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A Phase I, Dose-Finding Study in Patients with Advanced Solid Malignancies of the Oral γ-Secretase Inhibitor PF-03084014

Overview of attention for article published in Clinical Cancer Research, January 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • High Attention Score compared to outputs of the same age and source (87th percentile)

Mentioned by

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1 news outlet
twitter
3 tweeters
patent
1 patent
facebook
1 Facebook page

Citations

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148 Dimensions

Readers on

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59 Mendeley

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Title
A Phase I, Dose-Finding Study in Patients with Advanced Solid Malignancies of the Oral γ-Secretase Inhibitor PF-03084014
Published in
Clinical Cancer Research, January 2015
DOI 10.1158/1078-0432.ccr-14-0607
Pubmed ID
25231399
Authors

Wells A. Messersmith, Geoffrey I. Shapiro, James M. Cleary, Antonio Jimeno, Arvind Dasari, Bo Huang, M. Naveed Shaik, Rossano Cesari, Xianxian Zheng, Jennifer M. Reynolds, Patricia A. English, Karen R. McLachlan, Kenneth A. Kern, Patricia M. LoRusso

Abstract

Purpose: To estimate the maximum tolerated dose (MTD) for continuous oral administration of the gamma-secretase inhibitor PF-03084014, determine the recommended phase 2 dose (RP2D), and evaluate safety and preliminary activity in patients with advanced solid tumors. Experimental Design: This open-label, phase I study consisted of a dose-finding portion based on a 3+3 design, followed by an expansion cohort. PF-03084014 was administered orally, twice daily (BID) for 21 continuous days. Tested doses ranged from 20 to 330 mg BID. In the expansion cohort, patients were to receive the estimated MTD or a lower dose of PF-03084014. Results: A total of 64 patients received treatment. The MTD was estimated to be 220 mg BID. The RP2D was determined to be 150 mg BID, based on the better safety profile versus the 220-mg BID dose, given comparable NOTCH-related target inhibition. The most common treatment-related AEs were diarrhea, nausea, fatigue, hypophosphatemia, vomiting, rash, and decreased appetite, which were generally mild to moderate in severity. One patient with advanced thyroid cancer had a complete response and five of seven response-evaluable patients with desmoid tumor achieved a partial response (71.4% objective response rate). Tumor responses were mostly durable, ranging from 1.74+ to 24+ months. PF-03084014 demonstrated a generally dose-dependent pharmacokinetic profile at doses ranging from 20 to 330 mg BID. Consistent down-modulation of NOTCH-related HES4 gene expression was observed in peripheral blood from all evaluable patients. Conclusions: Further development of PF-03084014 for the treatment of patients with advanced solid tumors is warranted and currently under evaluation.

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Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
France 1 2%
Unknown 57 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 22%
Researcher 10 17%
Student > Bachelor 5 8%
Other 5 8%
Student > Doctoral Student 4 7%
Other 12 20%
Unknown 10 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 15 25%
Medicine and Dentistry 13 22%
Biochemistry, Genetics and Molecular Biology 9 15%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Nursing and Health Professions 2 3%
Other 5 8%
Unknown 13 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 14. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 May 2022.
All research outputs
#2,069,720
of 21,407,661 outputs
Outputs from Clinical Cancer Research
#1,693
of 12,195 outputs
Outputs of similar age
#23,708
of 222,908 outputs
Outputs of similar age from Clinical Cancer Research
#19
of 139 outputs
Altmetric has tracked 21,407,661 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,195 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.2. This one has done well, scoring higher than 86% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 222,908 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 139 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.

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