ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Phase I study of panobinostat plus everolimus in patients with relapsed or refractory lymphoma.
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 47 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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 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
- Duvelisib plus romidepsin in relapsed/refractory T cell lymphomas: a phase 1b/2a trial.Nature medicine · 2024Trial
- Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia.Clinical epigenetics · 2019Trial
- A Phase I/II Trial of Panobinostat in Combination With Lenalidomide in Patients With Relapsed or Refractory Hodgkin Lymphoma.Clinical lymphoma, myeloma & leukemia · 2017Trial
- Epigenetics: rethinking of drug research and development.Future medicinal chemistry · 2024Article
- Epigenetic targets in B- and T-cell lymphomas: latest developments.Therapeutic advances in hematology · 2023Review
- Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates.Molecules (Basel, Switzerland) · 2022Review
- Review
- Regulation of B-Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas.Cancers · 2022Review
- Romidepsin and lenalidomide-based regimens have efficacy in relapsed/refractory lymphoma: Combined analysis of two phase I studies with expansion cohorts.American journal of hematology · 2021Article
- Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer.BMC cancer · 2021Article
- Evolving therapeutic landscape in follicular lymphoma: a look at emerging and investigational therapies.Journal of hematology & oncology · 2021Review
- Telomerase Regulation: A Role for Epigenetics.Cancers · 2021Review
- Would the Recommended Dose Have Been Different Using Novel Dose-Finding Designs? Comparing Dose-Finding Designs in Published Trials.JCO precision oncology · 2021Article
- Recent Update of HDAC Inhibitors in Lymphoma.Frontiers in cell and developmental biology · 2020Review
- Genetic alterations and their clinical implications in DLBCL.Nature reviews. Clinical oncology · 2019Review
- Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma.International journal of molecular sciences · 2019Review
- Emerging epigenetic-modulating therapies in lymphoma.Nature reviews. Clinical oncology · 2019Review
- MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability inCancer discovery · 2019Article
- Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo evaluate the safety and efficacy of panobinostat plus everolimus in patients with relapsed Hodgkin and non-Hodgkin lymphoma. The concept was supported by the single-agent clinical activity of histone deacetylase inhibitors and mTOR inhibitors, and on the in vitro mechanism-based synergistic antiproliferative activity. EXPERIMENTAL
designThis was a phase I study in patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma using panobinostat orally on Monday/Wednesday/Friday and everolimus orally daily. Toxicity and responses were assessed in dose-escalation cohort followed by expansion cohort at maximum-tolerated dose. Exploratory analysis of serum cytokine levels was performed.
resultsThirty patients were enrolled onto four dose levels. The dose-limiting toxicity was thrombocytopenia. The maximal tolerated dose was panobinostat 20 mg and everolimus 10 mg. Grade 3/4 toxicity included thrombocytopenia (64%), neutropenia (47%), anemia (20%), infection (10%), fatigue (7%), and dyspnea (7%). A total of 10 patients (33%; indolent lymphoma, T-cell lymphoma, mantle cell lymphoma, and Hodgkin lymphoma) achieved objective responses. In patients with Hodgkin lymphoma (n = 14), the overall response rate was 43% with complete response rate of 15%. In patients with Hodgkin lymphoma, multiple serum cytokine levels decreased significantly after treatment with this combination therapy. Of note, clinical responses were associated with a decrease in serum interleukin-5 levels (day 8, P = 0.013, and day 15, P = 0.021).
conclusionsOur data suggest that the combination therapy is active but with significant thrombocytopenia. Future studies should explore alternate scheduling and different compounds that target the same pathways to improve the tolerability of this novel combination.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.