Treatment of uterine leiomyosarcoma
Abstract
This article is a review of uterine leiomyosarcomas treatment options. Based on the data from different trials we recommend the following treatment strategy. Surgery: total hysterectomy must be done in localized disease, further adjuvant chemotherapy is possible, but the decision should be taken individually. Adjuvant radiation therapy is not recommended due to low influence on overall survival. Advanced uterine leiomyosarcomas should be treated by combined chemotherapy. As a first line we recommend combined regimens including doxorubicin, dacarbazine, ifosfamide and gemcitabine, docetaxel. Trabectedin monotherapy as a 24-hour infusion showed good result in long-term SD and can be used as a second or further lines of treatment. Hormone therapy is possible as supportive treatment if status of steroid hormone receptors in the tumor is positive. The decision on second look surgery in advanced disease should be discussed individually. Also our data of trabectedin use in pts with uterine leiomyosarcomas is fully discussed. We got the same treatment and toxicity results as in STS-201. After the dose reduction till 1,3 mg/m2 we got more favorable toxicity profile with the same efficacy but further investigation is needed.
About the Authors
A. A. FedenkoRussian Federation
Moscow
A. A. Konev
Russian Federation
Moscow
V. A. Gorbunova
Russian Federation
Moscow
References
1. Бохман Я.В., Урманчеева А.Ф. Саркомы матки. СПб.: Гиппократ. 1996, 128 с.
2. Лазарева Н.И. Злокачественные мезенхимальные опухоли женских половых органов (клиника, диагностика, лечение, факторы прогноза). Автореферат диссертации д-ра мед. наук. М., 2003, 46 с.
3. D’angelo E., Prat J. Uterine sarcomas: a review. Gynecol Oncol. 2010, v. 116, p. 131-139.
4. Gillet D. Leiomyosarcoma of the uterus in a woman taking adjuvant tamoxifen therapy. Med. J. Aust. 1995, v. 163, p. 160Y1.
5. Cantisani V., Mortele K.J., Kalantari B.N. et al. Vaginal metastasis from uterine leiomyosarcoma. Magnetic resonance imaging features with pathological correlation. J. Comput. Assist. Tomogr. 2003, v. 27, p. 805-809.
6. Esposito N.N., Hunt J.L., Bakker A. et al. Analysis of allelic loss as an adjuvant tool in evaluation of malignancy in uterine smooth muscle tumors. Am. J. Surg. Pathol. 2006, v. 30, p. 97-103.
7. Papadimitriou C.A., Zorzou M.P, Markaki S., Rodolakis A., Voulgaris Z., Bozas G., Kastritis E., Bamias A., Gika D., Dimopoulos M.A. Anthracycline-based adjuvant chemotherapy in early-stage uterine sarcomas: long-term results of a single institution experience. Eur. J. Gynaecol Oncol. 2007, v. 28, p. 109-116.
8. Ramondetta L., Bodurka D., Deavers M., Jhingran A. Uterine Sarcomas. In M. D. Anderson Cancer Care Series, Gynecologic Cancer. Edited by Eifel P.J., Gershenson D.M., Kavanagh J.J., Silva E.G. Springer. New York. 2006, p. 125-147.
9. Gadducci A., Cosio S., Romanini A., Genazzani A.R. The management of patients with uterine sarcoma: a debated clinical challenge. Crit. Rev. Oncol. Hematol. 2008, v. 65, p. 129-142.
10. Zelmanowicz A., Hildesheim A., Sherman M.E., Sturgeon S.R, Kurman R.J., Barrett R.J., Berman M.L., Mortel R., Twiggs L.B., Wilbanks G.D., Brinton L.A. Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors. Gynecol. Oncol. 1998, v. 69, p. 253-257.
11. Giuntoli R.L. 2nd, Metzinger D.S., DiMarco C.S. et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: prognostic indicators, surgical management, and adjuvant therapy. Gynecol. Oncol. 2003, v. 89, p. 460-469.
12. Mahdavi A., Monk B.J., Ragazzo J. et al. Pelvic radiation improves local control after hysterectomy for uterine leiomyosarcoma: a 20-year experience. Int. J. Gynecol. Cancer. 2009, v. 19, p. 1080-1084.
13. Sampath S., Schultheiss T.E., Ryu J.K. et al. The role of adjuvant radiation in uterine sarcomas. Int. J. Radiat. Oncol. Biol. Phys. 2010, v. 76, p. 728-734.
14. Reed N.S., Mangioni C., Malmström H. et al. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organization for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874). Eur. J. Cancer. 2008, v. 44, p. 808-818.
15. Pervaiz N., Colterjohn N., Farrokhyar F. et al. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer. 2008, v. 113, p. 573-581.
16. Woll P.J., van Glabbeke M., Hohenberger P. et al. Adjuvant chemotherapy (CT) with doxorubicin and ifosfamide in resected soft tissue sarcoma (STS): interim analysis of a randomised phase III trial. ASCO Ann. Meet. Proc. Part I. J. Clin. Oncol. 2007, v. 25, p. 10008.
17. Italiano A, Delva F., Mathoulin-Pelissier S. et al. Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: a multivariate analysis of the French Sarcoma Group Database. Ann. Oncol. 2010, v. 12, p. 2436-2441.
18. Omura G.A., Blessing J.A., Major F. et al. A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study. J. Clin. Oncol. 1985, v. 3, p. 1240-1245.
19. Hensley M.L., Wathen K., Maki R.G. et al. 3-year followup of SaRC005: adjuvant treatment of high risk primary uterine leiomyosarcoma with gemcitabine/docetaxel, followed by doxorubicin. #78. Connective Tissue Oncology Society annual Meeting 2011, poster #78. Nov. 2011. Chicago, poster.
20. ClinicalTrials.gov Identifier: NCT01533207 (18 May 2012, date last accessed).
21. Mouridsen H.T., Bastholt L., Somers R. et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. a randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur. J. Cancer Clin. Oncol. 1987, v. 23, p. 1477-1483.
22. Nielsen O.S., Dombernowsky P., Mouridsen H. et al. Highdose 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. 1999, v. 78, p. 1634-1639.
23. Lorigan P., Verweij J., Papai Z. et al. Phase III trial of two investigational schedules of ifosfamide compared with standarddose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J. Clin. Oncol. 2007, v. 25, p. 3144-3150.
24. Bramwell V.H.C., Mouridsen H.T., Santoro A. et al. Cyclophosphamide versus ifosfamide: final report of a randomized phase II trial in adult soft tissue sarcomas. Eur. J. Cancer Clin. Oncol. 1987, v. 23, p. 311-321.
25. Verweij J., Lee S.M., Ruka W. et al. Randomized phase II study of docetaxel versus doxorubicin in first- and second-line chemotherapy for locally advanced or metastatic soft tissue sarcomas in adults: a study of the European organization for research and treatment of cancer soft tissue and bone sarcoma group. J. Clin. Oncol. 2000, v. 18, p. 2081-2086.
26. Look K.Y., Sandler A., Blessing J.A. et al. Phase II trial of gemcitabine as second-line chemotherapy of uterine leiomyosarcoma: a Gynecologic Oncology Group (GOG) Study. Gynecol. Oncol. 2004, v. 92, p. 644-647.
27. Talbot S.M., Keohan M.L., Hesdorffer M. et al. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003, v. 98, p. 1942-1946.
28. Le Cesne A., Blay J.Y., Judson I. et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J. Clin. Oncol. 2005, v. 23, p. 576-584.
29. Demetri G.D., Chawla S.P., von Mehren M. et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J. Clin. Oncol. 2009, v. 27, p. 4188-4196.
30. Sanfilippo R., Grosso F., Jones R.L. et al. Trabectedin in advanced uterine leiomyosarcomas: a retrospective case series analysis from two reference centers. Gynecol. Oncol. 2011, v. 123, p. 553-556.
31. Schöffski P., Ray-Coquard I.L., Cioffi A. et al. Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes. Lancet Oncol. 2011, v. 12, p. 1045-1052.
32. ClinicalTrials.gov Identifier: NCT01327885 (18 May 2012, date last accessed).
33. Reichardt P., Tilgner J., Hohenberger P. et al. Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study. J. Clin. Oncol. 1998, v. 16, p. 1438-1443.
34. Omura G.A., Major F.J., Blessing J.A., et al. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer. 1983, v. 52, p. 626-632.
35. Borden E.C., Amato D.A., Rosenbaum C. et al. Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J. Clin. Oncol. 1987, v. 5, p. 840-850.
36. Edmonson J.H., Ryan L.M., Blum R.H. et al. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J. Clin. Oncol. 1993, v. 11, p. 1269-1275.
37. Santoro A., Tursz T., Mouridsen H. et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J. Clin. Oncol. 1995, v. 13, p. 1537-1545.
38. Antman K., Crowley J., Balcerzak S.P. et al. An Intergroup phase III randomized study of doxorubicin and dacarbacine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J. Clin. Oncol. 1993, v. 11, p. 1276-1285.
39. Judson I., Verwei J., Gelderblom H. et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Mar 4. pii: S1470-2045(14)70063-4.
40. Hensley M.L., Maki R., Venkatraman E. et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J. Clin. Oncol. 2002, v. 20, p. 2824-2831.
41. Hensley M.L., Blessing J.A., Degeest K. et al. Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study. Gynecol. Oncol. 2008, v. 109, p. 323-328.
42. Hensley M.L., Blessing J.A., Mannel R. et al. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 2008, v. 109, p. 329-334.
43. Maki R.G., Wathen J.K., Patel S.R. et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002. J. Clin. Oncol. 2007, v. 25, p. 2755-2763.
44. ClinicalTrials.gov Identifier: NCT00189137 (18 May 2012, date last accessed).
45. O’Cearbhaill R., Zhou Q., Iasonos A. et al. Treatment of advanced uterine leiomyosarcoma with aromatase inhibitors. Gynecol Oncol. 2010, v. 116, p. 424-429.
46. Hensley M.L., Sill M.W., Scribner D.R. Jr. et al. Sunitinib malate in the treatment of recurrent or persistent uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study. Gynecol. Oncol. 2009, v. 115, p. 460-465.
47. Maki R.G., D’Adamo D.R., Keohan M.L. et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J. Clin. Oncol. 2009, v. 27, p. 3133-3140.
48. Sleijfer S., Ray-Coquard I., Papai Z. et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study62043). J. Clin. Oncol. 2009, v. 27, p. 3126-3132.
49. Van der Graaf W.T., Blay J.Y., Chawla S.P. et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012, v. 379, p. 1879-1886.
50. Chawla S.P., Blay J., Ray-Coquard I.L. et al. Results of the phase III, placebo-controlled trial (SUCCEED) evaluating the mTOR inhibitor ridaforolimus (R) as maintenance therapy in advanced sarcoma patients (pts) following clinical benefit from prior standard cytotoxic chemotherapy (CT). J. Clin. Oncol. 2011, v. 29 (Suppl.) (abstr 10005).
51. Verschraegen C.F., Arias-Pulido H., Lee S.J. et al. Phase IB study of the combination of docetaxel, gemcitabine, and bevacizumab in patients with advanced or recurrent soft tissue sarcoma: the axtell regimen. Ann. Oncol. 2012, v. 23, p. 785-790.
52. ClinicalTrials.gov Identifier: NCT01012297 (18 May 2012, date last accessed).
Review
For citations:
Fedenko A.A., Konev A.A., Gorbunova V.A. Treatment of uterine leiomyosarcoma. Bone and soft tissue sarcomas, tumors of the skin. 2014;(1):56-63. (In Russ.)