1. bookVolume 6 (2015): Issue 3 (September 2015)
Journal Details
First Published
14 Aug 2014
Publication timeframe
4 times per year
Open Access

The role of Pazopanib in Soft Tissue Sarcoma: A comprehensive review of the literature

Published Online: 17 Dec 2015
Volume & Issue: Volume 6 (2015) - Issue 3 (September 2015)
Page range: 13 - 21
Journal Details
First Published
14 Aug 2014
Publication timeframe
4 times per year

[1] Siegel R., Naishadham D., Jemal A. Cancer Statistics, 2012.CA Cancer J Clin.2012;62:10-2910.3322/caac.20138Search in Google Scholar

[2] Helman LJ, Meltzer P. Mechanisms of sarcoma development. NatureReviews Cancer 2003;3:685-94.Search in Google Scholar

[3] Brennan M, Singer S, Maki R, O’Sullivan B. Sarcomas of the soft tissueand bone. In: DeVita Jr VT, Hellman S, Rosenberg SA, editors. Cancer:Principles and Practice of Oncology, vol. 2, 7th edition Philadelphia:Lippincott Williams and Wilkins; 2004.Search in Google Scholar

[4] Clark MA, Fischer C, Judson I, Thomas JM. Softtissue sarcoma in adults. New England of Journal Medicine 2005;353:701-11.10.1056/NEJMra041866Search in Google Scholar

[5] Benjamin RS, Wiernik PH, Bachur NR. Adriamycin: a new effective agent in the therapy of disseminated sarcomas. Med Pediatr Oncol 1975; 1:63.10.1002/mpo.2950010109Search in Google Scholar

[6] Borden EC, Amato DA, Rosenbaum C, et al. Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 1987; 5:840.10.1200/JCO.1987.5.6.8403585441Search in Google Scholar

[7] Keohan ML, Taub RN. Chemotherapy for advanced sarcoma: therapeutic decisions and modalities. Semin Oncol 1997; 24:572.Search in Google Scholar

[8] Van Glabbeke M, Verweij J, Judson I, Nielsen OS. Progression-freerate as the primary endpoint for phase II study in soft tissue sarcoma.European Journal of Cancer 2002;38:543-9.10.1016/S0959-8049(01)00398-7Search in Google Scholar

[9] Verweij J, van Oosterom A, Blay JY, et al. Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J Cancer 2003; 39:2006.10.1016/S0959-8049(02)00836-5Search in Google Scholar

[10] 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 cancersoft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol 2009; 27:3126.10.1200/JCO.2008.21.3223Search in Google Scholar

[11] van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebocontrolled phase 3 trial. Lancet 2012; 379:1879.10.1016/S0140-6736(12)60651-5Search in Google Scholar

[12] Santoro A. Advanced soft tissue sarcoma:How many more trials with anthracyclines and ifosfamide? Ann Oncol. 1999;10:151-15410.1023/A:1008311913200Search in Google Scholar

[13] Borden EC, Amato DA, Rosenbaum C, et al. Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas. J Clin Oncol 1987; 5:840.10.1200/JCO.1987.5.6.840Search in Google Scholar

[14] Demetri GD, Elias AD. Results of single-agent and combination chemotherapy for advanced soft tissue sarcomas. Implications for decision making in the clinic. Hematol Oncol Clin North Am 1995; 9:765.10.1016/S0889-8588(18)30070-4Search in Google Scholar

[15] Grenader T, Goldberg A, Hadas-Halperin I, Gabizon A. Long-term response to pegylated liposomal doxorubicin in patients with metastatic soft tissue sarcomas. Anticancer Drugs 2009; 20:15.10.1097/CAD.0b013e3283198058Search in Google Scholar

[16] Patel SR, Vadhan-Raj S, Papadopolous N, et al. 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; 15:2378.10.1200/JCO.1997.15.6.2378Search in Google Scholar

[17] 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 2007; 25:3144.10.1200/JCO.2006.09.7717Search in Google Scholar

[18] Skubitz KM, Haddad PA. Paclitaxel and pegylatedliposomal doxorubicin are both active in angiosarcoma. Cancer 2005; 104:361.10.1002/cncr.21140Search in Google Scholar

[19] Casanova M, Ferrari A, Spreafico F, et al. Vinorelbine in previously treated advanced childhood sarcomas: evidence of activity in rhabdomyosarcoma. Cancer 2002; 94:3263.10.1002/cncr.10600Search in Google Scholar

[20] 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; 2006:15947.10.1155/SRCM/2006/15947Search in Google Scholar

[21] Omura GA, Major FJ, Blessing JA, et al. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer 1983; 52:626.10.1002/1097-0142(19830815)52:4<626::AID-CNCR2820520409>3.0.CO;2-ESearch in Google Scholar

[22] Gottlieb JA, Benjamin RS, Baker LH, et al. Role of DTIC (NSC-45388) in the chemotherapy of sarcomas. Cancer Treat Rep 1976; 60:199.Search in Google Scholar

[23] Buesa JM, Mouridsen HT, van Oosterom AT, et al. High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group. Ann Oncol 1991; 2:307.10.1093/oxfordjournals.annonc.a057942Search in Google Scholar

[24] Garcia del Muro X, Lopez-Pousa A, Martin J, et al. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas. Cancer 2005; 104:1706.10.1002/cncr.21384Search in Google Scholar

[25] Zucali PA, Bertuzzi A, Parra HJ, et al. The «old drug» dacarbazine as a second/third line chemotherapy in advanced soft tissue sarcomas. Invest New Drugs 2008; 26:175.10.1007/s10637-007-9086-z17898927Search in Google Scholar

[26] Thigpen JT, Blessing JA, Beecham J, et al. 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 1991; 9:1962.10.1200/JCO.1991.9.11.19621941054Search in Google Scholar

[27] Goldstein D, Cheuvart B, Trump DL, et al. Phase II trial of carboplatin in soft-tissue sarcoma. Am J Clin Oncol 1990; 13:420.10.1097/00000421-199010000-000112220662Search in Google Scholar

[28] 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 2006; 119:706.10.1002/ijc.2186716496406Search in Google Scholar

[29] 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 [corrected]. J Clin Oncol 2007; 25:2755.10.1200/JCO.2006.10.411717602081Search in Google Scholar

[30] Penel N, Glabbeke MV, Mathoulin-Pelissier S, et al. 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 (FSG) study. Br J Cancer 2011; 104:1544.10.1038/bjc.2011.136310191221505457Search in Google Scholar

[31] 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 2005; 23:576.10.1200/JCO.2005.01.18015659504Search in Google Scholar

[32] 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 2004; 22:1480.10.1200/JCO.2004.02.09815084621Search in Google Scholar

[33] Hamberg P, Verweij J, Sleijfer S. (Pre-)clinical pharmacology andactivity of pazopanib, a novel multikinase angiogenesis inhibitor. TheOncologist 2010;15(6):539-47.10.1634/theoncologist.2009-0274322799420511320Search in Google Scholar

[34] Lammli J, Fan M, Rosenthal HG, et al. Expression of vascular endothelial growth factor correlates with the advance of clinical osteosarcoma.International Orthopaedics 2012;36(11):2307-13.10.1007/s00264-012-1629-z347929722855059Search in Google Scholar

[35] Kumar R, Knick VB, Rudolph SK, et al.Pharmacokinetic-pharmacodynamic correlation from mouse tohuman with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Molecular Cancer Therapeutics 2007;6:2012-21.10.1158/1535-7163.MCT-07-0193Search in Google Scholar

[36] [Podar K, Tonon G, Sattler M, et al. The smallmolecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proceedings of the National Academy of Science of the United States of America 2006;103:19478-83.10.1073/pnas.0609329103Search in Google Scholar

[37] Hurwitz HI, Dowlat A, Saini S, et al. Phase I trial of pazopanib in patients with advanced cancer. Clinical Cancer Research 2009;15:4220-7.10.1158/1078-0432.CCR-08-2740Search in Google Scholar

[38] Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase IIItrial. Journal of Clinical Oncology 2010;28:1061-8.10.1200/JCO.2009.23.9764Search in Google Scholar

[39] Hutson TE, Davis ID, Machiels JP, et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology 2010;28: 475-80.10.1200/JCO.2008.21.6994Search in Google Scholar

[40] Yau CC, Chen PJ, Chan P, et al. Phase I study of pazopanib in hepatocellular carcinoma: evaluation of clinical activity, pharmacokinetics and dynamic contrast enhanced MRI (DCE MRI). European Journal of Cancer 2009;7(Suppl 2):122.10.1016/S1359-6349(09)70418-5Search in Google Scholar

[41] Altorki N, Heymach J, Guarino M, et al. Phase II study of pazopanib (GW786034) given preoperatively in stage I-II non-small cell lung cancer (NSCLC): a proof-of-concept study. Annals of Oncology 2008;19(Suppl 8):89. Search in Google Scholar

[42] Friedlander M, Hancock KC, Benigno B, et al. Pazopanib (GW786034) is active in women with advanced epithelial ovarian, fallopian tube and peritoneal cancers: final results of a phase II study. Annals of Oncology 2008;19(Suppl 8):211.Search in Google Scholar

[43] Prince HM, Hönemann, Spencer A, et al. Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034). Blood 2009;113: 4819-20.10.1182/blood-2009-02-20720919423744Search in Google Scholar

[44] www.fda.gov. FDA approves Votrient for advanced soft tissue sarcoma.Search in Google Scholar

[45] B. Kasper, S. Sleijfer, S. Litière et al. Long-term responders and survivors on pazopanib for advanced soft tissue sarcomas: subanalysis of two European Organisation for Research and Treatmentof Cancer (EORTC) clinical trials 62043 and 62072. Annals of Oncology 25: 719-724, 2014Search in Google Scholar

[46] T.E. Delea, J. Amdahl, H.R. Nakhaipour, S.C. Manso, A. Wang, N. Fedor, A. Chit. Cost effectiveness of pazopanib in advanced soft-tissue sarcoma in Canada. Curr Oncol, Vo21, 2014.748-759;10.3747/co.21.1899425711925489263Search in Google Scholar

[47] George S, Blay JY, Casali PG, et al. Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur J Cancer 2009;45:1959-68.10.1016/j.ejca.2009.02.01119282169Search in Google Scholar

[48] Tariq MS, Agresta S, Vigil CE, et al. Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma. Int J Cancer 2011;129:1963-9.Search in Google Scholar

[49] Maki RG, D’Adamo DR, Keohan ML, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol 2009;27:3133-40.10.1200/JCO.2008.20.4495271693619451436Search in Google Scholar

[50] Bertuzzi A, Stroppa EM, Secondino S, et al. Efficacy and toxicity of sorafenib monotherapy in patients with advanced soft tissue sarcoma failing anthracycline-based chemotherapy. J Clin Oncol (Meeting Abstracts) 2010;28:10025.10.1200/jco.2010.28.15_suppl.10025Search in Google Scholar

[51] Ryan CW, Von Mehren M, Rankin CJ, et al. Phase II intergroup study of sorafenib in advanced soft tissue sarcomas (STS): SWOG 0505. J Clin Oncol (Meeting Abstracts) 2008;26:10532.10.1200/jco.2008.26.15_suppl.10532Search in Google Scholar

[52] D’Adamo DR, Keohan ML, Carvajal RD, et al. A phase II trial of sorafenib and dacarbazine in leiomyosarcoma , synovial sarcoma , and malignant peripheral nerve sheath tumor (MPNST). J Clin Oncol (Meeting Abstracts) 2011;29:10025.10.1200/jco.2011.29.15_suppl.10025Search in Google Scholar

[53] Ratain MJ, Schwartz GK, Oza AM, et al. Brivanib (BMS-582664) in advanced solid tumors (AST): results of a phase II randomized discontinuation trial (RDT). J Clin Oncol (Meeting Abstracts) 2011;29:3079.10.1200/jco.2011.29.15_suppl.3079Search in Google Scholar

[54] Schwartz GK, Maki RG, Ratain MJ, et al. Brivanib (BMS-582664) in advanced soft-tissue sarcoma (STS): biomarker and subset results of a phase II randomized discontinuation trial. J Clin Oncol (Meeting Abstracts) 2011;29:10000.10.1200/jco.2011.29.15_suppl.10000Search in Google Scholar

[55] Alice Levar, Louis Tass, Philippe A. Cassier. Emerging Therapies for Soft-Tissue Sarcomas. Hematol Oncol Clin N Am 27 (2013) 1063-1078Search in Google Scholar

[56] Hernando E, Charytonowicz E, Dudas ME, et al. The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Nat Med 2007;13:748-53.10.1038/nm156017496901Search in Google Scholar

[57] Gutierrez A, Snyder EL, Marino-Enriquez A, et al. Aberrant AKT activation drives welldifferentiated liposarcoma. Proc Natl Acad Sci U S A 2011;108:16386-91.10.1073/pnas.1106127108318269921930930Search in Google Scholar

[58] Friedrichs N, Trautmann M, Endl E, et al. Phosphatidylinositol-30-kinase/AKT signaling is essential in synovial sarcoma. Int J Cancer 2011;129:1564-75.10.1002/ijc.2582921128248Search in Google Scholar

[59] Setsu N, Yamamoto H, Kohashi K, et al. The Akt/ mammalian target of rapamycin pathway is activated and associated with adverse prognosis in soft tissue leiomyosarcomas.Cancer 2012;118:1637-48.10.1002/cncr.2644821837670Search in Google Scholar

[60] Barretina J, Taylor BS, Banerji S, et al. Subtypespecific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet 2010;42:715-21.10.1038/ng.619291150320601955Search in Google Scholar

[61] Schuetze SM, Zhao L, Chugh R, et al. Results of a phase II study of sirolimus and cyclophosphamide in patients with advanced sarcoma. Eur J Cancer 2012;48:1347-53.10.1016/j.ejca.2012.03.022Search in Google Scholar

[62] Richter S, Pink D, Hohenberger P, et al. Multicenter, triple-arm, single-stage, phase II trial to determine the efficacy and safety of everolimus (RAD001) in patientswith refractory bone or soft tissue sarcomas including GIST. J Clin Oncol(Meeting Abstracts) 2010;28:10038.Search in Google Scholar

[63] Quek R, Wang Q, Morgan JA, et al. Combination mTOR and IGF-1R inhibition: phase I trial of everolimus and figitumumab in patients with advanced sarcomas and other solid tumors. Clin Cancer Res 2011;17:871-9.10.1158/1078-0432.CCR-10-2621Search in Google Scholar

[64] El-Hashemite N, Zhang H, Henske EP, et al. Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma. Lancet 2003;361:1348-9. 10.1016/S0140-6736(03)13044-9Search in Google Scholar

[65] Pan CC, Chung MY, Ng KF, et al. Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol 2008;214:387-93.10.1002/path.228918085521Search in Google Scholar

[66] Kenerson H, Folpe AL, Takayama TK, et al. Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms. Hum Pathol 2007;38:1361-71.10.1016/j.humpath.2007.01.028272221917521703Search in Google Scholar

[67] Wagner AJ, Malinowska-Kolodziej I, Morgan JA, et al. Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors. J Clin Oncol 2010;28: 835-40.10.1200/JCO.2009.25.2981481002920048174Search in Google Scholar

[68] Italiano A, Delcambre C, Hostein I, et al. Treatment with the mTOR inhibitor temsirolimus in patients with malignant PEComa. Ann Oncol 2010;21:1135-7.10.1093/annonc/mdq04420215136Search in Google Scholar

[69] Pedersen JV, Benson C, Tunariu N, et al. A retrospective study from the Royal Marsden Hospital (RMH) of patients with malignant perivascular epithelioid cell tumors (PEComa) receiving treatment with sirolimus (SI) or temsirolimus (TSI). J Clin Oncol (Meeting Abstracts) 2012;30:10038.10.1200/jco.2012.30.15_suppl.10038Search in Google Scholar

Recommended articles from Trend MD