ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
A phase I, pharmacokinetic, and pharmacodynamic study of panobinostat, an HDAC inhibitor, combined with erlotinib in patients with advanced aerodigestive tract tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review.Journal of the American Heart Association · 2017Pooled it
- HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives.RSC advances · 2026Review
- Clinical progress and functional modalities of HDAC inhibitor-based combination therapies in cancer treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets.Journal of translational medicine · 2024Review
- DNA and histone modifications as potent diagnostic and therapeutic targets to advance non-small cell lung cancer management from the perspective of 3P medicine.The EPMA journal · 2022Review
- Histone deacetylases modulate resistance to the therapy in lung cancer.Frontiers in genetics · 2022Review
- Senescence marker protein 30 inhibits tumor growth by reducing HDAC4 expression in non-small cell lung cancer.Translational lung cancer research · 2021Article
- Histone Modification in NSCLC: Molecular Mechanisms and Therapeutic Targets.International journal of molecular sciences · 2021Review
- [Research Progress of Epigenetic Mechanism in Acquired Resistance of Targeted Therapy in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- Review
- Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives.Cancers · 2021Review
- Therapeutic strategies of different HPV status in Head and Neck Squamous Cell Carcinoma.International journal of biological sciences · 2021Review
- Article
- Platinum-based combination chemotherapy triggers cancer cell death through induction of BNIP3 and ROS, but not autophagy.Journal of cellular and molecular medicine · 2020Article
- Epigenetic polypharmacology: A new frontier for epi-drug discovery.Medicinal research reviews · 2020Review
- Engineering Multidimensional Evolutionary Forces to Combat Cancer.Cancer discovery · 2019Review
- Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.Cancers · 2019Review
- Impact of Epigenetic Regulation on Head and Neck Squamous Cell Carcinoma.Journal of dental research · 2019Article
- EMT-Mediated Acquired EGFR-TKI Resistance in NSCLC: Mechanisms and Strategies.Frontiers in oncology · 2019Review
- Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression.Cancer discovery · 2018Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
purposePanobinostat, a histone deacetylase (HDAC) inhibitor, enhances antiproliferative activity in non-small cell lung cancer (NSCLC) cell lines when combined with erlotinib. We evaluated this combination in patients with advanced NSCLC and head and neck cancer. EXPERIMENTAL
designEligible patients were enrolled in a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) of twice weekly panobinostat plus daily erlotinib at four planned dose levels (DL). Pharmacokinetics, blood, fat pad biopsies (FPB) for histone acetylation, and paired pre and posttherapy tumor biopsies for checkpoint kinase 1 (CHK1) expression were assessed.
resultsOf 42 enrolled patients, 33 were evaluable for efficacy. Dose-limiting toxicities were prolonged-QTc and nausea at DL3. Adverse events included fatigue and nausea (grades 1-3), and rash and anorexia (grades 1-2). Disease control rates were 54% for NSCLC (n = 26) and 43% for head and neck cancer (n = 7). Of 7 patients with NSCLC with EGF receptor (EGFR) mutations, 3 had partial response, 3 had stable disease, and 1 progressed. For EGFR-mutant versus EGFR wild-type patients, progression-free survival (PFS) was 4.7 versus 1.9 months (P = 0.43) and overall survival was 41 (estimated) versus 5.2 months (P = 0.39). Erlotinib pharmacokinetics was not significantly affected. Correlative studies confirmed panobinostat's pharmacodynamic effect in blood, FPB, and tumor samples. Low CHK1 expression levels correlated with PFS (P = 0.006) and response (P = 0.02).
conclusionsWe determined MTD at 30 mg (panobinostat) and 100 mg (erlotinib). Further studies are needed to further explore the benefits of HDAC inhibitors in patients with EGFR-mutant NSCLC, investigate FPB as a potential surrogate source for biomarker investigations, and validate CHK1's predictive role.
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