Abstract:
:Background To determine the recommended dose (RD) of a combination of PM01183 and gemcitabine in patients with advanced solid tumors. Methods Forty-five patients received escalating doses of PM01183/gemcitabine on Days 1 and 8 every 3 weeks (d1,8 q3wk) following a standard 3 + 3 design. Results PM01183 3.5 mg flat dose (FD)/gemcitabine 1000 mg/m2 was the highest dose level tested. Dose-limiting toxicities (DLTs) were mostly hematological and resulted in the expansion of a lower dose level (PM01183 3.5 mg FD/gemcitabine 800 mg/m2); 19 patients at this dose level were evaluable but >30% had DLT and >20% had febrile neutropenia. No DLT was observed in 11 patients treated at PM01183 3.0 mg FD/gemcitabine 800 mg/m2, which was defined as the RD. This regimen was feasible and tolerable with manageable toxicity; mainly grade 3/4 myelosuppression. Non-hematological toxicity comprised fatigue, nausea, vomiting, and transaminases increases. Fifteen (33%) patients received ≥6 cycles with no cumulative hematological toxicity. Pharmacokinetic analysis showed no evidence of drug-drug interaction. Nine of 38 patients had response as per RECIST (complete [3%] and partial [21%]), for an overall response rate (ORR) of 24% (95% Confidence Interval [CI] 12-40%). Eleven patients (29%) had disease stabilization ≥4 months. Responses were durable (median of 8.5 months): overall median progression-free survival (PFS) was 4.2 months (95% CI, 2.7-6.5 months). Conclusions The RD for this combination is PM01183 3.0 mg FD (or 1.6 mg/m2)/gemcitabine 800 mg/m2 d1,8 q3wk. This schedule is well tolerated and has antitumor activity in several advanced solid tumor types.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Paz-Ares L,Forster M,Boni V,Szyldergemajn S,Corral J,Turnbull S,Cubillo A,Teruel CF,Calderero IL,Siguero M,Bohan P,Calvo Edoi
10.1007/s10637-016-0410-3subject
Has Abstractpub_date
2017-04-01 00:00:00pages
198-206issue
2eissn
0167-6997issn
1573-0646pii
10.1007/s10637-016-0410-3journal_volume
35pub_type
杂志文章,多中心研究abstract::Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 ...
journal_title:Investigational new drugs
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doi:10.1007/s10637-017-0498-0
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journal_title:Investigational new drugs
pub_type: 杂志文章,评审
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journal_title:Investigational new drugs
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doi:10.1007/s10637-008-9156-x
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journal_title:Investigational new drugs
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abstract::Idarubicin, a new analogue of daunorubicin, was administered to 27 patients with advanced breast cancer in a phase II trial. The drug was given orally at a dose of 30-35 mg/m2 every 3 weeks. Twenty-two patients were evaluable for response. All evaluable patients were previously treated with one or more chemotherapeuti...
journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章,评审
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章,评审
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章
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更新日期:2020-06-01 00:00:00
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章
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更新日期:2013-10-01 00:00:00
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journal_title:Investigational new drugs
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journal_title:Investigational new drugs
pub_type: 杂志文章
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journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
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