ArticleBMC cancer2018
Safety and tolerability of quizartinib, a FLT3 inhibitor, in advanced solid tumors: a phase 1 dose-escalation trial.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01049893 (A Phase 1 Open-Label, Dose Finding, Safety and Tolerability Study of AC220 Administered Daily to Patients With Advanced Solid Tumors), which is not on this map. Cited by 7 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Open-Label, Dose Finding, Safety and Tolerability Study of AC220 Administered Daily to Patients With Advanced Solid Tumors
Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Quizartinib: a new hope in acute myeloid leukemia, an applied comprehensive review.Future oncology (London, England) · 2024Review
- Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas.Cancer medicine · 2023Article
- Screening and identification of potential biomarkers and therapeutic drugs in melanoma via integrated bioinformatics analysis.Investigational new drugs · 2021Article
- LT-171-861, a novel FLT3 inhibitor, shows excellent preclinical efficacy for the treatment of FLT3 mutant acute myeloid leukemia.Theranostics · 2021Article
- Antitumor Activity of a Novel Tyrosine Kinase Inhibitor AIU2001 Due to Abrogation of the DNA Damage Repair in Non-Small Cell Lung Cancer Cells.International journal of molecular sciences · 2019Article
- Effects of VEGFR1Journal of cancer research and clinical oncology · 2019Article
- Quizartinib (AC220): a promising option for acute myeloid leukemia.Drug design, development and therapy · 2019Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundQuizartinib, an inhibitor of class III receptor tyrosine kinases (RTKs), is currently in phase 3 development for the treatment of acute myeloid leukemia (AML) bearing internal tandem duplications in the FLT3 gene. Aberrant RTK signaling is implicated in the pathogenesis of a variety of solid tumors, suggesting that inhibiting quizartinib-sensitive RTKs may be beneficial in precision cancer therapy.
methodsThis was a phase 1, open-label, modified Fibonacci dose-escalation study of orally administered quizartinib in patients with advanced solid tumors whose disease progressed despite standard therapy or for which there was no available standard treatment. Patients received quizartinib dihydrochloride (henceforth referred to as quizartinib) once daily throughout a 28-day treatment cycle. The primary endpoint was evaluation of the maximum tolerated dose (MTD) of quizartinib. Secondary endpoints included preliminary evidence of antitumor activity and determination of the pharmacokinetic and pharmacodynamic parameters of quizartinib.
resultsThirteen patients were enrolled. Five patients received a starting dose of quizartinib 135 mg/day; dose-limiting toxicities (DLTs) of grade 3 pancytopenia, asymptomatic grade 3 QTc prolongation, and febrile neutropenia were observed in 1 patient each at this dose. A lower dose of quizartinib (90 mg/day [n = 8]) was administered without DLTs. The most common treatment-related treatment-emergent adverse events (AEs) were fatigue (n = 7, 54%), dysgeusia (n = 5, 38%), neutropenia (n = 3, 23%), and QTc prolongation (n = 3, 23%). Overall, all patients experienced at least 1 AE, and 4 experienced serious AEs (2 patients each in the 135-mg and 90-mg dose groups) including hematologic AEs, infections, and gastrointestinal disorders. Six patients (including 3 patients with gastrointestinal stromal tumors [GIST]) had a best response of stable disease.
conclusionThe MTD of quizartinib in patients with advanced solid tumors was 90 mg/day. Overall, the safety and tolerability of quizartinib were manageable, with no unexpected AEs. Quizartinib monotherapy had limited evidence of activity in this small group of patients with advanced solid tumors.
trial registrationClinical Trials Registration Number: NCT01049893 ; First Posted: January 15, 2010.
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