{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T22:34:22Z","timestamp":1789857262836,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T00:00:00Z","timestamp":1422921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000869","name":"Susan G. Komen for the Cure","doi-asserted-by":"publisher","award":["M124188\/BCTR0707898"],"award-info":[{"award-number":["M124188\/BCTR0707898"]}],"id":[{"id":"10.13039\/100000869","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001513","name":"Breast Cancer Alliance","doi-asserted-by":"publisher","award":["M123863"],"award-info":[{"award-number":["M123863"]}],"id":[{"id":"10.13039\/100001513","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The optimal weekly oral dose of sirolimus and intravenous nanoparticle albumin\u2013bound paclitaxel (<jats:italic>nab<\/jats:italic>\u2010paclitaxel) were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>A phase 1b study was performed to evaluate escalating doses of oral sirolimus (5\u201060 mg) on days 2, 9, and 16 with intravenous <jats:italic>nab<\/jats:italic>\u2010paclitaxel (100 mg\/m<jats:sup>2<\/jats:sup>) on days 1, 8, and 15 in a 28\u2010day cycle. A run\u2010in treatment of <jats:italic>nab<\/jats:italic>\u2010paclitaxel (day \u221214) and sirolimus (day \u22127) was administered for pharmacokinetic and pharmacodynamic assessments. Clinical trial endpoints included dose\u2010limiting toxicities (DLTs), maximum tolerated doses, and response rates. Pharmacodynamics included immunohistochemistry for phosphatase and tensin homolog, mammalian target of rapamycin (mTOR), AKT, phosphorylated AKT, S6K1, and phosphorylated S6K1; exploratory gene expression analysis; and [<jats:sup>18<\/jats:sup>F]fludeoxyglucose (FDG) positron emission tomography.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Twenty\u2010three patients with advanced solid tumors were treated. Fifteen patients had prior taxane therapy. Twenty\u2010two patients were evaluable for responses. One patient had a complete response, and 5 patients had a partial response (3 confirmed). DLTs were seen in 1 patient each at 10 (grade 3 dyspnea\/hypoxia) and 40 mg (grade 4 leukopenia\/neutropenia) and in 2 patients at 60 mg (grade 3 fatigue and grade 4 pericardial effusion). Patients with higher expression of posttreatment AKT and a greater decline in FDG activity were more likely to have a treatment response or stable disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Sirolimus showed an acceptable safety profile at a weekly dose of 40 mg with weekly intravenous <jats:italic>nab<\/jats:italic>\u2010paclitaxel at 100 mg\/m<jats:sup>2<\/jats:sup> on days 1, 8, and 15 every 28 days. The posttreatment AKT score and changes in FDG activity may have roles as early predictors of responses to mTOR inhibitors. <jats:bold><jats:italic>Cancer<\/jats:italic> 2015;121:1817\u20131826.<\/jats:bold> \u00a9 <jats:italic>2015 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.29254","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T11:26:57Z","timestamp":1422962817000},"page":"1817-1826","source":"Crossref","is-referenced-by-count":15,"title":["Phase 1b study of the mammalian target of rapamycin inhibitor sirolimus in combination with nanoparticle albumin\u2013bound paclitaxel in patients with advanced solid tumors"],"prefix":"10.1002","volume":"121","author":[{"given":"Maysa M.","family":"Abu\u2010Khalaf","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A.","family":"Baumgart","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University of Rochester Rochester New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott N.","family":"Gettinger","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indukala","family":"Doddamane","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Tuck","sequence":"additional","affiliation":[{"name":"EMD Serono Billerica Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihe","family":"Hou","sequence":"additional","affiliation":[{"name":"Celgene Corporation Berkeley Heights New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianhang","family":"Chen","sequence":"additional","affiliation":[{"name":"Celgene Corporation Berkeley Heights New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Lezon\u2010Geyda","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zelterman","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Hatzis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Digiovanna","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Azodi","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsay N.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Case Western University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2062"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.cco.0000143964.74936.d1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602162"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207542"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp038141"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0110"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199448050-00009"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199504133321507"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304369"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.11.013"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.5848"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.937"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clbc.2012.05.001"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0361"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1158\/1535-7163.1605.3.12","article-title":"Akt upregulation increases resistance to microtubule\u2010directed chemotherapeutic agents through mammalian target of rapamycin","volume":"3","author":"VanderWeele D","year":"2004","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.12.018"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/clinchem\/43.3.539","article-title":"A limited sampling strategy for estimating sirolimus area\u2010under\u2010the\u2010concentration curve","volume":"43","author":"Kaplan B","year":"1997","journal-title":"Clin Chem"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm791"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-29362-0_23"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1052"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2925"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(02)00662-8"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2904"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.12.004"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(99)00229-4"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(03)00073-X"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.102"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2004.00026.x"},{"key":"e_1_2_7_30_1","first-page":"2887","article-title":"Pharmacodynamic evaluation of CCI\u2010779, an inhibitor of mTOR, in cancer patients","volume":"9","author":"Peralba JM","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.3033"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24837"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1996.0227"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.29254","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.29254","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T18:12:34Z","timestamp":1760292754000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.29254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,3]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1002\/cncr.29254"],"URL":"https:\/\/doi.org\/10.1002\/cncr.29254","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,3]]}}}