Treatment of Advanced, Metastatic Soft Tissue Sarcoma: Latest Evidence and Clinical Considerations

Overview

Journal Ther Adv Med Oncol

Specialty Oncology

Date 2017 Aug 11

PMID 28794805

Citations 47

Authors

Gino K In

James S Hu

William W Tseng

Affiliations

Soon will be listed here.

Abstract

Soft tissue sarcoma (STS) is a biologically heterogeneous malignancy with over 50 subtypes. Historically, there have been few systemic treatment options for this relatively rare disease. Traditional cytotoxic agents, such as anthracyclines, alkylating agents, and taxanes have limited clinical benefit beyond the first-line setting; across all high-grade STS subtypes, median overall survival remains approximately 12-18 months for advanced metastatic disease. The development of targeted therapies has led to recent US Food and Drug Administration approval of four new treatments for high-grade STS in the advanced metastatic setting. Among these, olaratumab is most notable for its improvement in overall survival for patients with anthracycline-naïve disease. Further progress in STS management will rely on novel trial design, subtype-specific therapies and validation of biomarkers to tailor therapy. Immunotherapy has shown promise as a new, but yet undiscovered frontier in the management of STS.

Citing Articles

Correlation between METTL3 overexpression and F-FDG uptake in patients with soft tissue sarcoma.

Wu T, Xie J, Feng H, Zhang H, Tao J, Chen B BMC Cancer. 2025; 25(1):27.

PMID: 39773621 PMC: 11708263. DOI: 10.1186/s12885-024-13419-8.

A Case of Unresectable Pulmonary Artery Intimal Sarcoma with Prolonged Survival by Chemotherapy.

Noguchi T, Gomi D, Fukushima T, Ozawa T, Kobayashi T, Sekiguchi N Case Rep Oncol. 2024; 12(1):192-198.

PMID: 39263344 PMC: 11387848. DOI: 10.1159/000496334.

Case report: Pulmonary artery sarcoma diagnosed through rare brain metastases.

Tan N, Ouyang Z, Duan X, Zhou X, Zhu Y, Chu J Front Oncol. 2024; 14():1394708.

PMID: 38817902 PMC: 11138151. DOI: 10.3389/fonc.2024.1394708.

Phase Ib Study of Unesbulin (PTC596) Plus Dacarbazine for the Treatment of Locally Recurrent, Unresectable or Metastatic, Relapsed or Refractory Leiomyosarcoma.

Van Tine B, Ingham M, Attia S, Meyer C, Baird J, Brooks-Asplund E J Clin Oncol. 2024; 42(20):2404-2414.

PMID: 38684039 PMC: 11227303. DOI: 10.1200/JCO.23.01684.

Correlation between F-FDG PET-derived parameters and quantitative pathological characteristics of soft tissue sarcoma.

Chen B, Tao J, Wu T, Feng H, Xie J, Zhong L Quant Imaging Med Surg. 2023; 13(12):7842-7853.

PMID: 38106249 PMC: 10721999. DOI: 10.21037/qims-23-412.

References

Edmonson J, Ryan L, Blum R, Brooks J, Shiraki M, Frytak S . Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993; 11(7):1269-75. DOI: 10.1200/JCO.1993.11.7.1269. View

Patel S, Vadhan-Raj S, Papadopolous N, Plager C, Burgess M, Hays C . High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence. J Clin Oncol. 1997; 15(6):2378-84. DOI: 10.1200/JCO.1997.15.6.2378. View

van Kesteren C, de Vooght M, Lopez-Lazaro L, Mathot R, Schellens J, Jimeno J . Yondelis (trabectedin, ET-743): the development of an anticancer agent of marine origin. Anticancer Drugs. 2003; 14(7):487-502. DOI: 10.1097/00001813-200308000-00001. View

Rossi R, Godde A, Kleinebrand A, Riepenhausen M, Boos J, Ritter J . Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity: analysis of 120 patients. J Clin Oncol. 1994; 12(1):159-65. DOI: 10.1200/JCO.1994.12.1.159. View

Herzog J, von Klot-Heydenfeldt F, Jabar S, Ranft A, Rossig C, Dirksen U . Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity. Sarcoma. 2016; 2016:7461783. PMC: 5098094. DOI: 10.1155/2016/7461783. View

Lawrence M, Stojanov P, Polak P, Kryukov G, Cibulskis K, Sivachenko A . Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013; 499(7457):214-218. PMC: 3919509. DOI: 10.1038/nature12213. View

Chu Q, Mita A, Forouzesh B, Tolcher A, Schwartz G, Nieto A . Phase I and pharmacokinetic study of sequential paclitaxel and trabectedin every 2 weeks in patients with advanced solid tumors. Clin Cancer Res. 2010; 16(9):2656-65. DOI: 10.1158/1078-0432.CCR-10-0062. View

Nielsen O, Judson I, van Hoesel Q, Le Cesne A, Keizer H, Blay J . Effect of high-dose ifosfamide in advanced soft tissue sarcomas. A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2000; 36(1):61-7. DOI: 10.1016/s0959-8049(99)00240-3. View

Oosten A, Seynaeve C, Schmitz P, den Bakker M, Verweij J, Sleijfer S . Outcomes of first-line chemotherapy in patients with advanced or metastatic leiomyosarcoma of uterine and non-uterine origin. Sarcoma. 2010; 2009:348910. PMC: 2801456. DOI: 10.1155/2009/348910. View

10.

Germano G, Frapolli R, Simone M, Tavecchio M, Erba E, Pesce S . Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res. 2010; 70(6):2235-44. DOI: 10.1158/0008-5472.CAN-09-2335. View

11.

Martin-Liberal J, Alam S, Constantinidou A, Fisher C, Khabra K, Messiou C . Clinical activity and tolerability of a 14-day infusional Ifosfamide schedule in soft-tissue sarcoma. Sarcoma. 2013; 2013:868973. PMC: 3867825. DOI: 10.1155/2013/868973. View

12.

Tseng W, Malu S, Zhang M, Chen J, Sim G, Wei W . Analysis of the intratumoral adaptive immune response in well differentiated and dedifferentiated retroperitoneal liposarcoma. Sarcoma. 2015; 2015:547460. PMC: 4326351. DOI: 10.1155/2015/547460. View

13.

De Sanctis R, Bertuzzi A, Basso U, Comandone A, Marchetti S, Marrari A . Non-pegylated liposomal doxorubicin plus ifosfamide in metastatic soft tissue sarcoma: results from a phase-II trial. Anticancer Res. 2015; 35(1):543-7. View

14.

Schuetze S, Bolejack V, Choy E, Ganjoo K, Staddon A, Chow W . Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor. Cancer. 2016; 123(1):90-97. DOI: 10.1002/cncr.30379. View

15.

Sleijfer S, Ouali M, Van Glabbeke M, Krarup-Hansen A, Rodenhuis S, Cesne A . Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European Organization for Research.... Eur J Cancer. 2009; 46(1):72-83. DOI: 10.1016/j.ejca.2009.09.022. View

16.

Maki R, Jungbluth A, Gnjatic S, Schwartz G, DAdamo D, Keohan M . A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial Sarcoma. Sarcoma. 2013; 2013:168145. PMC: 3608267. DOI: 10.1155/2013/168145. View

17.

DeVito N, Henderson E, Han G, Reed D, Bui M, Lavey R . Clinical Characteristics and Outcomes for Solitary Fibrous Tumor (SFT): A Single Center Experience. PLoS One. 2015; 10(10):e0140362. PMC: 4607370. DOI: 10.1371/journal.pone.0140362. View

18.

Penel N, Glabbeke M, Mathoulin-Pelissier S, Judson I, Sleijfer S, Bui B . Performance status is the most powerful risk factor for early death among patients with advanced soft tissue sarcoma: the European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (STBSG) and French Sarcoma Group.... Br J Cancer. 2011; 104(10):1544-50. PMC: 3101912. DOI: 10.1038/bjc.2011.136. View

19.

Cerny T, Leyvraz S, von Briel T, Kupfer A, Schaad R, Schmitz S . Saturable metabolism of continuous high-dose ifosfamide with mesna and GM-CSF: a pharmacokinetic study in advanced sarcoma patients. Swiss Group for Clinical Cancer Research (SAKK). Ann Oncol. 1999; 10(9):1087-94. DOI: 10.1023/a:1008386000547. View

20.

Nakano K, Motoi N, Inagaki L, Tomomatsu J, Gokita T, Ae K . Differences in the responses to pazopanib and the prognoses of soft tissue sarcomas by their histological eligibility for the PALETTE study. Jpn J Clin Oncol. 2015; 45(5):449-55. DOI: 10.1093/jjco/hyv022. View