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A phase I study of high-dose rosuvastatin with standard dose erlotinib in patients with advanced solid malignancies

Overview of attention for article published in Journal of Translational Medicine, March 2016
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Title
A phase I study of high-dose rosuvastatin with standard dose erlotinib in patients with advanced solid malignancies
Published in
Journal of Translational Medicine, March 2016
DOI 10.1186/s12967-016-0836-6
Pubmed ID
Authors

Glenwood D. Goss, Derek J. Jonker, Scott A. Laurie, Johanne I. Weberpals, Amit M. Oza, Johanna N. Spaans, Charles la Porte, Jim Dimitroulakos

Abstract

Synergistic cytotoxicity with high-dose statins and erlotinib has been demonstrated in preclinical models across a number of tumour types. In this phase I study, we evaluated the safety and potential anti-tumour activity of escalating doses of rosuvastatin in combination with the standard clinical dose of erlotinib in heavily pretreated patients with advanced solid tumours. This was a single-center, phase I open-label study to determine the safety and recommended phase two dose (RPTD) of rosuvastatin in combination with 150 mg/day standard dose of erlotinib. Using a 3 + 3 study design and 28-day cycle, escalating doses of rosuvastatin from 1 to 8 mg/kg/day ×2 weeks (cycle 1) and 3 weeks (subsequent cycles) given concurrently with erlotinib were evaluated. In order to expand the experience and to gain additional safety and pharmacokinetic data, two expansions cohorts using concurrent or alternating weekly dosing regimens at the RPTD were also evaluated. All 24 patients enrolled were evaluable for toxicity, and 22 for response. The dose-limiting toxicity (DLT) of reversible muscle toxicity was seen at the 2 mg/kg/day dose level. Maximal tolerated dose (MTD) was determined to be 1 mg/kg/day. Thirty-three percent of patients developed at least 1≥ grade 2 muscle toxicity (rhabdomyolysis: 1/24, myalgia: 7/24) resulting in one study-related death. Durable stable disease for more than 170 days was seen in 25 % of patients that received concurrent treatment and were evaluable for response (n = 16). Plasma erlotinib levels on study were unaffected by the addition of rosuvastatin. The observed disease stabilization rate of 25 % with combination therapy in this heavily pretreated population is encouraging, however, the high levels of muscle toxicities observed limited this combination strategy.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 2%
Unknown 51 98%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 9 17%
Student > Master 8 15%
Student > Ph. D. Student 5 10%
Student > Doctoral Student 4 8%
Researcher 3 6%
Other 10 19%
Unknown 13 25%
Readers by discipline Count As %
Medicine and Dentistry 11 21%
Pharmacology, Toxicology and Pharmaceutical Science 5 10%
Biochemistry, Genetics and Molecular Biology 5 10%
Agricultural and Biological Sciences 3 6%
Nursing and Health Professions 3 6%
Other 8 15%
Unknown 17 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 31 March 2016.
All research outputs
#3,847,522
of 7,471,181 outputs
Outputs from Journal of Translational Medicine
#955
of 1,713 outputs
Outputs of similar age
#148,300
of 272,895 outputs
Outputs of similar age from Journal of Translational Medicine
#49
of 82 outputs
Altmetric has tracked 7,471,181 research outputs across all sources so far. This one is in the 27th percentile – i.e., 27% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,713 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
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 272,895 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 82 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.