| Title |
Clinical pharmacodynamic/exposure characterisation of the multikinase inhibitor ilorasertib (ABT-348) in a phase 1 dose-escalation trial
|
|---|---|
| Published in |
British Journal of Cancer, March 2018
|
| DOI | 10.1038/s41416-018-0020-2 |
| Pubmed ID | |
| Authors |
Michael L. Maitland, Sarina Piha-Paul, Gerald Falchook, Razelle Kurzrock, Ly Nguyen, Linda Janisch, Sanja Karovic, Mark McKee, Elizabeth Hoening, Shekman Wong, Wijith Munasinghe, Joann Palma, Cherrie Donawho, Guinan K. Lian, Peter Ansell, Mark J. Ratain, David Hong |
| Abstract |
Ilorasertib (ABT-348) inhibits Aurora and VEGF receptor (VEGFR) kinases. Patients with advanced solid tumours participated in a phase 1 dose-escalation trial to profile the safety, tolerability, and pharmacokinetics of ilorasertib. Ilorasertib monotherapy was administered at 10-180 mg orally once daily (Arm I, n = 23), 40-340 mg orally twice daily (Arm II, n = 28), or 8-32 mg intravenously once daily (Arm III, n = 7), on days 1, 8, and 15 of each 28-day cycle. Dose-limiting toxicities were predominantly related to VEGFR inhibition. The most frequent treatment-emergent adverse events ( > 30%) were: fatigue (48%), anorexia (34%), and hypertension (34%). Pharmacodynamic markers suggested that ilorasertib engaged VEGFR2 and Aurora B kinase, with the VEGFR2 effects reached at lower doses and exposures than Aurora inhibition effects. In Arm II, one basal cell carcinoma patient (40 mg twice daily (BID)) and one patient with adenocarcinoma of unknown primary site (230 mg BID) had partial responses. In patients with advanced solid tumours, ilorasertib treatment resulted in evidence of engagement of the intended targets and antitumour activity, but with maximum inhibition of VEGFR family kinases occurring at lower exposures than typically required for inhibition of Aurora B in tissue. NCT01110486. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 43 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 7 | 16% |
| Student > Ph. D. Student | 6 | 14% |
| Researcher | 4 | 9% |
| Other | 3 | 7% |
| Student > Doctoral Student | 2 | 5% |
| Other | 5 | 12% |
| Unknown | 16 | 37% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 19% |
| Biochemistry, Genetics and Molecular Biology | 3 | 7% |
| Nursing and Health Professions | 3 | 7% |
| Immunology and Microbiology | 2 | 5% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Other | 6 | 14% |
| Unknown | 19 | 44% |
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 19 March 2018.
All research outputs
#20,469,520
of 23,028,364 outputs
Outputs from British Journal of Cancer
#10,095
of 10,483 outputs
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#293,486
of 332,288 outputs
Outputs of similar age from British Journal of Cancer
#95
of 98 outputs
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