Bone and soft tissue sarcomas, tumors of the skinBone and soft tissue sarcomas, tumors of the skinСаркомы костей, мягких тканей и опухоли кожи2219-46142782-3687Publishing House ABV Press212ArticlesСтатьиTrabectedin in the treatment of soft tissue sarcomas. First russian experienceПЕРВЫЙ РОССИЙСКИЙ ОПЫТ ПРИМЕНЕНИЯ ТРАБЕКТЕДИНА В ЛЕЧЕНИИ ДИССЕМИНИРОВАННЫХ САРКОМ МЯГКИХ ТКАНЕЙFedenkoA. A.ФеденкоА. А.
Russian Federation
fedenko@eesg.ruGorbunovaV. A.ГорбуноваВ. А.
Russian Federation
BokhyanB. Yu.БохянБ. Ю.
Russian Federation
AlievM. D.АлиевМ. Д.
Russian Federation
IstominI. A.ИстоминИ. А.
Russian Federation
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical SciencesРоссийский онкологический научный центр им. Н.Н. Блохина РАМН1104201132475411012022Copyright ©; 2011, Fedenko A.A., Gorbunova V.A., Bokhyan B.Y., Aliev M.D., Istomin I.A.Copyright ©; 2011, Феденко А.А., Горбунова В.А., Бохян Б.Ю., Алиев М.Д., Истомин И.А.2011Fedenko A.A., Gorbunova V.A., Bokhyan B.Y., Aliev M.D., Istomin I.A.Феденко А.А., Горбунова В.А., Бохян Б.Ю., Алиев М.Д., Истомин И.А.https://creativecommons.org/licenses/by/4.0https://sarbon.abvpress.ru/jour/article/view/212

Aim of the study was to evaluate efficacy and safety of 24-hour 3 weekly CI infusion of trabectedine in patients with specific soft tissue sarcomas subtypes as a second or more treatment option. Materials and methods. 21 patients with PD after one or more lines of chemotherapy were enrolled. 12 pts. with leiomyo, 7 -synovial and 3 myxoid liposarcoma. Detailed toxicity profile evaluation was performed and the obtained data almost equals STS 201 trial. Patients received 2-9 cycles with median 4 cycles. Results. 20 patients were available for the response assessment: CR - 0, PR - 3 (15%), SD - 11 (55%), PD - 6 (30%) with the control rate (CR+PR+SD) of 70%. Conclusion. Trabectedine is effective second or more line treatment option for advanced specific STS subtypes with acceptable toxicity profile.

Цель исследования. Изучить эффективность и переносимость монотерапии трабектедином по 1,5 мг/м2 в виде суточной инфузии раз в 21 день у больных диссеминированными саркомами мягких тканей (СМТ) после одной или более линий ПХТ. Материалы и методы. В исследование включен 21 пациент с СМТ при прогрессировании после 1 и более линий ПХТ - 12 больных с лейомиосаркомой, 7 - с синовиальной и 3 - с миксоидной липосаркомой. Проведен подробный анализ профиля токсичности, при этом полученные данные практически не отличаются от результатов исследования STS 201. Было проведено от 2 до 9 курсов терапии, в среднем 4. Результаты. У 20 больных проведена оценка эффективности: CR - 0 больных, PR - 3 (15%); SD - 11 (55 %); PD - 6 (30%). контроль роста опухоли составил 70%. Заключение. трабектедин в монотерапии является высокоэффективным препаратом для лечения отдельных гистологических подтипов диссеминированных СМТс приемлемым профилем токсичности.

soft tissue sarcomatrabectedinemorphological subtypessensitivityсаркома мягких тканейтрабектединморфологические подтипыCoindre J.M., Terrier P., Guillou L. et al. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer. 2001, v. 91, p. 1914-1926.Pervaiz N., Colterjohn N., Farrokhyar F. et al. A systematic meta-analysis of randomized controlled trials for adjuvant chemotherapy for localized resectable soft tissue sarcoma. Cancer. 2008, v. 113 (3), p. 573-581.Ferrari A., Gronchi A., Casanova M. et al. Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer. 2004, v. 101 (3), p. 627-634.Eilber F.C., Eilber F.R., Eckardt J. et al. The impact of chemotherapy on the survival of patients with high-grade primary extremity liposarcoma. Ann. Surg. 2004, v. 240 (4), p. 686-695.Nielsen O.S., Dombernowsky P., Mouridsen H. et al. High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas: a study of the EORTC Soft Tissue and Bone Sarcoma Group. Br. J. Cancer. 1998, v. 78, p. 1634-1639.Le Cesne A., Judson I., Crowther D. et al. Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: A trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J. Clin. Oncol. 2000, v. 18, p. 2676-2684.Bokemcyer C., Franzke A., Hartmann J.T. еt al. A Phase 1/11 study of sequential, dose-escalated high-dose ifosfamide plus doxorubicin with peripheral blood stem cell support, for the treatment of patients with advanced soft tissue sarcomas. Cancer. 1997, v. 80, p. 1221-1227.Patel S.R., Vadhan-Raj S., Burgess M.A. et al. Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am. J. Clin. Oncol. 1998, v. 21, p. 317-321.Brennan M.F., Casper E.S., Harrison L.B. Soft tissue sarcoma. En: De Vita V.T, Hellman S., Rosemberg S.A., eds. Cancer: Principles and Practice of Oncology. Philadelphia: Lippincott- Raven. 1997, p. 1738-1788.Van Glabbeke M., Verwcij J., Judson I. et al. Progression-free rate as the principal end point for Phase 11 trials in soft tissue sarcomas. Eur. J. Cancer. 2002, v. 38, p. 543-549.Roland T., Skeel. Handbook of Cancer Chemotherapy. 2003.Choi. H., Charnsangavej C., Faria S.C. et al. Correlation of Computed Tomography and Positron Emission Tomography in Patients With Metastatic Gastrointestinal Stromal Tumor Treated at a Single Institution With Imatinib Mesylate: Proposal of New Computed Tomography Response CriteriaASCO 2007 Journal of Clinical Oncology, v. 25, No. 13 (May 1), 2007, p. 1753-1759. DOI: 10.1200/JCO.2006.07.3049.Van Glabbeke, van Oosterom A.T, Oosterhuis J.W et al. Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with antracycline-containing first line regimens - a European Organization for Research and Treatment of Cancer Soft-Tissue and Bone Sarcoma Group Study. Clin. Oncol. 1999, v. 17, p. 150-157.Pommier Y, Kohlhagen G., Bailly C. et al. DNA sequence-and structureselective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the carribean tunicate Ecteinascidia Turbinata. Biochemistry. 1996, v. 35, p. 13303-13309.Schoffski P., Wolter P., Clement P. et al. Trabectidin (ET-743): evaluation of its use in advanced soft tissue sarcoma. Future Oncol. 2007, v. 3 (4), p. 381-392.Garcia-Carbonero R., Supko J.G., Manola J. et al. Phase II and pharmacokinetic studyof ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy J. Clin. Oncol. 2004, v. 22, p. 1480-1490.Le Cesne A., Blay J .Y, Judson I. et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organization for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. Clin. Oncol. 2005, v. 23, p. 576-584.Yovine A., Riofrio M., Blay J.Y et al. Phase II study of actenas-cidin-743 in advanced pretreated soft tissue sarcoma patients. J. Clin. Oncol. 2004, v. 22, p. 890-899.George D. Demetri, Sant P. Chawla, M. von Mehren et al. Efficacy and safety of trabectidin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after anthracycines and ifosfamide: results of a randomized phase II study of two different schedules. J. Clin. Oncol. 2009, v. 27, ASCO, p. 1-19.Garcia-Carbonero R., Supko J.G., Maki R.G. et al. Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter Phase II and pharmacokinetic study. Clin. Oncol. 2005, v. 23, p. 5484-5492.Schoffski P. DNA repair functionality as a molecular signature for sensitivity/resistance in sarcoma patients treated with trabectedin. Presented at: 43rd ASCO Annual Meeting. Los Angeles, CA, USA. 2007, April 14-18.Grosso F., Demetri G., Blay J.Y. et al. Patterns of tumor response to trabectedin in myxoid liposarcomas. Program and Abstracts of the 42nd ASCO Annual Meeting. Atlanta, GA, USA, 2-6 June (2006). Clin. Oncol. 24 (18S) (2006) 52. (Abstract 9511).Walker S., Norwood J., Thornton C., Schaberg D. Trimethoprim-sulfamethoxazole associated rhabdomyolysis in a patient with AIDS: Case report and review of the literature. The American Journal of the Medical Sciences. 2006, v. 331, p. 33941.Levy R.J., Sparano J.A., Khan G. Rhabdomyolysis: An unusual complication of cytotoxic chemotherapy. Medical Oncology (Northwood, London, England). 1995, v. 12, p. 219-222.Koeffler H.P., Haskell C.M. Rhabdomyolysis as a complication of 5-azacytidine. Cancer. Treatment Reports. 1978, v. 62, p. 573-574.Reinhold U., Hartl C., Hering R. et al. Fatal rhabdomyolysis and multiple organ failure associated with adjuvant high-dose interferon alfa in malignant melanoma. Lancet. 1997, v. 349, p. 540-541.Ceribelli A., Cecere F.L., Milella M. et al. Severe rhabdomyolysis associated with pemetrexed based chemotherapy. The Lancet. Oncology. 2006, v. 7, p. 353.Truica C.I., Frankel S.R. Acute rhabdomyolysis as a complication of cytarabine chemotherapy for acute myeloid leukemia: Case report and review of literature. American Journal of Hematology. 2002, v. 70, p. 320-323.Cibeira M.T, Mercadal S., Arenillas L. et al. Bortezomib induced rhabdomyolysis in multiple myeloma. Acta Haematologica. 2006, v. 116, p. 203-206.