Side Effects of panobinostat: A Synthesis of Findings from 23 Studies

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Original Abstract of the Article

Main Research Findings

Panobinostat is a histone deacetylase inhibitor (HDAC inhibitor) that has shown promising results in multiple cancer types. Panobinostat, as shown in 2 , has been shown to be effective in treating multiple myeloma in combination with bortezomib and dexamethasone. Panobinostat, as shown in 4 , has been shown to exhibit activity in a variety of hematological diseases, including cutaneous T-cell lymphoma (CTCL), Hodgkin lymphoma (HL), myeloma, and myeloid malignancies. In addition, as shown in 21 , panobinostat has been shown to be effective in treating triple-negative breast cancer (TNBC) in combination with rapamycin, an mTOR inhibitor. However, panobinostat, as shown in 17 , can affect the digestive system, male reproductive system, respiratory system, and blood system.

Reasons for Side Effects

Panobinostat's side effects are thought to be due to the mechanism of action of HDAC inhibitors. HDAC inhibitors inhibit histone deacetylase, which promotes histone acetylation. Histone acetylation has the effect of activating gene expression. Therefore, while HDAC inhibitors can inhibit the growth of cancer cells, they can also affect the function of normal cells.

Common Side Effects

Digestive System

According to 17 , panobinostat may cause side effects on the digestive system. Specifically, diarrhea, nausea, and vomiting have been reported. Also, according to 7 , panobinostat may enhance gastrointestinal toxicity in combination with TRAIL receptor agonists.

Male Reproductive System

According to 17 , panobinostat may cause side effects on the male reproductive system. Specifically, decreased sperm count has been reported.

Respiratory System

According to 17 , panobinostat may cause side effects on the respiratory system. Specifically, dyspnea has been reported.

Blood System

According to 17 , panobinostat may cause side effects on the blood system. Specifically, thrombocytopenia and leukopenia have been reported. In addition, according to 12 , panobinostat has been reported to cause grade 3-4 side effects such as thrombocytopenia (43.6%), anemia (7.9%), neutropenia (16.5%), and lymphopenia (8.1%).

Countermeasures for Side Effects

Digestive System

According to 16 , diarrhea caused by panobinostat is often severe enough to warrant dose reduction, delays, or discontinuation of chemotherapy. Treatment of diarrhea is often by dose reduction and discontinuation of the offending drug. However, the symptom fails to entirely resolve with these interventions and dose reductions place the individual at risk for disease progression. Best practices for diarrhea management in MM are poorly understood, but diarrhea symptoms impede patient adherence and undermine quality of life.

Others

According to 14 , accurate evaluation of treatment side effects, their prompt recognition and management is mandatory for all clinical hematologists.

Comparison Between Studies

Common Points

These studies show that panobinostat is effective in treating multiple myeloma. In addition, panobinostat may affect the digestive system, male reproductive system, respiratory system, and blood system.

Differences

These studies show that the frequency and severity of side effects of panobinostat vary. In addition, there are some studies on the side effects of panobinostat in combination therapy. For example, 7 shows that panobinostat may enhance gastrointestinal toxicity in combination with TRAIL receptor agonists.

Precautions for Applying to Real Life

Panobinostat is an effective drug for treating cancer, but it also carries the risk of side effects. When taking panobinostat, follow your doctor's instructions and consult your doctor immediately if you experience any side effects.

Limitations of Current Research

There is still insufficient research on the side effects of panobinostat. Also, methods for reducing the side effects of panobinostat have not yet been established.

Future Research Directions

It is necessary to develop methods to reduce the side effects of panobinostat. It is also necessary to further investigate the side effects of panobinostat.

Conclusion

Panobinostat is an effective drug for treating multiple myeloma, but it also carries the risk of side effects. When taking panobinostat, follow your doctor's instructions and consult your doctor immediately if you experience any side effects.

Literature analysis of 23 papers
Positive Content
22
Neutral Content
0
Negative Content
1
Article Type
1
3
2
12
23
1.

Toxicity of targeted therapy in non-small-cell lung cancer management.

Author: RicciardiSerena, TomaoSilverio, de MarinisFilippo

Lung cancer treatment
Dermatologic side effects
Vascular adverse effects

Targeted therapies, such as EGFR and VEGFR inhibitors, are promising treatments for non-small-cell lung cancer. While these therapies are generally well-tolerated, they can cause dermatologic side effects. Other agents in clinical development are also associated with toxicities.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

2.

Patient-reported outcomes of multiple myeloma patients treated with panobinostat after ≥2 lines of therapy based on the international phase 3, randomized, double-blind, placebo-controlled PANORAMA-1 trial.

Author: RichardsonPaul G, SchlossmanRobert L, RoyAnuja N, PanneerselvamAshok, AcharyyaSuddhasatta, SopalaMonika, LonialSagar

Improved myeloma symptoms
Stable quality of life
Initial worsening of symptoms
Treatment side effects

This study assessed patient-reported outcomes (PROs) in the phase 3 PANORAMA-1 trial, which evaluated panobinostat (PAN) in combination with bortezomib (BTZ) and dexamethasone (DEX) for the treatment of multiple myeloma. The study found that the addition of PAN to the BTZ+DEX regimen resulted in limited symptomatology and had no significant impact on patients' quality of life.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases.

Author: YoonSomy, EomGwang Hyeon

Cancer treatment
Cardiovascular disease treatment
Neurodegenerative disease treatment

HDAC inhibitors are a new class of anticancer drugs that regulate histone acetylation and have shown promising results in hematologic cancers. HDAC inhibitors are also being investigated for their potential benefits in treating neurodegenerative diseases, inflammatory disorders, and cardiovascular diseases.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

4.

Panobinostat in lymphoid and myeloid malignancies.

Author: KhotAmit, DickinsonMichael, PrinceH Miles

Cancer treatment

Panobinostat is a potent pan-histone inhibitor of HDAC enzymes implicated in cancer development and progression. It has demonstrated activity in hematological diseases such as cutaneous T-cell lymphoma (CTCL), Hodgkin lymphoma (HL), myeloma, and myeloid malignancies.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Romidepsin (FK228), A Histone Deacetylase Inhibitor and its Analogues in Cancer Chemotherapy.

Author: PojaniEftiola, BarloccoDaniela

Cancer treatment

HDAC inhibitors, including Romidepsin, Belinostat, Vorinostat, Panobinostat, and Chidamide, are approved by the FDA for cancer treatment due to their ability to modulate histone modification and affect tumor development.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

HDAC Inhibitors as Novel Anti-Cancer Therapeutics.

Author: De SouzaCristabelle, ChatterjiBiswa Prasun

Cancer treatment
HDAC inhibition
Toxic side effects

This review discusses patents for novel HDAC inhibitors that offer potential improvements over existing drugs. These new molecules show promise for treating various cancers by targeting specific HDAC isoforms and minimizing toxic side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

7.

Antitumor activities and on-target toxicities mediated by a TRAIL receptor agonist following cotreatment with panobinostat.

Author: MartinBen P, FrewAilsa J, BotsMichael, FoxStephen, LongFenella, TakedaKazuyoshi, YagitaHideo, AtadjaPeter, SmythMark J, JohnstoneRicky W

Tumor cell apoptosis
Tumor eradication
Fatal outcomes
Gastrointestinal toxicity

The HDAC inhibitor panobinostat can sensitize tumor cells to apoptosis mediated by the anti-mouse TRAIL receptor antibody MD5-1. This combination was effective in eradicating tumors in mice, but it also caused fatal gastrointestinal toxicities.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Histone Deacetylase Inhibitors Inhibit Rhabdomyosarcoma by Reactive Oxygen Species-Dependent Targeting of Specificity Protein Transcription Factors.

Author: HedrickErik, CroseLisa, LinardicCorinne M, SafeStephen

Apoptosis induction
Invasion inhibition
RMS tumor growth inhibition

Panobinostat and vorinostat are histone deacetylase inhibitors. This study demonstrated the efficacy of panobinostat and vorinostat in inhibiting rhabdomyosarcoma tumor growth in vivo and inducing apoptosis in RMS cell lines. These effects were found to be due to epigenetic repression of cMyc and independent of histone acetylation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Optimizing current and emerging therapies in multiple myeloma: a guide for the hematologist.

Author: RazaShahzad, SafyanRachael A, RosenbaumEvan, BowmanAlex S, LentzschSuzanne

Improved overall survival
Improved response rates

This review outlines the current therapeutic approach to the management of multiple myeloma (MM). It highlights the advancements in treatment options, including proteasome inhibitors and immunomodulatory drugs, and emphasizes the importance of risk stratification, management of comorbidities, and treatment side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

12.

EMA Review of Panobinostat (Farydak) for the Treatment of Adult Patients with Relapsed and/or Refractory Multiple Myeloma.

Author: TzoganiKyriaki, van HennikPaula, WalshIta, De GraeffPieter, FolinAnnika, SjöbergJan, SalmonsonTomas, BerghJonas, LaaneEdward, LudwigHeinz, GisselbrechtChristian, PignattiFrancesco

Multiple myeloma treatment
Anemia
Diarrhea
Fatigue
Lymphopenia
Nausea
Neutropenia
Thrombocytopenia
Vomiting

Panobinostat, in combination with bortezomib and dexamethasone, was approved for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens. Panobinostat is an orally available HDAC inhibitor that increases histone acetylation, leading to transcriptional activation. The combination showed a significant difference in progression-free survival compared to placebo, but it also had common side effects such as diarrhea, fatigue, and thrombocytopenia.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

13.

Clinical use and applications of histone deacetylase inhibitors in multiple myeloma.

Author: TandonNidhi, RamakrishnanVijay, KumarShaji K

Improved MM survival
New MM therapies
HDACi side effects

Histone deacetylase inhibitors (HDACi) have shown promising results in treating multiple myeloma, especially in combination with other therapies.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

Safety issues and management of toxicities associated with new treatments for multiple myeloma.

Author: BrioliAnnamaria, MüggeLars-Olof, HochhausAndreas, Von Lilienfeld-ToalMarie

Improved outcomes
Adverse events

New drugs for multiple myeloma (MM) have significantly improved patient outcomes, but have also introduced a new range of adverse events. Four novel agents, carfilzomib, elotuzumab, daratumumab, and panobinostat, have been approved for MM treatment. This review provides guidance to physicians for recognizing and managing toxicities associated with these new therapies.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

16.

Diarrhea in Multiple Myeloma: A Review of the Literature.

Author: FaimanBeth

Chemotherapy
Diarrhea
Disease progression
Quality of life

This article discusses diarrhea, a common and inadequately managed symptom that patients with multiple myeloma (MM) experience as a result of cancer treatment. Diarrhea in patients with MM often is severe enough to warrant dose reduction, delays, or discontinuation of chemotherapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

18.

Efficacy and Safety of Panobinostat in Relapsed or/and Refractory Multiple Myeloma: Meta Analyses of Clinical Trials and Systematic Review.

Author: LiuJing-di, SunChun-Yan, TangLiang, WuYing-Ying, WangQing-Yun, HuBei, HuYu

Multiple myeloma treatment
Anemia
Diarrhea
Fatigue
Lymphopenia
Nausea
Neutropenia
Thrombocytopenia

This systematic literature review assessed the efficacy and safety of panobinostat for patients with relapsed or/and refractory multiple myeloma (MM). The study found that panobinostat combined with other agents had an overall response rate of 0.45 and was well tolerated.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

21.

Histone deacetylase inhibitor panobinostat in combination with rapamycin confers enhanced efficacy against triple-negative breast cancer.

Author: WuKunlin, ZhangHuihao, ZhouLinlin, ChenLing, MoCaiqin, XuSunwang, LinJunyu, KongLingjun, ChenXiangjin

PANO/RAPA combination
TNBC treatment

A combination of panobinostat, a histone deacetylase inhibitor, and rapamycin, an mTOR inhibitor, shows promising anticancer effects against triple-negative breast cancer (TNBC) in both cell culture and mouse models. The combination was more effective than monotherapy in reducing tumor growth and inducing apoptosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

Novel α,β-unsaturated hydroxamic acid derivatives overcome cisplatin resistance.

Author: PfliegerMarc, HamacherAlexandra, ÖzTaner, Horstick-MucheNadine, BoesenBenedikt, SchrenkChristian, KassackMatthias U, KurzThomas

Cancer cell proliferation inhibition
Cisplatin resistance overcoming
HDAC inhibition

Two novel HDAC inhibitors (HDACi), 6e and 7j, demonstrated potent HDAC inhibitory activity and inhibition of proliferation against human cancer cell lines. They enhanced cisplatin-induced cytotoxicity and showed synergistic interactions with cisplatin, particularly in cisplatin-resistant cells. These findings suggest that dual class I/HDAC6 inhibitors may be a promising option for overcoming cisplatin resistance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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