Optimal management of uterine leiomyosarcoma

Expert Review of Anticancer Therapy

Volumn 10, Issue 2, 2010, Pages 153-169

  O'Cearbhaill, Roisin ^a   Hensley, Martee L ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Anti angiogenics; Chemotherapy; Hormone therapy; Metastectomy; Radiotherapy; Sarcoma; Staging system; Surgical resection; Thermal ablation; Uterine leiomyosarcoma

Indexed keywords

AMINOTHIADIAZOLE; AMONAFIDE; ANTHRACYCLINE; BEVACIZUMAB; CISPLATIN; CYCLOPHOSPHAMIDE; DACARBAZINE; DIAZIQUONE; DOCETAXEL; DOXORUBICIN; ETOPOSIDE; GEMCITABINE; GRANULOCYTE COLONY STIMULATING FACTOR; HYDROXYUREA; IFOSFAMIDE; MEDROXYPROGESTERONE ACETATE; MESNA; MITOMYCIN; MITOXANTRONE; NAVELBINE; PACLITAXEL; SORAFENIB; SUNITINIB; TEMOZOLOMIDE; THALIDOMIDE; TOPOTECAN; TRABECTEDIN; TRIMETREXATE; UNINDEXED DRUG; VINCRISTINE;

ABDOMINAL HYSTERECTOMY; ABDOMINAL PAIN; ADJUVANT THERAPY; ADVANCED CANCER; ANEMIA; ANOREXIA; ASTHENIA; BLADDER DISEASE; BONE MARROW SUPPRESSION; BONE MARROW TOXICITY; BRACHYTHERAPY; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER EPIDEMIOLOGY; CANCER HORMONE THERAPY; CANCER MORTALITY; CANCER PALLIATIVE THERAPY; CANCER RADIOTHERAPY; CANCER RECURRENCE; CANCER STAGING; CANCER SURGERY; CANCER SURVIVAL; CARCINOSARCOMA; CLINICAL TRIAL; CONTINUOUS INFUSION; CRYOABLATION; DIARRHEA; DISEASE FREE SURVIVAL; DRUG EFFICACY; DRUG ERUPTION; DRUG HYPERSENSITIVITY; DRUG INDUCED DISEASE; DRUG MEGADOSE; DRUG POTENTIATION; DRUG WITHDRAWAL; DYSPNEA; ENTEROPATHY; EXTERNAL BEAM RADIOTHERAPY; FATIGUE; FEBRILE NEUTROPENIA; FOOT EDEMA; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL TOXICITY; HAND FOOT SYNDROME; HEART EJECTION FRACTION; HUMAN; HYPERTRANSAMINASEMIA; INTESTINE PERFORATION; LEIOMYOSARCOMA; LIPOSARCOMA; LIVER TOXICITY; LUNG TOXICITY; LYMPHADENECTOMY; METASTASIS; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MYALGIA; MYOMECTOMY; NAUSEA; NEUROTOXICITY; NEUTROPENIA; OVERALL SURVIVAL; PARESTHESIA; PNEUMOTHORAX; RADIATION INJURY; RADIOFREQUENCY ABLATION; RECURRENT CANCER; REVIEW; SALPINGOOOPHORECTOMY; SIDE EFFECT; SKIN TOXICITY; SOFT TISSUE SARCOMA; THROMBOCYTOPENIA; TREATMENT OUTCOME; UTERUS LEIOMYOSARCOMA; UTERUS SARCOMA; VAGINA BLEEDING; VOMITING;

CLINICAL TRIALS AS TOPIC; COMBINED MODALITY THERAPY; FEMALE; HUMANS; LEIOMYOSARCOMA; RECURRENCE; UTERINE NEOPLASMS;

EID: 76749109940     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/ERA.09.187     Document Type: Review

References (121)

1. Echt G, Jepson J, Steel J et al. Treatment of uterine sarcomas. Cancer 66(1), 35-39 (1990).
2. Toro JR, Travis LB, Wu HJ, Zhu K, Fletcher CD, Devesa SS. Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: an analysis of 26,758 cases. Int. J. Cancer 119(12), 2922-2930 (2006).
3. Major FJ, Blessing JA, Silverberg SG et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer 71(4 Suppl.), 1702-1709 (1993).
4. Giuntoli RL 2nd, Metzinger DS, DiMarco CS et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: prognostic indicators, surgical management, and adjuvant therapy. Gynecol. Oncol. 89(3), 460-469 (2003).
5. Kapp DS, Shin JY, Chan JK. Prognostic factors and survival in 1396 patients with uterine leiomyosarcomas: emphasis on impact of lymphadenectomy and oophorectomy. Cancer 112(4), 820-830 (2008). • Largest retrospective review evaluating the role of lymphadenectomy and oophorectomy in uterine leiomyosarcoma, suggesting that both may not be required when disease appears to be confined to the uterus.
6. Zivanovic O, Leitao MM, Iasonos A et al. Stage-specific outcomes of patients with uterine leiomyosarcoma: a comparison of the International Federation of Gynecology and Obstetrics and American Joint Committee on Cancer Staging Systems. J. Clin. Oncol. 27(12), 2066-2072 (2009).
7. Raut CP, Nucci MR, Wang Q et al. Predictive value of FIGO and AJCC staging systems in patients with uterine leiomyosarcoma. Eur. J. Cancer 45(16), 2818-2824 (2009).
8. Hensley ML, Ishill N, Soslow R et al. Adjuvant gemcitabine plus docetaxel for completely resected stages I-IV high grade uterine leiomyosarcoma: results of a prospective study. Gynecol. Oncol. 112(3), 563-567 (2009). •• Phase II study of adjuvant gemcitabine plus docetaxel in patients with completely resected uterine leiomyosarcoma. Disease-free and overall survival appeared to be improved with adjuvant chemotherapy when compared with historical data of observation alone.
9. Prat J. FIGO staging for uterine sarcomas. Int. J. Gynaecol. Obstet. 104(3), 177-179 (2009).
10. Einstein MH, Barakat RR, Chi DS et al. Management of uterine malignancy found incidentally after supracervical hysterectomy or uterine morcellation for presumed benign disease. Int. J. Gynecol. Cancer 18(5), 1065-1070 (2008).
11. Lissoni A, Cormio G, Bonazzi C et al. Fertility-sparing surgery in uterine leiomyosarcoma. Gynecol. Oncol. 70(3), 348-350 (1998).
12. Cormio G, Loizzi V, Carriero C, Scardigno D, Putignano G, Selvaggi L. Conservative management of uterine leiomyosarcoma: report of a failure. Eur. J. Gynaecol. Oncol. 30(2), 206-207 (2009).
13. Leitao MM, Sonoda Y, Brennan MF, Barakat RR, Chi DS. Incidence of lymph node and ovarian metastases in leiomyosarcoma of the uterus. Gynecol. Oncol. 91(1), 209-212 (2003).
14. Leitao MM, Soslow RA, Nonaka D et al. Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma. Cancer 101(6), 1455-1462 (2004).
15. Goff BA, Rice LW, Fleischhacker D et al. Uterine leiomyosarcoma and endometrial stromal sarcoma: lymph node metastases and sites of recurrence. Gynecol. Oncol. 50(1), 105-109 (1993).
16. Parker WH, Fu YS, Berek JS. Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma. Obstet. Gynecol. 83(3), 414-418 (1994).
17. Leibsohn S, d'Ablaing G, Mishell DR Jr, Schlaerth JB. Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas. Am. J. Obstet. Gynecol. 162(4), 968-974 (1990).
18. Goldberg J, Burd I, Price FV, Worthington-Kirsch R. Leiomyosarcoma in a premenopausal patient after uterine artery embolization. Am. J. Obstet. Gynecol. 191(5), 1733-1735 (2004).
19. Posy HES, Elkas JC, Yemelyanova AV, Diaz-Montes TP, Bristow RE, Giuntoli RL. Metastatic leiomyosarcoma diagnosed after uterine artery embolization. Eur. J. Gynaecol. Oncol. 30(2), 199-202 (2009).
20. Sorbe B, Johansson B. Prophylactic pelvic irradiation as part of primary therapy in uterine sarcomas. Int. J. Oncol. 32(5), 1111-1117 (2008).
21. Hornback NB, Omura G, Major FJ. Observations on the use of adjuvant radiation therapy in patients with stage I and II uterine sarcoma. Int. J. Radiat. Oncol. Biol. Phys. 12(12), 2127-2130 (1986).
22. Sampath S, Schultheiss TE, Ryu JK, Wong JY. The role of adjuvant radiation in uterine sarcomas. Int. J. Radiat. Oncol. Biol. Phys. (2009) (Epub ahead of print).
23. Reed NS, 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 Organisation for Research and Treatment of Cancer Gynaecological Cancer Group study (protocol 55874). Eur. J. Cancer 44(6), 808-818 (2008). •• Large prospective trial of adjuvant radiotherapy in patients with resected early-stage uterine sarcoma. In the leiomyosarcoma patients, postoperative radiotherapy did not significantly improve disease-free or overall survival.
24. Leyvraz S, Zweifel M, Jundt G et al. Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas. Ann. Oncol. 17(4), 646-651 (2006).
25. Pervaiz N, Colterjohn N, Farrokhyar F, Tozer R, Figueredo A, Ghert M. A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma. Cancer 113(3), 573-581 (2008).
26. Omura G, Blessing J, Major F et al. A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group study. J. Clin. Oncol. 3(9), 1240-1245 (1985).
27. Pautier P, Rey A, Haie-Meder C et al. Adjuvant chemotherapy with cisplatin, ifosfamide, and doxorubicin followed by radiotherapy in localized uterine sarcomas: results of a case-control study with radiotherapy alone. Int. J. Gynecol. Cancer 14(6), 1112-1117 (2004).
28. Hempling RE, Piver MS, Baker TR. Impact on progression-free survival of adjuvant cyclophosphamide, vincristine, doxorubicin (adriamycin), and dacarbazine (CYVADIC) chemotherapy for stage I uterine sarcoma. A prospective trial. Am. J. Clin. Oncol. 18(4), 282-286 (1995).
29. Hensley ML, Anderson S, Soslow R et al. Activity of gemcitabine plus docetaxel in leiomyosarcoma (LMS) and other histologies: report of an expanded Phase II trial. J. Clin. Oncol. (Meeting Abstracts) 22(14 Suppl.), (2004) (Abstract 9010).
30. Hensley ML, Blessing JA, Degeest K, Abulafia O, Rose PG, Homesley HD. Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group Phase II study. Gynecol. Oncol. 109(3), 323-328 (2008).
31. Hensley ML, Blessing JA, Mannel R, Rose PG. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group Phase II trial. Gynecol. Oncol. 109(3), 329-334 (2008). •• Phase II study of gemcitabine plus docetaxel showing objective response rate of 36% in chemotherapy-naive patients with metastatic uterine leiomyosarcoma. Disease-free and overall surival appeared to be improved with adjuvant chemotherapy when compared with historical data of observation alone.
32. Leu KM, Ostruszka LJ, Shewach D et al. Laboratory and clinical evidence of synergistic cytotoxicity of sequential treatment with gemcitabine followed by docetaxel in the treatment of sarcoma. J. Clin. Oncol. 22(9), 1706-1712 (2004).
33. Kanjeekal S, Chambers A, Fung MF, Verma S. Systemic therapy for advanced uterine sarcoma: a systematic review of the literature. Gynecol. Oncol. 97(2), 624-637 (2005).
34. Asbury R, Blessing JA, Smith DM, Carson LF. Aminothiadiazole in the treatment of advanced leiomyosarcoma of the uterine corpus. A Gynecologic Oncology Group study. Am. J. Clin. Oncol. 18(5), 397-399 (1995).
35. Asbury R, Blessing JA, Buller R, Malfetano JH, Walker J, Sevin BU. Amonafide in patients with leiomyosarcoma of the uterus: a Phase II Gynecologic Oncology Group study. Am. J. Clin. Oncol. 21(2), 145-146 (1998).
36. Thigpen JT, Blessing JA, Beecham J, Homesley H, Yordan E. Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. J. Clin. Oncol. 9(11), 1962-1966 (1991).
37. Slayton RE, Blessing JA, Look K, Anderson B. A Phase II clinical trial of diaziquone (AZQ) in the treatment of patients with recurrent leiomyosarcoma of the uterus. A Gynecologic Oncology Group study. Invest. New Drugs 9(2), 207-208 (1991).
38. Verweij J, Lee SM, 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. 18(10), 2081-2086 (2000).
39. Rose PG, Blessing JA, Soper JT, Barter JF. Prolonged oral etoposide in recurrent or advanced leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol. Oncol. 70(2), 267-271 (1998).
40. Muss HB, Bundy BN, Adcock L, Beecham J. Mitoxantrone in the treatment of advanced uterine sarcoma. A Phase II trial of the Gynecologic Oncology Group. Am. J. Clin. Oncol. 13(1), 32-34 (1990).
41. Gallup DG, Blessing JA, Andersen W, Morgan MA. Evaluation of paclitaxel in previously treated leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol. Oncol. 89(1), 48-51 (2003).
42. Sutton G, Blessing JA, Ball H. Phase II trial of paclitaxel in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol. Oncol. 74(3), 346-349 (1999).
43. McMeekin DS, Sill MW, Darcy KM et al. A Phase II trial of thalidomide in patients with refractory leiomyosarcoma of the uterus and correlation with biomarkers of angiogenesis: a Gynecologic Oncology Group study. Gynecol. Oncol. 106(3), 596-603 (2007).
44. Smith HO, Blessing JA, Vaccarello L. Trimetrexate in the treatment of recurrent or advanced leiomyosarcoma of the uterus: a Phase II study of the Gynecologic Oncology Group. Gynecol. Oncol. 84(1), 140-144 (2002).
45. Slayton RE, Blessing JA, Angel C, Berman M. Phase II trial of etoposide in the management of advanced and recurrent leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Cancer Treat. Rep. 71(12), 1303-1304 (1987).
46. Thigpen T, Blessing JA, Yordan E, Valea F, Vaccarello L. Phase II trial of etoposide in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol. Oncol. 63(1), 120-122 (1996).
47. Fidias P, Demetri G, Harmon D. Navelbine shows activity in previously treated sarcoma patients: Phase II results from MGH/Dana Farber/Partner's Cancercare study. Proc. Am. Soc. Clin. Oncol. (1998) (Abstract 1977).
48. Anderson SE, Keohan ML, D'Adamo DR, Maki RG. A retrospective analysis of vinorelbine chemotherapy for patients with previously treated soft-tissue sarcomas. Sarcoma 2006, 15947 (2006).
49. Miller DS, Blessing JA, Kilgore LC, Mannel R, Van Le L. Phase II trial of topotecan in patients with advanced, persistent, or recurrent uterine leiomyosarcomas: a Gynecologic Oncology Group study. Am. J. Clin. Oncol. 23(4), 355-357 (2000).
50. Omura GA, Major FJ, Blessing JA et al. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer 52(4), 626-632 (1983). •• Phase III trial demonstrating an objective response rate of 25% with single-agent doxorucibicin in patients with advanced uterine leiomyosarcoma.
51. Sutton GP, Blessing JA, Barrett RJ, McGehee R. Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Am. J. Obstet. Gynecol. 166(2), 556-559 (1992).
52. Look KY, Sandler A, Blessing JA, Lucci JA 3rd, Rose PG. Phase II trial of gemcitabine as second-line chemotherapy of uterine leiomyosarcoma: a Gynecologic Oncology Group (GOG) study. Gynecol. Oncol. 92(2), 644-647 (2004).
53. Anderson S, Aghajanian C. Temozolomide in uterine leiomyosarcomas. Gynecol. Oncol. 98(1), 99-103 (2005).
54. Talbot SM, Keohan ML, Hesdorffer M et al. A Phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer 98(9), 1942-1946 (2003).
55. Garcia-Carbonero R, Supko JG, Maki RG et al. Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter Phase II and pharmacokinetic study. J. Clin. Oncol. 23(24), 5484-5492 (2005).
56. Grosso F, Sanfilippo R, Jones RL et al. Role of trabectedin (T) in the management of advanced uterine leiomyosarcoma (U-LM). J. Clin. Oncol. 27(15S), (2009) (Abstract 10530).
57. Sutton G, Blessing J, Hanjani P, Kramer P. Phase II evaluation of liposomal doxorubicin (Doxil) in recurrent or advanced leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol. Oncol. 96(3), 749-752 (2005).
58. Lorigan P, Verweij J, Papai Z et al. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose 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. 25(21), 3144-3150 (2007).
59. Hensley ML, Hagerty KL, Kewalramani T et al. American Society of Clinical Oncology 2008 Clinical Practice Guideline Update: use of chemotherapy and radiation therapy protectants. J. Clin. Oncol. 27(1), 127-145 (2009).
60. Dileo P, Morgan J, Zahrieh D et al. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a Phase II trial. Cancer 109(9), 1863-1869 (2007).
61. Minuzzo M, Marchini S, Broggini M, Faircloth G, D'Incalci M, Mantovani R. Interference of transcriptional activation by the antineoplastic drug ecteinascidin-743. Proc. Natl Acad. Sci. USA 97(12), 6780-6784 (2000).
62. Jin S, Gorfajn B, Faircloth G, Scotto KW. Ecteinascidin 743, a transcription-targeted chemotherapeutic that inhibits MDR1 activation. Proc. Natl Acad. Sci. USA 97(12), 6775-6779 (2000).
63. Garcia-Carbonero R, Supko JG, Manola J et al. Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J. Clin. Oncol. 22(8), 1480-1490 (2004).
64. Yovine A, Riofrio M, Blay JY et al. Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. J. Clin. Oncol. 22(5), 890-899 (2004).
65. Le Cesne A, Blay JY, 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. 23(3), 576-584 (2005).
66. Beumer JH, Schellens JHM, Beijnen JH. Hepatotoxicity and metabolism of trabectedin: a literature review. Pharmacol. Res. 51(5), 391-398 (2005).
67. Cioffi A, LeCesne A, Blay J et al. Trabectedin Phase II clinical trials: pooled analysis of safety in patients with solid tumors. J. Clin. Oncol. 27(15S), (2009) (Abstract e13510).
68. Demetri GD, Chawla SP, 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. 27(25), 4188-4196 (2009).
69. Muss HB, Bundy B, DiSaia PJ et al. Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a Phase III trial of the Gynecologic Oncology Group). Cancer 55(8), 1648-1653 (1985).
70. Currie J, Blessing JA, Muss HB, Fowler J, Berman M, Burke TW. Combination chemotherapy with hydroxyurea, dacarbazine (DTIC), and etoposide in the treatment of uterine leiomyosarcoma: a Gynecologic Oncology Group study. Gynecol. Oncol. 61(1), 27-30 (1996).
71. Edmonson JH, Blessing JA, Cosin JA, Miller DS, Cohn DE, Rotmensch J. Phase II study of mitomycin, doxorubicin, and cisplatin in the treatment of advanced uterine leiomyosarcoma: a Gynecologic Oncology Group study. Gynecol. Oncol. 85(3), 507-510 (2002).
72. Sutton G, Blessing JA, Malfetano JH. Ifosfamide and doxorubicin in the treatment of advanced leiomyosarcomas of the uterus: a Gynecologic Oncology Group study. Gynecol. Oncol. 62(2), 226-229 (1996). • Phase II study of ifosfamide and doxorubicin showing objective response rate of 30% in uterine leiomyosarcoma.
73. Maurel J, Lopez-Pousa A, de Las Penas R et al. Efficacy of sequential high-dose doxorubicin and ifosfamide compared with standard-dose doxorubicin in patients with advanced soft tissue sarcoma: an open-label randomized Phase II study of the Spanish group for research on sarcomas. J. Clin. Oncol. 27(11), 1893-1898 (2009). •• Phase II study showing no advantage to adding sequential ifosfamide to doxorubicin compared with doxorubicin alone.
74. Patel SR, Gandhi V, Jenkins J et al. Phase II clinical investigation of gemcitabine in advanced soft tissue sarcomas and window evaluation of dose rate on gemcitabine triphosphate accumulation. J. Clin. Oncol. 19(15), 3483-3489 (2001).
75. Grunewald R, Abbruzzese JL, Tarassoff P, Plunkett W. Saturation of 2′,2′-difluorodeoxycytidine 5′-triphosphate accumulation by mononuclear cells during a Phase I trial of gemcitabine. Cancer Chemother. Pharmacol. 27(4), 258-262 (1991).
76. Bay JO, Ray-Coquard I, Fayette J et al. Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcomas: a retrospective analysis. Int. J. Cancer 119(3), 706-711 (2006).
77. Maki RG, Wathen JK, Patel SR 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. 25(19), 2755-2763 (2007).
78. Leitao MM, Brennan MF, Hensley M et al. Surgical resection of pulmonary and extrapulmonary recurrences of uterine leiomyosarcoma. Gynecol. Oncol. 87(3), 287-294 (2002).
79. Weiser MR, Downey RJ, Leung DH, Brennan MF. Repeat resection of pulmonary metastases in patients with soft-tissue sarcoma. J. Am. Coll. Surg. 191(2), 184-190 (2000).
80. Nguyen CL, Scott WJ, Goldberg M. Radiofrequency ablation of lung malignancies. Ann. Thorac. Surg. 82(1), 365-371 (2006).
81. Herrera LJ, Fernando HC, Perry Y et al. Radiofrequency ablation of pulmonary malignant tumors in nonsurgical candidates. J. Thorac. Cardiovasc. Surg. 125(4), 929-937 (2003).
82. Nakamura T, Matsumine A, Yamakado K et al. Lung radiofrequency ablation in patients with pulmonary metastases from musculoskeletal sarcomas. Cancer 115(16), 3774-3781 (2009). • First case series of patients with soft-tissue sarcomas who underwent radiofrequency ablation for lung metastases.
83. O'Cearbhaill R, Maki R, Zheng J et al. Evaluation of the role of thermal ablation in the treatment of soft tissue sarcomas. In: Connective Tissue Oncology Society Annual Meeting. Miami Beach, FL, USA (2009).
84. Spanos WJ Jr, Perez CA, Marcus S et al. Effect of rest interval on tumor and normal tissue response - a report of Phase III study of accelerated split course palliative radiation for advanced pelvic malignancies (RTOG-8502). Int. J. Radiat. Oncol. Biol. Phys. 25(3), 399-403 (1993).
85. Spanos WJ Jr, Wasserman T, Meoz R, Sala J, Kong J, Stetz J. Palliation of advanced pelvic malignant disease with large fraction pelvic radiation and misonidazole: final report of RTOG Phase I/II study. Int. J. Radiat. Oncol. Biol. Phys. 13(10), 1479-1482 (1987).
86. Akhan SE, Yavuz E, Tecer A et al. The expression of Ki-67, p53, estrogen and progesterone receptors affecting survival in uterine leiomyosarcomas. A clinicopathologic study. Gynecol. Oncol. 99(1), 36-42 (2005).
87. Rao UN, Finkelstein SD, Jones MW. Comparative immunohistochemical and molecular analysis of uterine and extrauterine leiomyosarcomas. Mod. Pathol. 12(11), 1001-1009 (1999).
88. Soper JT, McCarty KS Jr, Hinshaw W, Creasman WT, McCarty KS Sr, Clarke-Pearson DL. Cytoplasmic estrogen and progesterone receptor content of uterine sarcomas. Am. J. Obstet. Gynecol. 150(4), 342-348 (1984).
89. Zhai YL, Kobayashi Y, Mori A et al. Expression of steroid receptors, Ki-67, and p53 in uterine leiomyosarcomas. Int. J. Gynecol. Pathol. 18(1), 20-28 (1999).
90. Uchida T, Nakakawaji K, Sakamoto J et al. The effectiveness of medroxyprogesterone in the treatment of multiple metastasizing leiomyosarcomas: report of a case. Surg. Today 26(2), 138-141 (1996).
91. Wade K, Quinn MA, Hammond I, Williams K, Cauchi M. Uterine sarcoma: steroid receptors and response to hormonal therapy. Gynecol. Oncol. 39(3), 364-367 (1990).
92. Lavie O, Barnett-Griness O, Narod SA, Rennert G. The risk of developing uterine sarcoma after tamoxifen use. Int. J. Gynecol. Cancer 18(2), 352-356 (2008).
93. O'Cearbhaill R, Zhou Q, Iasonos A et al. Evaluation of the role of aromatase inhibitors (AIs) in the treatment of uterine leiomyosarcoma (uLMS). J. Clin. Oncol. 27(15S), (2009). • Largest case series of uterine leiomyosarcoma patients treated with an aromatase inhibitor, suggesting that patients with hormone receptor-negative tumors do not benefit.
94. Chao C, Al-Saleem T, Brooks JJ, Rogatko A, Kraybill WG, Eisenberg B. Vascular endothelial growth factor and soft tissue sarcomas: tumor expression correlates with grade. Ann. Surg. Oncol. 8(3), 260-267 (2001).
95. Graeven U, Andre N, Achilles E, Zornig C, Schmiegel W. Serum levels of vascular endothelial growth factor and basic fibroblast growth factor in patients with soft-tissue sarcoma. J. Cancer Res. Clin. Oncol. 125(10), 577-581 (1999).
96. Gasparini G, Longo R, Fanelli M, Teicher BA. Combination of antiangiogenic therapy with other anticancer therapies: results, challenges, and open questions. J. Clin. Oncol. 23(6), 1295-1311 (2005).
97. D'Adamo DR, Anderson SE, Albritton K et al. Phase II study of doxorubicin and bevacizumab for patients with metastatic soft-tissue sarcomas. J. Clin. Oncol. 23(28), 7135-7142 (2005).
98. Verschraegen CF, Quinn R, Rabinowitz I, Arias-Pulido H, Muller C. Phase I/II study of docetaxel (D), gemcitabine (G), and bevacizumab (B) in patients (pts) with advanced or recurrent soft tissue sarcoma (STS). J. Clin. Oncol. (Meeting Abstracts) 26(15 Suppl.), (2008) (Abstract 10534).
99. 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 study 62043). J. Clin. Oncol. 27(19), 3126-3132 (2009).
100. Maki RG, D'Adamo DR, Keohan ML et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J. Clin. Oncol. 27(19), 3133-3140 (2009).
101. Vigil CE, Chiappori AA, Williams CA et al. Phase II study of sunitinib malate (SM) in subjects with metastatic and/or surgically unresectable non-GIST soft tissue sarcomas. J. Clin. Oncol. 26(15 Suppl.), (2008) (Abstract 10535).
102. Hensley ML, Sill MW, Scribner DR et al. Sunitinib malate in the treatment of recurrent or persistent uterine leiomyosarcoma: a Gynecologic Oncology Group Phase II Study. Gynecol. Oncol. 115(3), 460-465 (2009).
103. Fleming G. Gemcitabine/docetaxel - welcome to a new standard. Gynecol. Oncol. 109(3), 313-315 (2008).
104. Soria J, Lazar V, Lassau N et al. Sorafenib (S) and dacarbazine (D) combination in patients (pts) with advanced malignant solid tumors: Phase I study with tumor biopsy genomic analysis and dynamic contrast enhanced ultrasonography (DCE-US). J. Clin. Oncol. 25(18 Suppl.), (2007) (Abstract 3556).
105. Dupont J, Rothenberg ML, Spriggs DR et al. Safety and pharmacokinetics of intravenous VEGF Trap in a Phase I clinical trial of patients with advanced solid tumors. J. Clin. Oncol. 23(16 Suppl.), (2005) (Abstract 3029).
106. Hernando E, Charytonowicz E, Dudas ME et al. The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Nat. Med. 13(6), 748-753 (2007).
107. Hu J, Khanna V, Jones M, Surti U. Genomic alterations in uterine leiomyosarcomas: potential markers for clinical diagnosis and prognosis. Genes Chromosomes Cancer 31(2), 117-124 (2001).
108. Chawla SP, Tolcher AW, Staddon AP et al. Survival results with AP23573, a novel mTOR inhibitor, in patients (pts) with advanced soft tissue or bone sarcomas: update of Phase II trial. J. Clin. Oncol. 25(18 Suppl.), (2007) (Abstract 10076).
109. Jones CL, Holmgren E. An adaptive Simon two-stage design for Phase 2 studies of targeted therapies. Contemp. Clin. Trials 28(5), 654-661 (2007).
110. Verweij J. Soft tissue sarcoma trials: one size no longer fits all. J. Clin. Oncol. 27(19), 3085-3087 (2009).
111. Ren B, Yu YP, Jing L et al. Gene expression analysis of human soft tissue leiomyosarcomas. Hum. Pathol. 34(6), 549-558 (2003).
112. Rushing RS, Shajahan S, Chendil D et al. Uterine sarcomas express KIT protein but lack mutation(s) in exon 11 or 17 of c-KIT. Gynecol. Oncol. 91(1), 9-14 (2003).
113. Kushner DM, Webster KD, Belinson JL, Rybicki LA, Kennedy AW, Markman M. Safety and efficacy of adjuvant single-agent ifosfamide in uterine sarcoma. Gynecol. Oncol. 78(2), 221-227 (2000).
114. Gadducci A, Landoni F, Sartori E et al. Uterine leiomyosarcoma: analysis of treatment failures and survival. Gynecol. Oncol. 62(1), 25-32 (1996).
115. Wu TI, Chang TC, Hsueh S et al. Prognostic factors and impact of adjuvant chemotherapy for uterine leiomyosarcoma. Gynecol. Oncol. 100(1), 166-172 (2006).
116. A Phase II study assessing adjuvant treatment of high-risk uterine leiomyosarcoma with gemcitabine/docetaxel, followed by doxorubicin (SARC005). The Sarcoma Alliance for Research through Collaboration (SARC). www.sarctrials.org/SARC005 (Accessed 2 September 2009)
117. The NCCN Clinical Practice Guidelines in Oncology™ Uterine Cancer (Version 2.2009) www.nccn.org/professionals/physician-gls/PDF/uterine.pdf. (Accessed 28 August 2009)
118. Trabectedin in treating patients with advanced, persistent, or recurrent leiomyosarcoma of the uterus http://clinicaltrials.gov/ct2/show/NCT00379145 (Accessed 5 October 2009)
119. Phase III randomized study of doxorubicin with versus without ifosfamide and pegfilgrastim in patients with locally advanced or metastatic soft tissue sarcoma www.cancer.gov/clinicaltrials/EORTC-62012 (Accessed 5 October 2009)
120. Phase II evaluation of ifosfamide plus doxorubicin & filgrastim versus gemcitabine plus docetaxel & filgrastim in the treatment of localized poor prognosis soft tissue sarcoma http://clinicaltrials.gov/ct2/show/ NCT00189137 (Accessed 10 September 2009)
121. Phase II trial of sorafenib and dacarbazine in soft tissue sarcoma http://clinicaltrials.gov/ct2/show/NCT00837148 (Accessed 10 September 2009)