Abstract：
BACKGROUND:The vascular disrupting agent ombrabulin shows synergy with docetaxel in vivo. Recommended phase II doses were determined in a dose escalation study in advanced solid tumours. METHODS:Ombrabulin (30-min infusion, day 1) followed by docetaxel (1-h infusion, day 2) every 3 weeks was explored. Ombrabulin was escalated from 11.5 to 42 mg m(-2) with 75 mg m(-2) docetaxel, then from 30 to 35 mg m(-2) with 100 mg m(-2) docetaxel. Recommended phase II dose cohorts were expanded. RESULTS:Fifty-eight patients were treated. Recommended phase II doses were 35 mg m(-2) ombrabulin with 75 mg m(-2) docetaxel (35/75 mg m(-2); 13 patients) and 30 mg m(-2) ombrabulin with 100 mg m(-2) docetaxel (30/100 mg m(-2); 16 patients). Dose-limiting toxicities were grade 3 fatigue (two patients; 42/75, 35/100), grade 3 neutropaenic infection (25/75), grade 3 headache (42/75), grade 4 febrile neutropaenia (30/100), and grade 3 thrombosis (35/100). Toxicities were consistent with each agent; mild nausea/vomiting, asthaenia/fatigue, alopecia, and anaemia were common, as were neutropaenia and leukopaenia. Diarrhoea, nail disorders and neurological symptoms were frequent at 100 mg m(-2) docetaxel. Pharmacokinetic analyses did not show any relevant drug interactions. Ten patients had partial responses (seven at 30 mg m(-2) ombrabulin), eight lasting >3 months. CONCLUSIONS:Sequential administration of ombrabulin with 75 or 100 mg m(-2) docetaxel every 3 weeks is feasible.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Eskens FA,Tresca P,Tosi D,Van Doorn L,Fontaine H,Van der Gaast A,Veyrat-Follet C,Oprea C,Hospitel M,Dieras Vdoi
10.1038/bjc.2014.137subject
Has Abstractpub_date
2014-04-29 00:00:00pages
2170-7issue
9eissn
0007-0920issn
1532-1827pii
bjc2014137journal_volume
110pub_type
杂志文章abstract：:The association between breast and endometrial cancer was investigated in a cohort consisting of 60,065 subjects (99% of all women in whom a first breast cancer was diagnosed in Sweden in 1960-63 and 1968-81). Complete follow-up until 1981 revealed a total of 260 endometrial cancers, as against an expected number of 1...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1987.16
更新日期：1987-01-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1900
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journal_title：British journal of cancer
pub_type： 杂志文章
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更新日期：2013-05-28 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.406
更新日期：1991-11-01 00:00:00
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pub_type： 杂志文章
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1977.154
更新日期：1977-07-01 00:00:00
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pub_type： 杂志文章
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.401
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pub_type： 杂志文章
doi：10.1038/bjc.2017.55
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journal_title：British journal of cancer
pub_type： 杂志文章
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更新日期：2014-02-04 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.631
更新日期：2015-02-03 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.125
更新日期：1995-03-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604048
更新日期：2007-11-19 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.39
更新日期：2011-03-29 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1987.9
更新日期：1987-01-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.444
更新日期：1993-11-01 00:00:00
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pub_type： 杂志文章
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.63
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doi：10.1038/sj.bjc.6602722
更新日期：2005-09-05 00:00:00
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pub_type： 杂志文章
doi：10.1038/bjc.1984.71
更新日期：1984-04-01 00:00:00
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doi：10.1038/sj.bjc.6602535
更新日期：2005-04-25 00:00:00
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pub_type： 杂志文章
doi：10.1038/sj.bjc.6605348
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pub_type： 杂志文章,meta分析
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更新日期：1992-10-01 00:00:00
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journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
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doi：10.1038/sj.bjc.6605641
更新日期：2010-04-13 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.329
更新日期：1995-08-01 00:00:00
