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Article: Phase 1-2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma

TitlePhase 1-2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma
Authors
KeywordsAdvanced hepatocellular carcinoma
Angiogenesis
Doxorubicin
PTK787
Issue Date2010
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
Citation
Cancer, 2010, v. 116 n. 21, p. 5022-5029 How to Cite?
AbstractBackground: This phase 1-2 trial assessed the efficacy and tolerability of an oral angiogenesis inhibitor-PTK787/ZK222584 (PTK)-in combination with intravenous doxorubicin for the treatment of advanced hepatocellular carcinoma (HCC) patients. METHODS: In phase 1, advanced HCC patients received PTK at escalating doses together with doxorubicin 60 mg/m 2 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. RESULTS: 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, 23-73 years), and 63 percent of patients were chronic hepatitis B carriers. Notably, the majority of patients had Child-Pugh 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-free survival was 5.4 months (range, 0.27-23.6 months), and overall survival was 7.3 months (range, 0.8-23.6 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. Conclusions: The combination of PTK with intravenous doxorubicin shows encouraging activity in treating advanced HCC patients. © 2010 American Cancer Society.
Persistent Identifierhttp://hdl.handle.net/10722/129386
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID
Funding AgencyGrant Number
Novartis
University of Hong Kong
Funding Information:

Supported by a research grant from Novartis and the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorYau, Ten_HK
dc.contributor.authorChan, Pen_HK
dc.contributor.authorPang, Ren_HK
dc.contributor.authorNg, Ken_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorPoon, RTen_HK
dc.date.accessioned2010-12-23T08:36:37Z-
dc.date.available2010-12-23T08:36:37Z-
dc.date.issued2010en_HK
dc.identifier.citationCancer, 2010, v. 116 n. 21, p. 5022-5029en_HK
dc.identifier.issn0008-543Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/129386-
dc.description.abstractBackground: This phase 1-2 trial assessed the efficacy and tolerability of an oral angiogenesis inhibitor-PTK787/ZK222584 (PTK)-in combination with intravenous doxorubicin for the treatment of advanced hepatocellular carcinoma (HCC) patients. METHODS: In phase 1, advanced HCC patients received PTK at escalating doses together with doxorubicin 60 mg/m 2 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. RESULTS: 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, 23-73 years), and 63 percent of patients were chronic hepatitis B carriers. Notably, the majority of patients had Child-Pugh 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-free survival was 5.4 months (range, 0.27-23.6 months), and overall survival was 7.3 months (range, 0.8-23.6 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. Conclusions: The combination of PTK with intravenous doxorubicin shows encouraging activity in treating advanced HCC patients. © 2010 American Cancer Society.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741en_HK
dc.relation.ispartofCanceren_HK
dc.rightsCancer. Copyright © John Wiley & Sons, Inc.-
dc.subjectAdvanced hepatocellular carcinomaen_HK
dc.subjectAngiogenesisen_HK
dc.subjectDoxorubicinen_HK
dc.subjectPTK787en_HK
dc.titlePhase 1-2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-543X&volume=116&issue=21&spage=5022&epage=5029&date=2010&atitle=Phase+1-2+trial+of+PTK787/ZK222584+combined+with+intravenous+doxorubicin+for+treatment+of+patients+with+advanced+hepatocellular+carcinoma:+implication+for+antiangiogenic+approach+to+hepatocellular+carcinoma-
dc.identifier.emailYau, T: tyaucc@hku.hken_HK
dc.identifier.emailPang, R: robertap@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailPoon, RT: poontp@hkucc.hku.hken_HK
dc.identifier.authorityYau, T=rp01466en_HK
dc.identifier.authorityPang, R=rp00274en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityPoon, RT=rp00446en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/cncr.25372en_HK
dc.identifier.pmid20629034-
dc.identifier.scopuseid_2-s2.0-78249288161en_HK
dc.identifier.hkuros179082en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78249288161&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume116en_HK
dc.identifier.issue21en_HK
dc.identifier.spage5022en_HK
dc.identifier.epage5029en_HK
dc.identifier.isiWOS:000283397700018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYau, T=23391533100en_HK
dc.identifier.scopusauthoridChan, P=7403497841en_HK
dc.identifier.scopusauthoridPang, R=7004376659en_HK
dc.identifier.scopusauthoridNg, K=7403179075en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridPoon, RT=7103097223en_HK

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