Side Effects of bortezomib: A Synthesis of Findings from 29 Studies

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Original Abstract of the Article

Key research findings

Bortezomib is a proteasome inhibitor commonly used to treat multiple myeloma and other cancers. 18 . While it has shown effectiveness in treating cancer, it can cause a range of side effects, primarily affecting the nervous system, cardiovascular system, and skin. 12 , 13 , 14 .

Bortezomib works by inhibiting the proteasome, a cellular machine responsible for breaking down proteins. This disruption can impact both cancerous and healthy cells, potentially leading to adverse effects. 16 .

Researchers are actively exploring strategies to minimize bortezomib's side effects. One promising approach involves targeted delivery of bortezomib to bone tumors using bisphosphonates, which bind to bone tissue. This method aims to concentrate the drug at the tumor site while reducing systemic exposure and its associated side effects. 25 .

Reasons for side effects

Bortezomib disrupts the normal function of proteasomes, which are critical for protein degradation within cells. This disruption can lead to a buildup of proteins, potentially causing damage to various cells and tissues, resulting in side effects. For instance, the accumulation of proteins in nerve cells could contribute to neurotoxicity.

Common side effects

Neurotoxicity

Peripheral neuropathy is a common side effect of bortezomib. 12 , 23 . It manifests as numbness or pain in the hands and feet. The severity of peripheral neuropathy can vary depending on the dosage and duration of bortezomib treatment, as well as individual factors like age and pre-existing conditions. 12 .

Cardiotoxicity

Bortezomib can also affect the heart, potentially leading to heart failure. 19 . The risk of heart toxicity can increase with prolonged treatment or higher dosages. 12 .

Skin toxicity

Bortezomib can cause skin reactions, including rashes and, in rare cases, Stevens-Johnson syndrome. 13 . The severity of these reactions can vary depending on individual sensitivity and treatment factors.

Others

Bortezomib can cause other side effects, including gastrointestinal problems and low platelet counts. 12 . The likelihood and severity of these side effects can vary between individuals.

Countermeasures against side effects

Neurotoxicity

Strategies to mitigate peripheral neuropathy include administering neuroprotective agents and adjusting the dosage and duration of bortezomib therapy. 12 .

Cardiotoxicity

Managing cardiotoxicity may involve using medications that reduce the strain on the heart and adjusting bortezomib dosages. 19 .

Skin toxicity

Skin reactions can be addressed by using anti-inflammatory medications like steroids and by adjusting bortezomib dosages. 13 .

Comparison between studies

Common points of studies

Multiple research studies have consistently indicated that bortezomib can cause side effects such as neurotoxicity, cardiotoxicity, and skin toxicity. 12 , 13 , 14 .

Differences in studies

There are differences in the incidence and severity of bortezomib's side effects between studies. This variation may be attributed to factors such as differences in patient populations, dosages of bortezomib, and the duration of treatment.

Precautions for applying research to real life

While bortezomib can be an effective cancer treatment, it's important to remember that it carries risks of side effects. 12 , 13 , 14 . When considering bortezomib therapy, carefully weigh the potential benefits against the risks and discuss these considerations with your healthcare provider.

Limitations of current research

The research on bortezomib's side effects is still ongoing. More studies are needed to fully understand the long-term effects of prolonged bortezomib use, especially the impact on various organs and systems.

Future research directions needed

Continued research on bortezomib's side effects is crucial. This includes developing new therapies to mitigate side effects, exploring alternative drug delivery methods, and conducting long-term studies to assess the long-term consequences of bortezomib use.

Conclusion

Bortezomib is an important tool in cancer treatment, but its side effects should not be overlooked. Understanding the potential risks and benefits associated with this drug is essential for making informed decisions about treatment options. Ongoing research continues to shed light on the mechanisms and management of bortezomib's side effects, ultimately aiming to improve patient care and minimize adverse outcomes.

Literature analysis of 29 papers
Positive Content
22
Neutral Content
0
Negative Content
7
Article Type
0
1
2
9
26
1.

The Potential Role of Proinflammatory Cytokines and Complement Components in the Development of Drug-Induced Neuropathy in Patients with Multiple Myeloma.

Author: ŁuczkowskaKarolina, RutkaMagdalena, RogińskaDorota, PaczkowskaEdyta, BaumertBartłomiej, MilczarekSławomir, GórskaMartyna, KuligPiotr, OsękowskaBogumiła, JanowskiMichał, SafranowKrzysztof, SommerfeldKrzysztof, BorowieckaEwa, ZawodnyPiotr, KoclęgaAnna, HelbigGrzegorz, MachalińskiBogusław

MM drug neuropathy

This study investigated the potential link between proinflammatory factors and the development of peripheral neuropathy (PN) in multiple myeloma (MM) patients receiving VTD treatment. The study found that increased levels of CCL2, IL-1β, and IFN-γ in plasma were associated with PN. The study suggests that targeting these inflammatory factors could help prevent PN in MM patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Clinical Experience of Proteasome Inhibitor Bortezomib Regarding Efficacy and Safety in Severe Systemic Lupus Erythematosus: A Nationwide Study.

Author: WalhelmTomas, GunnarssonIva, HeijkeRebecca, LeonardDag, TrysbergEstelle, ErikssonPer, SjöwallChristopher

BTZ efficacy
Reduced proteinuria
SLE treatment
Hypogammaglobinemia
Infections

This study investigated the efficacy and safety of bortezomib (BTZ) in patients with advanced systematic lupus erythematosus (SLE) who were unresponsive to conventional immunosuppressive therapies. The results showed that BTZ, when combined with corticosteroids, significantly reduced global disease activity and proteinuria. While BTZ was generally well-tolerated, common side effects included infections.

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.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Bortezomib in anti-N-Methyl-d-Aspartate-Receptor (NMDA-R) encephalitis: A systematic review.

Author: DinotoAlessandro, CheliMarta, BratinaAlessio, SartoriArianna, ManganottiPaolo

NMDAR encephalitis treatment
Side effects

Bortezomib, a proteasome inhibitor, has a promising role in treating N-methyl-d-aspartate receptor (NMDAR) encephalitis, a potentially treatable condition. A literature review found that bortezomib improved outcomes in 55.2% of patients but caused side effects in 37.9%.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

5.

Targeting Ubiquitin-Proteasome System With Copper Complexes for Cancer Therapy.

Author: ChenXin, DouQ Ping, LiuJinbao, TangDaolin

Cancer treatment
Drug resistance
Drug-drug interactions
Side effects

This review summarizes the functions and applications of copper complexes as inhibitors of the ubiquitin-proteasome system (UPS) in cancer treatment. Copper complexes can inhibit key components of the UPS, suggesting their potential as novel anticancer agents.

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.

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial.

Author: ClavoBernardino, Martínez-SánchezGregorio, Rodríguez-EsparragónFrancisco, Rodríguez-AbreuDelvys, GalvánSaray, Aguiar-BujandaDavid, Díaz-GarridoJuan A, CañasSilvia, Torres-MataLaura B, FabeloHimar, TéllezTeresa, Santana-RodríguezNorberto, Fernández-PérezLeandro, Marrero-CallicoGustavo

Potential for CIPN management
CIPN

Ozone therapy has the potential to prevent or improve chemotherapy-induced peripheral neuropathy (CIPN). Although no clinically relevant approaches for the prevention and treatment of CIPN currently exist, ozone therapy can induce an adaptive antioxidant and anti-inflammatory response, which could be potentially useful in the management of CIPN. Randomized controlled trials are ongoing.

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

8.

Role of HMGB1 in Chemotherapy-Induced Peripheral Neuropathy.

Author: SekiguchiFumiko, KawabataAtsufumi

CIPN prevention

This review focuses on the role of high mobility group box 1 (HMGB1) in chemotherapy-induced peripheral neuropathy (CIPN). HMGB1, a pro-nociceptive mediator released extracellularly, plays a key role in CIPN development. Soluble thrombomodulin (TMα) degrades HMGB1 and shows potential for CIPN prevention.

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

9.

Non-Hematologic Toxicity of Bortezomib in Multiple Myeloma: The Neuromuscular and Cardiovascular Adverse Effects.

Author: PancheriElia, GuglielmiValeria, WilczynskiGrzegorz M, MalatestaManuela, ToninPaola, TomelleriGiuliano, NowisDominika, VattemiGaetano

MM treatment
Cardiovascular toxicity
Neuromuscular toxicity

The study reviews the neuromuscular and cardiovascular side effects of bortezomib, a proteasome inhibitor used in the treatment of multiple myeloma (MM), focusing on the molecular mechanisms underlying its toxicity.

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

10.

Alpha-lipoic acid alters the antitumor effect of bortezomib in melanoma cells in vitro.

Author: TakácsAngéla, LajkóEszter, LángOrsolya, IstenesIldikó, KőhidaiLászló

Antitumor effect
Neuropathy

This study investigates the impact of antioxidants, alpha-lipoic acid and vitamin B1, on the antitumor activity of bortezomib, a proteasome inhibitor used in cancer treatment.

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

11.

Targeting anti-cancer agents to bone using bisphosphonates.

Author: XingLianping, EbetinoFrank H, BoeckmanRobert K, SrinivasanVenkat, TaoJianguo, SawyerTomi K, LiJinbo, YaoZhenqiang, BoyceBrendan F

Bisphosphonate conjugation
Bone disease treatment
Targeted drug delivery

Bone tumors can weaken bones and increase the risk of fractures. This review discusses the use of bisphosphonates, a class of drugs that target bone, as a way to deliver cancer drugs directly to the tumor site. This approach has shown promising results in preclinical and early clinical trials, demonstrating the potential to improve drug efficacy and reduce side effects.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

13.

A case of bortezomib (Velcade)-induced Stevens-Johnson syndrome confirmed by patch test.

Author: ChoiGil-Soon, LeeHo Sup, KimHee-Kyoo

Stevens-Johnson syndrome

Bortezomib, a proteasome inhibitor, is a standard of care for multiple myeloma, but can rarely cause severe cutaneous adverse reactions such as Stevens-Johnson syndrome. A case of bortezomib-induced SJS confirmed by patch test is reported.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

14.

Bortezomib induced pulmonary toxicity: a case report and review of the literature.

Author: SaglamBurcin, KalyonHakan, OzbalakMurat, OrnekSerdar, KeskeSiran, TabakLevent, CakarNahit, ZerenHandan, AytekinSaide, BolukbasiYasemin, FerhanogluBurhan

Multiple myeloma treatment
Lung injury

This case report highlights the rare but potentially fatal adverse effect of Bortezomib-induced lung injury in a patient with multiple myeloma. This emphasizes the importance of monitoring for pulmonary complications in patients receiving Bortezomib therapy.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

15.

The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells.

Author: TakácsAngéla, SzászZsófia, KalabayMárton, BárányPéter, CsámpaiAntal, HegyesiHargita, LángOrsolya, LajkóEszter, KőhidaiLászló

Improved efficacy
Reduced side effects

Combining bortezomib (BOZ) and a TRAIL-inducing compound (TIC10) demonstrated synergistic antitumor effects in A2058 melanoma cells, potentially allowing for reduced BOZ doses and reduced side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

16.

Effects of bortezomib on mouse preimplantation embryo development in vitro.

Author: CobanCennet Sinem, MutluayDuygu

Fetal harm

This study discusses the potential side effects of bortezomib, a proteasome inhibitor used in cancer therapy, during preimplantation embryo development.

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

17.

Fabry disease associated with multiple myeloma: a case report.

Author: AdachiKeika, TokuyamaHirobumi, OshimaYoichi, ItohTomoaki, HashiguchiAkinori, YamakawaHiroyuki, TogawaTadayasu, SakurabaHitoshi, WakinoShu, ItohHiroshi

Improves renal function
Treats Fabry disease

This case report describes a 68-year-old woman diagnosed with both Fabry disease (FD) and multiple myeloma (MM). The patient's renal pathology showed features consistent with both conditions, highlighting the importance of considering FD in MM patients with multiple organ abnormalities or familial history.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

Bortezomib-loaded lipidic-nano drug delivery systems; formulation, therapeutic efficacy, and pharmacokinetics.

Author: MahmoudianMohammad, ValizadehHadi, LöbenbergRaimar, Zakeri-MilaniParvin

Improves therapeutic aspect
Reduces side effects

Lipid-based nanodrug delivery systems (LNDDSs) offer the potential to reduce side effects and improve the therapeutic aspect of Bortezomib (BTZ), a proteasome inhibitor used for treating multiple myeloma and mantle cell lymphoma.

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

20.

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

Author: DasBhaskar C, NandwanaNitesh K, DasSasmita, NandwanaVarsha, ShareefMohammed Adil, DasYogarupa, SaitoMariko, WeissLouis M, AlmaguelFrankis, HosmaneNarayan S, EvansTodd

Boron-based drug candidates

This review summarizes boron-containing drug candidates for various diseases, highlighting their synthesis, structure-activity relationships, and biological activities.

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

21.

Evaluation of a Generic Bortezomib Molecule in Newly Diagnosed Multiple Myeloma Patients

Author: MersinSinan, GedükAyfer, MehtapÖzgür, TarkunPınar, ÜnalSerkan, PolatMerve Gökçen, AygünKemal, YenihayatEmel Merve, AlbayrakHayrunnisa, HacıhanifioğluAbdullah

Effectiveness
Reliability
Side effects

Generic bortezomib, a widely used drug for treating multiple myeloma, has shown comparable effectiveness and safety profiles to its branded counterpart in newly diagnosed patients. This study suggests that generic bortezomib provides a reliable and cost-effective treatment option for multiple myeloma.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

Pharmacodynamic, pharmacokinetic, and phase 1a study of bisthianostat, a novel histone deacetylase inhibitor, for the treatment of relapsed or refractory multiple myeloma.

Author: ZhouYu-Bo, ZhangYang-Ming, HuangHong-Hui, ShenLi-Jing, HanXiao-Feng, HuXiao-Bei, YuSong-da, GaoAn-Hui, ShengLi, SuMing-Bo, WeiXiao-Li, ZhangYue, ZhangYi-Fan, GaoZhi-Wei, ChenXiao-Yan, NanFa-Jun, LiJia, HouJian

MM treatment

Bisthianostat, a novel HDAC inhibitor, showed antitumor activity in multiple myeloma (MM) cells in vitro and in vivo. Bisthianostat combined with bortezomib displayed synergistic antitumor effects. Bisthianostat was well-tolerated in a phase 1a study with no grade 3/4 nonhematological adverse events. These findings support further clinical trials of bisthianostat in MM.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

23.

Mechanisms and Potential Treatment Options of Heart Failure in Patients With Multiple Myeloma.

Author: ProskuriakovaEkaterina, JadaKeji, Kakieu DjossiSandrine, KhedrAnwar, NeupaneBandana, MostafaJihan A

Cardioprotection
Improved survival
Heart failure

Multiple myeloma, a cancer of plasma cells, often leads to heart failure as a side effect of treatment. Cardiac amyloidosis can also cause heart failure. This article discusses the molecular mechanisms of heart failure in multiple myeloma patients, including doxorubicin cardiotoxicity and proteasome inhibitors' effects. Potential treatment options, such as liposomal doxorubicin, mitochondrial biogenesis enhancers, and cardioprotective agents, are explored.

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

24.

The Sec61 translocon is a therapeutic vulnerability in multiple myeloma.

Author: DomengerAntoine, ChoisyCaroline, BaronLudivine, MayauVéronique, PerthameEmeline, DerianoLudovic, ArnulfBertrand, BoriesJean-Christophe, DadaglioGilles, DemangelCaroline

MM cell death
Drug resistance

This study investigated the use of mycolactone, a Sec61 inhibitor, for the treatment of multiple myeloma (MM). Mycolactone effectively disrupted MM proteostasis, leading to cell death and overcoming drug resistance. A combination of mycolactone and bortezomib showed superior therapeutic efficacy over single-drug treatments in immunodeficient mice engrafted with MM cells.

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

25.

Bone-Targeted Bortezomib Inhibits Bortezomib-Resistant Multiple Myeloma in Mice by Providing Higher Levels of Bortezomib in Bone.

Author: TaoJianguo, SrinivasanVenkat, YiXiangjiao, ZhaoYingchun, ZhangHengwei, LinXi, ZhouXichao, BoyceBrendan F, VillaltaPeter W, EbetinoFrank H, HoKoc Kan, BoeckmanRobert K, XingLianping

MM treatment
Reduced bone destruction
Reduced metastasis
Reduced tumor burden
Neurotoxicity
Thrombocytopenia

Bone-targeted conjugate (BP-Btz) was developed to deliver bortezomib (Btz) to bone for treating multiple myeloma (MM). BP-Btz overcomes Btz resistance, reduces tumor burden, and prevents bone destruction and metastasis in mice. It has a longer half-life and higher local concentration in bone compared to Btz.

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

26.

Real-world evidence of levofloxacin prophylaxis in elderly patients with newly diagnosed multiple myeloma who received bortezomib, melphalan, and prednisone regimen.

Author: KimSu-In, JungSung-Hoon, YhimHo-Young, JoJae-Cheol, SongGa-Young, KimMihee, AhnSeo-Yeon, AhnJae-Sook, YangDeok-Hwan, KimHyeoung-Joon, LeeJe-Jung

Infection prevention
MM treatment

This study evaluated the efficacy of levofloxacin prophylaxis in elderly patients with newly diagnosed multiple myeloma (MM) receiving bortezomib, melphalan, and prednisone (VMP) therapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

27.

Comprehensive Analysis of Bortezomib-Induced Adverse Events Using the Japanese Real-World Database.

Author: SatokiAya, UchidaMayako, FujiwaraMasaki, UesawaYoshihiro, ShimizuTadashi

PN risk
TLS risk

Bortezomib, a first-line therapy for multiple myeloma, is associated with a higher incidence of peripheral neuropathy (PN) and tumor lysis syndrome (TLS) compared to other drugs. A comprehensive assessment of bortezomib's safety profile is needed.

NewsMedia reports that provide information on the latest events and information. Newspapers, television, and the Internet are the main media.

Language : English

28.

Impact of Concomitant Use of Azoles on Bortezomib-related Adverse Drug Reactions Using JADER.

Author: ImatohTakuya, MatsumotoTaichi, HaramakiYutaka, MigitaKeisuke

Adverse drug events

This study investigated the impact of azoles, antifungal drugs, on bortezomib-related adverse reactions in patients with hematologic malignancies using a pharmacoepidemiological approach.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

29.

Lipid Prodrug Nanoassemblies via Dynamic Covalent Boronates.

Author: DingYuxun, HuXiaowen, PiaoYinzi, HuangRong, XieLingping, YanXiaojian, SunHui, LiYuanfeng, ShiLinqi, LiuYong

Minimized side effects
Targeted drug release

This study introduces a novel method to create lipid prodrug nanoassemblies (LPNAs) using dynamic covalent boronate chemistry. The resulting LPNAs possess unique properties like dynamic drug loading, charge reversal, and targeted release, demonstrating enhanced therapeutic efficacy compared to free drugs in vitro and in vivo.

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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