{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:16:19Z","timestamp":1791278179165,"version":"4.1.0"},"reference-count":10,"publisher":"S. Karger AG","issue":"1-2","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncology"],"published-print":{"date-parts":[[2011]]},"abstract":"<i>Purpose:<\/i> The purpose of this study was to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics and preliminary activity of TH-302, a hypoxia-activated prodrug, in combination with doxorubicin in patients with advanced soft tissue sarcoma. <i>Patients and Methods:<\/i> TH-302 was administered intravenously on days 1 and 8 and doxorubicin 75 mg\/m<sup>2<\/sup> on day 1 (2 h after TH-302) of every 3-week cycle. TH-302 starting dose was 240 mg\/m<sup>2<\/sup> with a classic 3 + 3 dose escalation. Pharmacokinetics were assessed on days 1 and 8 of cycle 1. Tumor assessments were performed after every second cycle. <i>Results:<\/i> Sixteen patients enrolled. Prophylactic growth factor support was added due to grade 4 neutropenia. The MTD was 300 mg\/m<sup>2<\/sup>. DLTs at 340 mg\/m<sup>2<\/sup> were neutropenia-associated infection and grade 4 thrombocytopenia. Common adverse events included fatigue, nausea and skin rash. There was no evidence of pharmacokinetic interaction between TH-302 and doxorubicin. Five of 15 (33%) evaluable patients had a partial response by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. <i>Conclusions:<\/i> The hematologic toxicity of doxorubicin is increased when combined with TH-302. This can be mitigated by prophylactic growth factor support. Toxicities were manageable and there was evidence of antitumor activity.<\/jats:p>","DOI":"10.1159\/000327739","type":"journal-article","created":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T07:54:44Z","timestamp":1306914884000},"page":"50-56","source":"Crossref","is-referenced-by-count":70,"title":["A Phase I Study of the Safety and Pharmacokinetics of the Hypoxia-Activated Prodrug TH-302 in Combination with Doxorubicin in Patients with Advanced Soft Tissue Sarcoma"],"prefix":"10.1159","volume":"80","author":[{"given":"Kristen N.","family":"Ganjoo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee D.","family":"Cranmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Butrynski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rushing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Adkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott H.","family":"Okuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Lorente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stew","family":"Kroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia K.","family":"Langmuir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sant P.","family":"Chawla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2011,5,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1007%2Fs00259-002-1096-7"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1054%2Fbjoc.2001.1728"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1093%2Fjnci%2F92.3.205"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1200%2FJCO.2006.09.7717"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1200%2FJCO.2008.19.2930"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1155%2FS1357714X00000062"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1158%2F1078-0432.CCR-05-1664"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1200%2FJCO.2005.01.3771"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1101%2Fgad.1243304"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.2967%2Fjnumed.107.045914"}],"container-title":["Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/327739","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/327739","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/327739","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T19:15:26Z","timestamp":1745435726000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000327739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011]]},"references-count":10,"journal-issue":{"issue":"1-2","published-online":{"date-parts":[[2011,6,1]]},"published-print":{"date-parts":[[2011,6,28]]}},"URL":"https:\/\/doi.org\/10.1159\/000327739","archive":["Portico"],"relation":{},"ISSN":["0030-2414","1423-0232"],"issn-type":[{"value":"0030-2414","type":"print"},{"value":"1423-0232","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011]]}}}