rpmjResearch'n Practical Medicine JournalResearch and Practical Medicine Journal2410-1893"QUASAR", LLC10.17709/2409-2231-2015-2-2-29-34rpmj-60Research ArticleОбзорыReviewСовременные подходы к лекарственной терапии рака мочевого пузыря после первого прогрессированияModern approaches to drug therapy of bladder cancer after first progression.БолотинаЛ. В.BolotinaL. V.

д.м.н.,  заведующая отделением химиотерапии МНИОИ им. П.А. Герцена - филиал ФГБУ «НМИРЦ» Минздрава России

PhD, MD , head of the chemotherapy Department of  P. Hertsen MORI

mnioi@mail.ruКоролеваЛ. А.KorolevaL. A.

к.м.н., врач отделения химиотерапии МНИОИ им. П.А. Герцена - филиал ФГБУ «НМИРЦ» Минздрава России

PhD, oncologist of the Department of chemotherapy of  P. Hertsen MORI

МНИОИ им. П.А. Герцена - филиал ФГБУ «НМИРЦ» Минздрава России 125284, Российская Федерация, г. Москва, 2-ой Боткинский проезд, дом 3РоссияP. Hertsen MORI 2-y Botkinskiy proezd, 3, Moskva , 125284, RussiaRussian Federation201511062015222934Copyright © Болотина Л.В., Королева Л.А., 20152015Болотина Л.В., Королева Л.А.Bolotina L.V., Koroleva L.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpmj.ru/rpmj/article/view/60

Количество цитостатиков, эффективных при раке уротелия, крайне мало. Базисным препаратом для режимов 1 линии остается цисплатин, применение которого, однако, может ограничиваться значимыми токсическими реакциями, которые развиваются у большого числа больных. В случае невозможности применения платиновых производных лечение может ограничиваться применением гемцитабина в режиме монотерапии. Значительно сложнее решать вопрос в отношении больных, прогрессирующих после 1 линии лечения. Эффективность ифосфамида,  таксанов,  топотекана,  эпитилона В,  пеметрекседа,  nab-паклитаксела, пралатрексата, таргетных препаратов или их сочетаний не оправдали возлагаемых ожиданий. 

Винфлунин  (Жавлор) – инновационный химиотерапевтический препарат оказался эффективен для терапии платинорефрактерного уротелиального рака, в том числе в исследовании 3 фазы. Мы имеем собственный положительный опыт применения Жавлора у пациента старшей возрастной группы, представленный в статье.

The number of drugs that is effective in urothelial cancer is very little. Cisplatin remains the basic drug for first line, but its use may be limited because of significant toxic reactions, that develop in a great number of patients. In case of impossibility of use of platinum derivatives treatment may be limited to the use of gemcitabine as monotherapy. It is much more difficult to resolve the issue regarding patients progressing after 1st line treatment. The effectiveness of ifosfamide, taxanes, topotecan, epitilon B, pemetrexed, nab-paclitaxel, pralatrexate, targeted drugs or their combinations had not lived up to expectations. Vinflunine (Javlor) is the innovative chemotherapeutic drug that is effective for the treatment of platinum-refractory urotelial cancer, including a phase-3 trial. We have our own positive experience with Javlor in older age group of patients, that is presented in the article

платинорефрактерный уротелиальный раквинфлунинplatinum-refractory urotelial cancervinflunineReferencesSweeney C.J., Roth B.J., Kabbinavar F.F., et al. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006; 24(21): 3451–3457.Sweeney C.J., Roth B.J., Kabbinavar F.F., et al. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006; 24(21): 3451–3457.Vaughn D.J., Broome C.M., Hussain M., et al. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002; 20 (4): 937–940.Vaughn D.J., Broome C.M., Hussain M., et al. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002; 20 (4): 937–940.Fechner G., Siener R., Reimann M., et al. Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO Trial AB 20/99). Int J Clin Pract. 2006; 60(1): 27–31.Fechner G., Siener R., Reimann M., et al. Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO Trial AB 20/99). Int J Clin Pract. 2006; 60(1): 27–31.Kanai K., Kikuchi E., Ohigashi T., et al. Gemcitabine and paclitaxel chemotherapy for advanced urothelial carcinoma in patients who have received prior cisplatin-based chemotherapy. Int J Clin Oncol. 2008; 13 (6): 510–514.Kanai K., Kikuchi E., Ohigashi T., et al. Gemcitabine and paclitaxel chemotherapy for advanced urothelial carcinoma in patients who have received prior cisplatin-based chemotherapy. Int J Clin Oncol. 2008; 13 (6): 510–514.Joly F., Houede N., Noal S., et al. Do patients with advanced urothelial carcinoma benefit from weekly paclitaxel chemotherapy? A GETUS phase II study. Clin Genitourinary Cancer. 2009; 7(2): E28-33;Joly F., Houede N., Noal S., et al. Do patients with advanced urothelial carcinoma benefit from weekly paclitaxel chemotherapy? A GETUS phase II study. Clin Genitourinary Cancer. 2009; 7(2): E28-33;Cervera Grau J. M., González-Billalabeitia E, Ayala F., et al. Long-term progression-free survival (PFS) and overall survival (OS) to pemetrexed (P) as single agent in metastatic urothelial carcinoma (MUC): A Spanish Oncology Genitourinary Group (SOGUG) systematic review. J Clin Oncol. 2012; 30(suppl; abstr 4587).Cervera Grau J. M., González-Billalabeitia E, Ayala F., et al. Long-term progression-free survival (PFS) and overall survival (OS) to pemetrexed (P) as single agent in metastatic urothelial carcinoma (MUC): A Spanish Oncology Genitourinary Group (SOGUG) systematic review. J Clin Oncol. 2012; 30(suppl; abstr 4587).Suyama T., Ueda T., Fukasawa S., et al. Combination of gemcitabine and paclitaxel as second-line chemotherapy for advanced urothelial carcinoma. Jpn J Clin Oncol. 2009; 39(4): 244–250.Suyama T., Ueda T., Fukasawa S., et al. Combination of gemcitabine and paclitaxel as second-line chemotherapy for advanced urothelial carcinoma. Jpn J Clin Oncol. 2009; 39(4): 244–250.Edeline J., Loriot Y., Culine S., et al. Accelerated MVAC chemotherapy in patients with advanced bladder cancer previously treated with a platinum-gemcitabine regimen. Eur J Cancer. 2012; 48(8):1141-1146.Edeline J., Loriot Y., Culine S., et al. Accelerated MVAC chemotherapy in patients with advanced bladder cancer previously treated with a platinum-gemcitabine regimen. Eur J Cancer. 2012; 48(8):1141-1146.Choueiri T.K., Ross R.W., Jacobus S., et al. Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum- pretreated metastatic urothelial cancer. J Clin Oncol. 2012; 30(5): 507–512.Choueiri T.K., Ross R.W., Jacobus S., et al. Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum- pretreated metastatic urothelial cancer. J Clin Oncol. 2012; 30(5): 507–512.Culine S., Theodore C., De Santis M., et al. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer. 2006; 94(10): 1395–1401.Culine S., Theodore C., De Santis M., et al. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer. 2006; 94(10): 1395–1401.Vaughn D.J., Srinivas S., Stadler W.M., et al. Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: results of a large phase 2 study. Cancer. 2009; 115: 4110–4117.Vaughn D.J., Srinivas S., Stadler W.M., et al. Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: results of a large phase 2 study. Cancer. 2009; 115: 4110–4117.Bellmunt J., Theodore C., Demkov T., et al. Phase III Trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009; 27(27): 4454–4461.Bellmunt J., Theodore C., Demkov T., et al. Phase III Trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009; 27(27): 4454–4461.Bellmunt J., Fougeray R., Rosenberg J.E., et. al. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Annals of Oncology. 2013; 24: 1466–1472.Bellmunt J., Fougeray R., Rosenberg J.E., et. al. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Annals of Oncology. 2013; 24: 1466–1472.De Santis M., Wiechno P., Lucas C. et al. Mature survival data of a randomised international phase II trial (JASINT1): vinflunine (VFL) – gemcitabine (GEM) vs vfl- CBDCA in CDDP-unfit patients (PTS) with advanced urothelial carcinoma. Annals of Oncology. 2014; 25(Suppl 4): iv280-iv304.De Santis M., Wiechno P., Lucas C. et al. Mature survival data of a randomised international phase II trial (JASINT1): vinflunine (VFL) – gemcitabine (GEM) vs vfl- CBDCA in CDDP-unfit patients (PTS) with advanced urothelial carcinoma. Annals of Oncology. 2014; 25(Suppl 4): iv280-iv304.Perez-Valderrama B., Villa J., Climent M., et al. Vinflunine maintance therapy vs best supportive care after platinum combination in advanced bladder cancer: a phase II, randomized, open label, study (MAJA), SOGUG 2011-12. Eur J Cancer. 2013; 49: 665.Perez-Valderrama B., Villa J., Climent M., et al. Vinflunine maintance therapy vs best supportive care after platinum combination in advanced bladder cancer: a phase II, randomized, open label, study (MAJA), SOGUG 2011-12. Eur J Cancer. 2013; 49: 665.

The authors declare that there are no conflicts of interest present.