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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EPatients with locally advanced unresectable or metastatic soft tissue sarcoma have poor outcomes. Palliative chemotherapy is standard treatment for these patients, but it generally results in considerable toxicity. Previous studies have compared single-agent doxorubicin with doxorubicin plus ifosfamide, but the optimal doses remain unclear. This article discusses the European Organisation for Research and Treatment of Cancer 62012 Phase 3 study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00061984\u0026amp;atom=%2Fspmdc%2F12%2F15%2F9.2.atom\u0022\u003ENCT00061984\u003C\/a\u003E] in patients with advanced soft tissue sarcoma.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ESoft Tissue Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EPatients with locally advanced unresectable or metastatic soft tissue sarcoma have poor outcomes. Palliative chemotherapy is standard treatment for these patients, but it generally results in considerable toxicity. Previous studies have compared single-agent doxorubicin with doxorubicin plus ifosfamide, but the optimal doses remain unclear. The European Organisation for Research and Treatment of Cancer (EORTC) 62012 Phase 3 study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00061984\u0026amp;atom=%2Fspmdc%2F12%2F15%2F9.2.atom\u0022\u003ENCT00061984\u003C\/a\u003E] presented by Winette van der Graaf, MD, PhD, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands, compared single-agent doxorubicin (75 mg\/m\u003Csup\u003E2\u003C\/sup\u003E) with doxorubicin (75 mg\/m\u003Csup\u003E2\u003C\/sup\u003E) plus ifosfamide (7.5 g\/m\u003Csup\u003E2\u003C\/sup\u003E) in patients with advanced soft tissue sarcoma (ASTS).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EA total of 455 patients with high-grade ASTS were randomized to doxorubicin (n=228) versus doxorubicin plus ifosfamide plus pegfilgrastim (n=227). Patients were stratified according to age, performance status, liver metastases, and histologic grade. The most common histologic diagnoses were liposarcoma, leiomyosarcoma, and synovial sarcoma. The primary endpoint was overall survival (OS). The secondary endpoints were response, toxicity, and treatment-related mortality. The median follow-up was 56 months. An improvement in survival was defined as clinically significant if 1-year survival was at least 10% higher in the combination arm, corresponding with an HR \u0026lt;0.737. Allocated treatment was started by 217 patients in the doxorubicin arm and 215 patients in the combination arm.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThere was no significant difference in OS with doxorubicin versus combination treatment (HR, 0.83; 95.5% CI, 0.67 to 1.03; p=0.076; \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). At 1year, OS was 51% in the doxorubicin arm versus 60% in the combination arm. The median OS was 12.8 months with single-agent doxorubicin versus 14.3 months with combination treatment. Progression-free survival (PFS) was significantly better in the combination arm compared with the doxorubicin arm (HR, 0.74; 95% CI, 0.60 to 0.90; p=0.003). The median PFS was 4.6 months with single-agent doxorubicin versus 7.4 months with doxorubicin plus ifosfamide. Patients treated with single-agent doxorubicin versus the combination had a complete response rate of 0.4% versus 1.8%, partial response rate of 13.2% versus 24.7%, and overall response rate of 13.6% versus 26.5%, respectively (\u003Ca id=\u0022xref-fig-1-2\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/9.2\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Response Rates with Single Agent Versus Combination Therapy.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1562751550\u0022 data-figure-caption=\u0022Response Rates with Single Agent Versus Combination Therapy.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/9.2\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/9.2\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/15\/9.2\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14253\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EResponse Rates with Single Agent Versus Combination Therapy.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EDoxo=single-agent doxorubicin; Dxlf=doxorubicin plus ifosfamide.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-6\u0022\u003EPatients treated with doxorubicin plus ifosfamide versus single-agent doxorubicin had considerably higher rates of grade 3 or higher adverse events, including neutropenia (41.5% vs 37.2%), leukopenia (43.3% vs 17.9%), febrile neutropenia (45.9% vs 13.5%), anemia (34.9% vs 4.6%), and thrombocytopenia (33.5% vs 0.4%), respectively. A total of 121 patients in the doxorubicin arm versus 109 patients in the combination arm discontinued treatment because of progression of disease (PD) or death from PD (41.7% vs 20.7%); toxicity, including toxic death (2.6% vs 17.6%); patient refusal (1.8% vs 4.4%); death not related to malignant disease or toxicity (1.8% vs 0.4%); and other reasons (5.3% vs 4.8%), respectively.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThe combination of doxorubicin and ifosfamide doubled the response rate and significantly improved PFS but did not significantly improve OS in patients with high-grade ASTS. Doxorubicin combined with ifosfamide was considerably more toxic than single-agent doxorubicin. The investigators concluded that single-agent doxorubicin should remain the standard treatment for this population.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/15\/9.2.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzn7sq\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn7sq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}