Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press18310.17650/1994-4098-2011-0-3-83-87GYNECOLOGY. TREATMENTГИНЕКОЛОГИЯ. ЛЕЧЕНИЕDrug treatment for cancer of the corpus uteri: Protracted stagnation or breakthrough expectationЛекарственное лечение рака тела матки — затянувшаяся стагнация или ожидание прорыва?ArtamonovaE. V.АртамоноваЕ. В.
Russian Federation
artamonovae@mail.ruN.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, MoscowРассматриваются особенности течения и терапии рака тела матки на основании некоторых клинико-биологических характеристик опухоли. Цель проводимых и будущих клинических исследований — расширение арсенала активных лекарственных агентов и индивидуализация терапии больных раком эндометрия.140820113838718082014180820142011https://ojrs.abvpress.ru/ojrs/article/view/183

The paper considers the specific features of the course and therapy of cancer of the corpus uteri on the basis of some clinical and biological characteristics of the tumor. The objective of ongoing and future clinical trials is to expand the arsenal of active drugs and to individualize therapy in patients with endometrial cancer.

Рассматриваются особенности течения и терапии рака тела матки на основании некоторых клинико-биологических характе- ристик опухоли. Цель проводимых и будущих клинических исследований — расширение арсенала активных лекарственных агентов и индивидуализация терапии больных раком эндометрия.

endometrial cancermolecular genetic markerstreatmentрак эндометриямолекулярно-генетические маркерылечение1. http://www.cancer.org/acs/groups/ content/@epidemiologysurveilance/ documents/document/acspc-027766.pdf (GLOBOCAN 2008 (IARC) — Section of Cancer Information (6/3/2011); pp. 3−7.http://www.cancer.org/acs/groups/ content/@epidemiologysurveilance/ documents/document/acspc-027766.pdf (GLOBOCAN 2008 (IARC) — Section of Cancer Information (6/3/2011); pp. 3−7.2. Sorosky J.I. Endometrial cancer. Obstet Gynecol 2008;111:436−47.Sorosky J.I. Endometrial cancer. Obstet Gynecol 2008;111:436−47.3. Hecht J.L., Mutter G.L. Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol 2006;24:4783−91.Hecht J.L., Mutter G.L. Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol 2006;24:4783−91.4. Mutter G.L. PTEN, a protean tumor suppressor. Am J Pathol 2001; 158:1895−8.Mutter G.L. PTEN, a protean tumor suppressor. Am J Pathol 2001; 158:1895−8.5. Mutter G.L., Lin M.C., Fitzgerald J.T. et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000;92:924−30.Mutter G.L., Lin M.C., Fitzgerald J.T. et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000;92:924−30.6. Maxwell G.L., Risinger J.I., Gumbs C. et al. Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias. Cancer Res 1998;58:2500−3.Maxwell G.L., Risinger J.I., Gumbs C. et al. Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias. Cancer Res 1998;58:2500−3.7. Bansal N., Yendluri V., Wenham R.M. et al. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control 2009;16:8−13.Bansal N., Yendluri V., Wenham R.M. et al. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control 2009;16:8−13.8. Delmonte A., Sessa C. Molecule-targeted agents in endometrial cancer. Curr Opin Oncol 2008;20:554−9.Delmonte A., Sessa C. Molecule-targeted agents in endometrial cancer. Curr Opin Oncol 2008;20:554−9.9. Lax S., Kendall B., Tashiro H. et al. The frequency of p53, K-ras mutation and microsatellite instability differs in uterine endometrioid and serous carcinoma: Evidence of distinct molecular genetic pathways. Cancer 2000;88:814−24.Lax S., Kendall B., Tashiro H. et al. The frequency of p53, K-ras mutation and microsatellite instability differs in uterine endometrioid and serous carcinoma: Evidence of distinct molecular genetic pathways. Cancer 2000;88:814−24.10. Basil J.B., Goodfellow R.J., Rader J.S. et al. Clinical significance of microsatellite instability in endometrial carcinoma. Cancer 2000;89:1758−64.Basil J.B., Goodfellow R.J., Rader J.S. et al. Clinical significance of microsatellite instability in endometrial carcinoma. Cancer 2000;89:1758−64.11. Bilbao C. The relationship between microsatellite instability and PTEN gene mutations in endometrial cancer. Int J Cancer 2006;119:563−70.Bilbao C. The relationship between microsatellite instability and PTEN gene mutations in endometrial cancer. Int J Cancer 2006;119:563−70.12. Saegusa M., Hasimura M., Yoshida T. et al. Beta-catenin mutations and aberrant nuclear expression during endometrial tumorigenesis. Br J Cancer 2001;84:209−17.Saegusa M., Hasimura M., Yoshida T. et al. Beta-catenin mutations and aberrant nuclear expression during endometrial tumorigenesis. Br J Cancer 2001;84:209−17.13. Moreno-Bueno G., Hardisson D. et al. Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene 2002;21:7981−90.Moreno-Bueno G., Hardisson D. et al. Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene 2002;21:7981−90.14. Doll A., Abal M., Rigau M. et al. Novel molecular profiles of endometrial cancer- new light through old windows. J Steroid Biochem Mol Biol 2008;108:221−9.Doll A., Abal M., Rigau M. et al. Novel molecular profiles of endometrial cancer- new light through old windows. J Steroid Biochem Mol Biol 2008;108:221−9.15. Dizon D.S., Lu K.H., Miller D.S. Endometrial cancer: present state and future promise. Proc. ASCO 2011. Ed. Book; pp. 205−10.Dizon D.S., Lu K.H., Miller D.S. Endometrial cancer: present state and future promise. Proc. ASCO 2011. Ed. Book; pp. 205−10.16. Perry M.C., ed. The chemotherapy source book, 4rd ed. Philadelphia: Lippincutt Williams & Wilkins; p.447−50.Perry M.C., ed. The chemotherapy source book, 4rd ed. Philadelphia: Lippincutt Williams & Wilkins; p.447−50.17. Thigpen J.T., Brady M.F., Homesley H.D. et al. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 2004;22 (19):3902−8.Thigpen J.T., Brady M.F., Homesley H.D. et al. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 2004;22 (19):3902−8.18. Fleming G.F., Filiaci V.L., Bentley R.C. et al. Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol 2004; 15 (8):1173−8.Fleming G.F., Filiaci V.L., Bentley R.C. et al. Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol 2004; 15 (8):1173−8.19. Fleming G.F., Brunetto V.L., Cella D. et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: A Gynecologic Oncology Group study. J Clin Oncol 2004; 22(11):2159−66.Fleming G.F., Brunetto V.L., Cella D. et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: A Gynecologic Oncology Group study. J Clin Oncol 2004; 22(11):2159−66.20. Sutton G.P., Blessing J.A., Homesley H.D. et al. Phase II study of ifosfamide and mesna in refractory adenocarcinoma of endometrium. A Gynecologic Oncology Group study. Cancer 1994;73:1453−5.Sutton G.P., Blessing J.A., Homesley H.D. et al. Phase II study of ifosfamide and mesna in refractory adenocarcinoma of endometrium. A Gynecologic Oncology Group study. Cancer 1994;73:1453−5.21. Miller D.S., Blessing J.A., Lentz S.S. et al. A phase II trial of topotecan in patients with advanced, persistent, or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Ginecol Oncol 2002;87:247−51.Miller D.S., Blessing J.A., Lentz S.S. et al. A phase II trial of topotecan in patients with advanced, persistent, or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Ginecol Oncol 2002;87:247−51.22. Al-Batran. Anthracycline-rechallenge using pegylated liposomal doxorubicin (PLD) in previously treated patients with metastatic breast cancer (MBC): A meta- analysis using pooled individual data from four prospective trials. Proc ASCO 2009, abstr.1047.Al-Batran. Anthracycline-rechallenge using pegylated liposomal doxorubicin (PLD) in previously treated patients with metastatic breast cancer (MBC): A meta- analysis using pooled individual data from four prospective trials. Proc ASCO 2009, abstr.1047.23. Muggia F.M., Blessing J.A., Sorosky J. et al. Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer: A Gynecologic Oncology Group study. J Clin Oncol 2002; 20:2360−4.Muggia F.M., Blessing J.A., Sorosky J. et al. Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer: A Gynecologic Oncology Group study. J Clin Oncol 2002; 20:2360−4.24. Fracasso P.M., Blessing J.A., Molphus K.L., et al. Phase II study of oxaliplatin as second-line chemotherapy in endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2006;103:523−6.Fracasso P.M., Blessing J.A., Molphus K.L., et al. Phase II study of oxaliplatin as second-line chemotherapy in endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2006;103:523−6.25. Garcia A.A., Blessing J.A., Nolte S. et al. A phase II evaluation of weekly docetaxel in the treatment recurrent or persistent endometrial carcinoma: A study by the Gynecologic Oncology Group. Ginecol Oncol 2008;111:22−6.Garcia A.A., Blessing J.A., Nolte S. et al. A phase II evaluation of weekly docetaxel in the treatment recurrent or persistent endometrial carcinoma: A study by the Gynecologic Oncology Group. Ginecol Oncol 2008;111:22−6.26. Lincoln S., Blessing J.A., Lee R.B. et al. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: A Gynecologic Oncology Group study by the study. Ginecol Oncol 2003;88:277−81.Lincoln S., Blessing J.A., Lee R.B. et al. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: A Gynecologic Oncology Group study by the study. Ginecol Oncol 2003;88:277−81.27. Ball H.G., Blessing J.A., Lentz S.S. et al. A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 1996;62(2): 278−81.Ball H.G., Blessing J.A., Lentz S.S. et al. A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol 1996;62(2): 278−81.28. Wartmann M., Altmann K.H. The biology and medicinal chemistry of epothilones. Curr Med Chem Anticancer Agents 2002;2:123–48.Wartmann M., Altmann K.H. The biology and medicinal chemistry of epothilones. Curr Med Chem Anticancer Agents 2002;2:123–48.29. Longley D.B., Johnston P.G. Molecular mechanisms of drug resistance. J Pathol 2005;205:275–92.Longley D.B., Johnston P.G. Molecular mechanisms of drug resistance. J Pathol 2005;205:275–92.30. Chien A.J., Moasser M.M. Cellular mechanisms of resistance to anthracyclines and taxanes in cancer: Intrinsic and acquired. Semin Oncol 2008;35 (Suppl 2):1–14.Chien A.J., Moasser M.M. Cellular mechanisms of resistance to anthracyclines and taxanes in cancer: Intrinsic and acquired. Semin Oncol 2008;35 (Suppl 2):1–14.31. Lee F.Y.F., Camuso A., Castenada S. et al. Preclinical studies of ixabepilone (BMS-247550) demonstrate optimal antitumor activity against both chemotherapy-sensitive and -resistant tumor types. Proc Am Assoc Cancer Res 2006;47:119, abstr. 503.Lee F.Y.F., Camuso A., Castenada S. et al. Preclinical studies of ixabepilone (BMS-247550) demonstrate optimal antitumor activity against both chemotherapy-sensitive and -resistant tumor types. Proc Am Assoc Cancer Res 2006;47:119, abstr. 503.32. Perez E.A., Lerzo G., Pivot X. et al. Efficacy and safety of ixabepilone (BMS- 247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol 2007;25:3407–14.Perez E.A., Lerzo G., Pivot X. et al. Efficacy and safety of ixabepilone (BMS- 247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol 2007;25:3407–14.33. Thomas E., Tabernero J., Fornier M. et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analogue, in patients with taxane-resistant metastatic breast cancer. J Clin Oncol 2007;25:3399–406.Thomas E., Tabernero J., Fornier M. et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analogue, in patients with taxane-resistant metastatic breast cancer. J Clin Oncol 2007;25:3399–406.34. Roche H., Yelle L., Cognetti F. et al. Phase II clinical trial of ixabepilone (BMS- 247550), an epothilone B analogue, as first- line therapy in patients with metastatic breast cancer previously treated with anthracycline chemotherapy. J Clin Oncol 2007;25:3415–20.Roche H., Yelle L., Cognetti F. et al. Phase II clinical trial of ixabepilone (BMS- 247550), an epothilone B analogue, as first- line therapy in patients with metastatic breast cancer previously treated with anthracycline chemotherapy. J Clin Oncol 2007;25:3415–20.35. Dizon D.S., Blessing J.A., McMeekin D.S. et al. Phase II trial of ixabepilon as second-line treatment in advanced endometrial cancer: Gynecologic Oncology Group trial 129-P. J Clin Oncol 2009;27:3104−8.Dizon D.S., Blessing J.A., McMeekin D.S. et al. Phase II trial of ixabepilon as second-line treatment in advanced endometrial cancer: Gynecologic Oncology Group trial 129-P. J Clin Oncol 2009;27:3104−8.36. Oza A.M., Elit L., Provencher D. et al. A phase II study of temsirolimus (CCI-779) in patients with metastatic and/or locally advanced recurrent endometrial cancer previously treated with chemotherapy: NCIC CTG IND 160b. J Clin Oncol 2008: 26S (Suppl), abstr. 5516.Oza A.M., Elit L., Provencher D. et al. A phase II study of temsirolimus (CCI-779) in patients with metastatic and/or locally advanced recurrent endometrial cancer previously treated with chemotherapy: NCIC CTG IND 160b. J Clin Oncol 2008: 26S (Suppl), abstr. 5516.37. Colombo N., McMeekin S., Schwartz P. et al. A phase II trial of the mTOR inhibitor AP23573 as a singl agent in advanced endometrial cancer. J Clin Oncol 2007:25 (Suppl), abstr. 5516.Colombo N., McMeekin S., Schwartz P. et al. A phase II trial of the mTOR inhibitor AP23573 as a singl agent in advanced endometrial cancer. J Clin Oncol 2007:25 (Suppl), abstr. 5516.38. Slomovitz B.M., Lu K.H., JJohnston T. et al. A phase II study of oral mammalian target of rapamycin mTOR inhibitor, RAD001 (everolimus), in patients with recurrent endometrial carcinoma. J Clin Oncol 2008;26 (Suppl), abstr. 5502.Slomovitz B.M., Lu K.H., JJohnston T. et al. A phase II study of oral mammalian target of rapamycin mTOR inhibitor, RAD001 (everolimus), in patients with recurrent endometrial carcinoma. J Clin Oncol 2008;26 (Suppl), abstr. 5502.39. Oza A.M., Poveda A., Clamp A. R. et al. A randomized phase II (RP-2) trial of ridaforolimus (R) compared with progestin (P) or chemotherapy (C) in female adult patients with advanced recurrent endometrial carcinoma. J Clin Oncol 2011;29 (suppl):334 (abstr. 5009).Oza A.M., Poveda A., Clamp A. R. et al. A randomized phase II (RP-2) trial of ridaforolimus (R) compared with progestin (P) or chemotherapy (C) in female adult patients with advanced recurrent endometrial carcinoma. J Clin Oncol 2011;29 (suppl):334 (abstr. 5009).40. Mackay H., Welch S., Tsao M. S. et al. Phase II of oral ridaforolimus in patients with metastatic and/or locally advanced recurrent endometrial cancer. J Clin Oncol 2011:29 (suppl):335 (abstr. 5013).Mackay H., Welch S., Tsao M. S. et al. Phase II of oral ridaforolimus in patients with metastatic and/or locally advanced recurrent endometrial cancer. J Clin Oncol 2011:29 (suppl):335 (abstr. 5013).41. Meyer L.A., Slomovitz B. M., Djordjevic B. et al. The search continues: Looking for predictive biomarkers for response mTOR inhibitor in endometrial cancer. J Clin Oncol 2011;29, Issue 15s (suppl):336 (abstr. 5016).Meyer L.A., Slomovitz B. M., Djordjevic B. et al. The search continues: Looking for predictive biomarkers for response mTOR inhibitor in endometrial cancer. J Clin Oncol 2011;29, Issue 15s (suppl):336 (abstr. 5016).42. Slomovitz B.M., Brown J., Johnston T. A. et al. A phase II study of everolimus with letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol 2011: 29 (suppl):335 (abstr. 5012).Slomovitz B.M., Brown J., Johnston T. A. et al. A phase II study of everolimus with letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol 2011: 29 (suppl):335 (abstr. 5012).43. Fleming G.F. Filiaci V.L, Hanjani P. et al. Hormone therapy plus temsirolimus for endometrial carcinoma. J Clin Oncol 2011;29 (suppl):335 (abstr. 5014).Fleming G.F. Filiaci V.L, Hanjani P. et al. Hormone therapy plus temsirolimus for endometrial carcinoma. J Clin Oncol 2011;29 (suppl):335 (abstr. 5014).44. Gehrig P.A., Bae-Jump V.L. Promising novel therapies for the treatment of endometrial cancer. Gynecol Oncol 2010;116:187−194.Gehrig P.A., Bae-Jump V.L. Promising novel therapies for the treatment of endometrial cancer. Gynecol Oncol 2010;116:187−194.45. Aghajanian C., Sill M.W., Darcy K.M. et al. Phase II Trial of Bevacizumab in Recurrent or Persistent Endometrial Cancer: A Gynecologic Oncology Group Study. J Clin Oncol 2011;29(16):2259−65.Aghajanian C., Sill M.W., Darcy K.M. et al. Phase II Trial of Bevacizumab in Recurrent or Persistent Endometrial Cancer: A Gynecologic Oncology Group Study. J Clin Oncol 2011;29(16):2259−65.46. Fleming G.F., Sill M.W., Darcy K.M. et al. Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2010 Jan;116(1):15−20.Fleming G.F., Sill M.W., Darcy K.M. et al. Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2010 Jan;116(1):15−20.