ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review.Journal of the American Heart Association · 2017Pooled it
- Hypophosphatemia as a Potential Class Effect of Histone Deacetylase Inhibitors: Evidence from Disproportionality Analysis and Mendelian Randomization Analysis of Drug Targets.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Review
- Comprehensive characterization of respiratory genes based on a computational framework in pan-cancer to develop stratified treatment strategies.PLoS computational biology · 2025Article
- A phase 1b study of venetoclax and alvocidib in patients with relapsed/refractory acute myeloid leukemia.Hematological oncology · 2023Article
- Functional Drug Screening of Small Molecule Inhibitors of Epigenetic Modifiers in Refractory AML Patients.Cancers · 2022Article
- Electrophysiology Translational Considerations in Cardio-Oncology: QT and Beyond.Journal of cardiovascular translational research · 2020Review
- HDAC Inhibitors in Acute Myeloid Leukemia.Cancers · 2019Review
- QT Interval Prolongation Associated With Cytotoxic and Targeted Cancer Therapeutics.Current treatment options in oncology · 2019Review
- Myeloid cell leukemia-1 dependence in acute myeloid leukemia: a novel approach to patient therapy.Oncotarget · 2019Review
- New advances in targeted gastric cancer treatment.World journal of gastroenterology · 2016Review
- Update on rational targeted therapy in AML.Blood reviews · 2016Review
- Molecular targeted therapy for the treatment of gastric cancer.Journal of experimental & clinical cancer research : CR · 2016Review
- The quest for an effective and safe personalized cell therapy using epigenetic tools.Clinical epigenetics · 2016Review
- A phase 1 study of vorinostat maintenance after autologous transplant in high-risk lymphoma.Leukemia & lymphoma · 2015Article
- Rational Combinations of Targeted Agents in AML.Journal of clinical medicine · 2015Review
- Histone deacetylase inhibitor (HDACI) mechanisms of action: emerging insights.Pharmacology & therapeutics · 2014Review
- Managing Tumor Lysis Syndrome in the Era of Novel Cancer Therapies.Journal of the advanced practitioner in oncologyReview
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
purposeThis phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination. EXPERIMENTAL
designPatients received vorinostat (200 mg orally, three times a day, for 14 days) on a 21-day cycle, combined with 2 different alvocidib administration schedules: a 1-hour intravenous infusion, daily × 5; or a 30-minute loading infusion followed by a 4-hour maintenance infusion, weekly × 2. The alvocidib dose was escalated using a standard 3+3 design.
resultsTwenty-eight patients were enrolled and treated. The alvocidib MTD was 20 mg/m(2) (30-minute loading infusion) followed by 20 mg/m(2) (4-hour maintenance infusion) on days one and eight, in combination with vorinostat. The most frequently encountered toxicities were cytopenias, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, and QT prolongation. Dose-limiting toxicities (DLT) were cardiac arrhythmia-atrial fibrillation and QT prolongation. No objective responses were achieved although 13 of 26 evaluable patients exhibited stable disease. Alvocidib seemed to alter vorinostat pharmacokinetics, whereas alvocidib pharmacokinetics were unaffected by vorinostat. Ex vivo exposure of leukemia cells to plasma obtained from patients after alvocidib treatment blocked vorinostat-mediated p21(CIP1) induction and downregulated Mcl-1 and p-RNA Pol II for some specimens, although parallel in vivo bone marrow responses were infrequent.
conclusionsAlvocidib combined with vorinostat is well tolerated. Although disease stabilization occurred in some heavily pretreated patients, objective responses were not obtained with these schedules.
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Registered trials
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