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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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\u003EThe results of a National Surgical Adjuvant Breast and Bowel Project [NSABP; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00096278\u0026amp;atom=%2Fspmdc%2F8%2F4%2F5.atom\u0022\u003ENCT00096278\u003C\/a\u003E trial indicate that bevacizumab is safe when it is given as postoperative adjuvant therapy (in conjunction with conventional chemotherapy) to patients with stage II or stage III colorectal cancer. The efficacy data from the study are not yet available, but the safety data were reported first because of the potential effect on ongoing or planned investigations that involve bevacizumab and other antiangiogenic agents.\u003C\/p\u003E\n\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EGastrointestinal Cancers\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EAdjuvant\/Neoadjuvant Therapy\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe results of a National Surgical Adjuvant Breast and Bowel Project (NSABP) (\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00096278\u0026amp;atom=%2Fspmdc%2F8%2F4%2F5.atom\u0022\u003ENCT00096278\u003C\/a\u003E) trial indicate that bevacizumab is safe when it is given as postoperative adjuvant therapy (in conjunction with conventional chemotherapy) to patients with stage II or stage III colorectal cancer. The efficacy data from the study are not yet available, but the safety data were reported first because of the potential effect on ongoing or planned investigations that involve bevacizumab and other antiangiogenic agents.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ECarmen J. Allegra, MD, University of Florida, Gainesville, FL, reported the initial safety data from NSABP C-08. This randomized phase 3 trial was designed to compare modified FOLFOX6 (5-FU\/leucovorin plus oxaliplatin) with and without bevacizumab. The primary endpoint was disease-free survival. One of the most important findings of the safety analysis, said Dr. Allegra, is that bevacizumab is safe in the postoperative period in the patient population that is eligible for C-08. It is not clear how far the data can or should be extrapolated beyond the eligible population. \u201cThe fear has been that, as an antiangiogenic agent, bevacizumab could have serious toxicity for postoperative patients. This was not borne out in the study,\u201d he said.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe trial enrolled 2710 patients who were randomly assigned to either FOLFOX6 every 2 weeks for 12 doses or the same chemotherapy regimen with bevacizumab given every 2 weeks for 26 doses. Patients were assigned to a treatment group after Day 29 and before Day 50 postoperatively. The data that were presented by Dr. Allegra represented findings for 1321 patients who were treated with FOLFOX6 alone and 1326 who were treated with FOLFOX6 plus bevacizumab. The mean duration of follow-up was 28.5 months.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe addition of bevacizumab did not adversely affect the dose intensity of FOLFOX6. Dr. Allegra noted that the median dose intensity was 40.6 mg\/m2\/wk for FOLFOX6 alone and 41.6 mg\/m2\/wk for FOLFOX6 plus bevacizumab (p=0.13). A significantly greater percentage of patients who were treated with FOLFOX6 plus bevacizumab received at least 10 of the 12 doses of 5-FU (85% vs 80%; p\u0026lt;0.01) and oxaliplatin (78% vs 73%; p\u0026lt;0.01).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EDr. Allegra reported that bevacizumab was not associated with a significant increase in several toxicities that have been found in other studies of advanced disease, such as cardiac, central nervous system, or peripheral arterial ischemia; gastrointestinal perforation; or hemorrhage. Bevacizumab was associated with significantly fewer occurrences of thrombocytopenia (1.4% vs 3.4% for FOLFOX6 alone; p\u0026lt;0.001) and allergic reaction (3.1% vs 4.7%; p=0.03).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThere was no difference between the early mortality in each group. Within 6 months of random assignment, the mortality rate was 0.96% for FOLFOX6 alone and 0.90% for FOLFOX6 plus bevacizumab (p=1.0). At 18 months, the corresponding mortality rates were 1.33% and 1.35% (p=1.0).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EMost of the adverse events were grade 3, and these events occurred in significantly more patients in the FOLFOX6 plus bevacizumab group (p=0.0006). All of the adverse events were manageable, added Dr. Allegra. To isolate the effects of bevacizumab, the researchers evaluated adverse events that occurred in the 12 months that followed the completion of chemotherapy (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Focusing on wound complications, Dr. Allegra noted that all such complications were grade 3 and that they resulted in surgical intervention in all but one case and in discontinuation of bevacizumab in half of the cases. Most of the wound complications (63%) were symptomatic abdominal incisional hernias, and 37% was dehiscence, infection, or inflammation at the site of the infusion port. The median time to occurrence of the wound complications was 5 months for hernias and 2 months for the infusion port-related complications.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/10955\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/10955\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10955\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\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003ESignificantly Different Toxicities (Grade 3 or Higher) 12 Months After Completion of Chemotherapy.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EDr. Allegra concluded that despite the safety of bevacizumab, it cannot be recommended in the adjuvant setting until data provide evidence of its efficacy.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EIn his discussion of the study, Richard M. Goldberg, MD, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, said that he agreed that bevacizumab was safe in the setting of adjuvant therapy for stage II or III colorectal cancer. He pointed out that the rates of early mortality were similar to those in other adjuvant studies.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EDr. Goldberg commented that the increased frequency of pain among patients who were treated with bevacizumab was a surprise. However, he added, \u201cThere have been some studies of other angiogenesis inhibitors in which patients have reported modest pain.\u201d In closing, he reiterated the need for more data to determine the long-term toxicity or benefit of bevacizumab.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2008 MD Conference Express\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\/8\/4\/5.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_openurl.js?nzmfbq\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_tables.js?nzmfbq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}