{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:33:34Z","timestamp":1761597214509,"version":"build-2065373602"},"reference-count":32,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2010,7,13]],"date-time":"2010-07-13T00:00:00Z","timestamp":1278979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>This phase 1\u20102 trial assessed the efficacy and tolerability of an oral angiogenesis inhibitor\u2014PTK787\/ZK222584 (PTK)\u2014in combination with intravenous doxorubicin for the treatment of advanced hepatocellular carcinoma (HCC) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>In phase 1, advanced HCC patients received PTK at escalating doses together with doxorubicin 60 mg\/m<jats:sup>2<\/jats:sup> given as an intravenous bolus every 3 weeks to establish the maximum tolerated dose (MTD). Subsequently, in phase 2, all patients received the same regimen with oral PTK at the MTD dose every 3 weeks for a maximum of 6 cycles.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>Nine patients were recruited in phase 1, with the MTD established as 750 mg daily. Overall, 27 patients received the regimen with PTK at 750 mg daily. The median age was 52 years (range, 23\u201073 years), and 63 percent of patients were chronic hepatitis B carriers. Notably, the majority of patients had Child\u2010Pugh B cirrhosis. The overall response rate was 26.0%, with all the responding patients having partial response. Another 20% of patients achieved stable disease for at least 12 weeks. The median progression\u2010free survival was 5.4 months (range, 0.27\u201023.6 months), and overall survival was 7.3 months (range, 0.8\u201023.6 months). The commonest grade 3 or 4 nonhematological toxicities were mucositis (11%) and alopecia (7%), respectively. Grade 3 or 4 neutropenia was observed in 7 (26%) patients; 2 had neutropenic sepsis.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>The combination of PTK with intravenous doxorubicin shows encouraging activity in treating advanced HCC patients. Cancer 2010. \u00a9 2010 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.25372","type":"journal-article","created":{"date-parts":[[2010,7,13]],"date-time":"2010-07-13T15:12:17Z","timestamp":1279033937000},"page":"5022-5029","source":"Crossref","is-referenced-by-count":20,"title":["Phase 1\u20102 trial of PTK787\/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma"],"prefix":"10.1002","volume":"116","author":[{"given":"Thomas","family":"Yau","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelvin","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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