{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:27:02Z","timestamp":1791307622882,"version":"4.3.1"},"reference-count":12,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,4]],"date-time":"2013-03-04T00:00:00Z","timestamp":1362355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:p>There are few effective therapies for high\u2010risk sarcomas. Initial chemosensitivity is often followed by relapse. <jats:italic>In vitro<\/jats:italic>, mammalian target of rapamycin (mTOR) inhibition potentiates the efficacy of chemotherapy on resistant sarcoma cells. Although sarcoma trials using mTOR inhibitors have been disappointing, these drugs were used as maintenance. We conducted a Phase I\/II clinical trial to test the ability of temsirolimus to potentiate the cytotoxic effect of liposomal doxorubicin and present here the dose\u2010finding portion of this study. Adult and pediatric patients with recurrent or refractory sarcomas were treated with increasing doses of liposomal doxorubicin and temsirolimus using a continual reassessment method for escalation, targeting a dose\u2010limiting toxicity rate of 20%. Blood samples were drawn before and after the first dose of temsirolimus in Cycles 1 and 2 for pharmacokinetic analysis. The maximally tolerated dose combination was liposomal doxorubicin 30 mg\/m<jats:sup>2<\/jats:sup> monthly with temsirolimus 20 mg\/m<jats:sup>2<\/jats:sup> weekly. Hematologic toxicity was common but manageable. Dose\u2010limiting toxicities were primarily renal. Concurrent administration of liposomal doxorubicin resulted in increased exposure to sirolimus, the active metabolite of temsirolimus. Thus, the combination of liposomal doxorubicin and temsirolimus is safe for heavily pretreated sarcoma patients. Co\u2010administration with liposomal doxorubicin did not alter temsirolimus pharmacokinetics, but increased exposure to its active metabolite.<\/jats:p>","DOI":"10.1002\/ijc.28083","type":"journal-article","created":{"date-parts":[[2013,2,5]],"date-time":"2013-02-05T08:36:44Z","timestamp":1360053404000},"page":"997-1005","source":"Crossref","is-referenced-by-count":40,"title":["A dose\u2010finding study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcoma"],"prefix":"10.1002","volume":"133","author":[{"given":"K.A.","family":"Thornton","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.R.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.M.","family":"Trucco","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.A.","family":"Wilky","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Gul","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.A.","family":"Carrera\u2010Haro","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Fogle","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Shafique","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.D.","family":"Powell","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.F.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.M.","family":"Loeb","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3126"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.648"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013943"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199700544-00006"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.35.6329"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25928"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1191\/1740774506cn134oa"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050763"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780141102"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.2307\/2531628"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00050-8"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(84)90007-4"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.28083","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.28083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T06:15:28Z","timestamp":1700633728000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.28083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,4]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,8,15]]}},"alternative-id":["10.1002\/ijc.28083"],"URL":"https:\/\/doi.org\/10.1002\/ijc.28083","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,4]]}}}