered with oral folic in patients with advanced gastric cancer. Ann Oncol 2003; 14:1543-8.
  23. John W, Picus J, Blanke C.D et al: Activity of multitargeted antifolate (pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma: Results from a phase II study. Cancer 2000; 88:1807-13.
  24. Cripps C, Burnell M, Jolivet J et al: Phase II study of first - line LY231514 (multi - targeted antifolate) in patients with locally advanced or metastatic colorectal cancer: An NCIC Clinical Trials Group study. Ann Oncol 1999, 10:1175-79.
  25. Atkins J.N, Jacobs S.A, Wieand H.S, Smith R.E, John W.J, Colangelo L.H, Vogel V.G, Kuebler J.P, Cescon T.P, Miller B.J, Geyer C.E.Jr, Wolmark N. Pemetrexed/oxilaplatin for first - line treatment of patients with advanced colorectal cancer: a phase II trial of the National Surgical Adjuvant Breast and Bowel Projekt Foundation Research Program. Clin Colorectal Cancer 2005 Sep; 5(3): 181-7.
  26. Hochster H, Kettner E, Kroning H, Becker K, Lordick F, Ramanathan R.K, Macdonald J, Hong S, John W, Schmoll H.J. Phase I/II dose - escalation study of pemetrexed plus irinotecan in petients with advanced colorectal cancer. Clin Colorectal Cancer 2005 Nov; 5(4): 257-62.
  27. Miles D.W, Smith I.E, Coleman R.E et al. A phase II study of pemetrexed disodium (LY231514) in patients with locally recurrent or metastatic breast cancer. Eur J Cancer. Eur J Cancer 2001; 37: 1366-71.
  28. Martin M, Spielmann M, Namer M et al: Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines. Ann Oncol 2003; 14:1246-52.
  29. Llombart-Cussac A, Theodoulou M, Rowland K, et al: A phase II trial of pemetrexed disodium (ALIMTA, LY231514) in metastatic breast cancer (MBC) patients who have failed anthracyclines (A) and taxanes (T) (salvage chemotherapy) (abstract 526). Breast Cancer Res Treat 2000; 64:122.
  30. O’Shaughnessy J.A, Clark R.S, Blum J.L, Mennel R.G, Snyder D, Ye Z, Liepa A.M, Melemed A.S, Yardley D.A. Phase II study of pemetrexed in patients pretreated with an anthracycline, a taxane, and capecitabine for advanced breast cancer. Clin Breast Cancer 2005 Jun; 6(2): 143-9.
  31. Garin A, Manikhas A, Biakhov M et al. A phase II study of pemetrexed plus carboplatin as first - line therapy of patients with locally advanced or metastatic breast cancer. Proc. ASCO 2005, abs. 694.

© ООО "Консилиум Медикум", 2006

Creative Commons License
Эта статья доступна по лицензии Creative Commons Attribution-NonCommercial 4.0 International License.
 


Данный сайт использует cookie-файлы

Продолжая использовать наш сайт, вы даете согласие на обработку файлов cookie, которые обеспечивают правильную работу сайта.

О куки-файлах