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Proposal for a preventive protocol for medication-related osteonecrosis of the jaw.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some patients exposed to certain drugs (antiresorptives such as bisphosphonates or denosumab, and antiangiogenic drugs). From a review of the literature it appears that there is no uniform criterion when selecting preventive measures; these vary according to author. Likewise, the measures recommended are usually general, so that in few cases they result in specific actions to be applied depending on the different variables involved such as the type of drug used, the duration of its appli

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… On the other hand, both the antiangiogenic drugs such as Bevacizumab or Sunitinib, and some bisphosphonates such as zoledronic acid are capable of inhibiting angiogenesis, by reducing the formation of blood vessels, which is fundamental for healing and bone remodelling ( 4 ). … Acid” OR “Alendronate” OR “Etidronic Acid” OR “Etidronate” OR “Ibandronic Acid” OR “Ibandronate” OR “Pamidronate” OR “Risedronic Acid” OR “Risedronate” OR “Zoledronic Acid” OR “Zoledronate” OR “Denosumab” OR “Human monoclonal antibody to RANKL” OR “RANK ligand” OR “RANK antibody” OR “Bevacizumab” or “Sunitinib …

Combined Administration of Bisphosphonates, Chemotherapeutic Agents, and/or Targeted Drugs Increases the Risk for Stage 3 Medication-Related Osteonecrosis of the Jaw: A 4-Year Retrospective Study.

OBJECTIVES: Patients with stage 3 medication-related osteonecrosis of the jaw (MRONJ) suffer from severe complications. Chemotherapeutic agents and targeted drugs are considered to be associated with the development of MRONJ. However, little is known regarding the association of those agents with stage 3 MRONJ. The purpose of this study is to analyze the comprehensive medication history of patients with advanced-stage MRONJ (stage 2 and stage 3) and evaluate the possible risk factors for stage 3 MRONJ. Patients and Methods. Sixty patients with advanced-stage MRONJ were involved in this retrosp

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… | 0 | 2 (9.2) | 9.5 ± 7.5 | Erlotinib | 1 (7.7) | 50.0 | 0 | 0 | Icotinib | 3 (23.1) | 30.0 ± 6.5 | 2 (9.2) | 28.0 ± 7.0 | Bevacizumab | 1 (7.7) | 24.0 | 2 (9.2) | 22.0 ± 10.0 | Gefitinib | 3 (23.1) | 10.0 ± 2.0 | 5 (22.7) | 40.3 ± 25.7 | Osimertinib | 1 (7.7) | 6.0 | 3 (13.6) | 12.0 ± 3.0 | Sunitinib … Targeted drugs, including sunitinib, erlotinib, gefitinib, icotinib, and apatinib, act as tyrosine kinase inhibitors (TKIs) which work on the epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) receptor [ 25 , 26 ]. …

mTOR Cross-Talk in Cancer and Potential for Combination Therapy.

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understandi

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… In the retrospective analysis of a randomized trial comparing everolimus with a VEGF Receptor (VEGFR)-Tyrosine Kinase Inhibitor (TKI) (sunitinib) as first-line treatment for mRCC (RECORD-3 trial), Protein PolyBroMo-1 ( PBRM1 ) and BAP1 mutations were associated with significantly longer (median 12.8 …

Guidelines for treatment of renal injury during cancer chemotherapy 2016.

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… ifosfamide, azacitidine, imatinib, pamidronate Magnesium wasting cisplatin, anti-EGFR monoclonal antibodies Nephrogenic diabetes insipidus cisplatin, ifosfamide, pemetrexed Syndrome of inappropriate antidiuretic hormone secretion cyclophosphamide, vincristine Acute interstitial nephritis sorafenib, sunitinib … ifosfamide, azacitidine, imatinib, pamidronate Magnesium wasting | cisplatin, anti-EGFR monoclonal antibodies Nephrogenic diabetes insipidus | cisplatin, ifosfamide, pemetrexed Syndrome of inappropriate antidiuretic hormone secretion | cyclophosphamide, vincristine Acute interstitial nephritis | sorafenib, sunitinib …

Cancer therapy-associated Takotsubo cardiomyopathy: A narrative review of mechanisms, drug associations, and clinical implications.

Anticancer therapies have been increasingly associated with Takotsubo cardiomyopathy (TTC). As prior reports remain fragmented across case studies and drug-specific reviews, this paper offers one of the most comprehensive reviews to date of cancer therapy-associated TTC. While classically triggered by emotional or physical stress, TTC has been increasingly associated with chemotherapy and other cancer-directed therapies. This literature review explores the pathophysiology, clinical features, and evolving evidence linking anticancer agents to TTC, with a focus on cytotoxic cancer therapy, hormo

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… VEGF pathway inhibitors (bevacizumab, axitinib, sunitinib) and EGFR inhibitors (afatinib, osimertinib) may promote TTC via microvascular injury, endothelial dysfunction, or autonomic imbalance, mechanisms that align closely with TTC's established pathophysiologic triggers [22] , [48] , [49] , [50] , … Mitochondrial oxidative stress plays a critical role in the cardiotoxicity of sunitinib: running title: Sunitinib and oxidative stress in hearts. Toxicology. 2019;426 doi: 10.1016/j.tox.2019.152281. 60. Sun H., Ji Y., Li S., Dong H. …

Therapeutic biomarkers in acute myeloid leukemia: functional and genomic approaches.

Acute myeloid leukemia (AML) is clinically and genetically a heterogeneous disease characterized by clonal expansion of abnormal hematopoietic progenitors. Genomic approaches to precision medicine have been implemented to direct targeted therapy for subgroups of AML patients, for instance, IDH inhibitors for IDH1/2 mutated patients, and FLT3 inhibitors with FLT3 mutated patients. While next generation sequencing for genetic mutations has improved treatment outcomes, only a fraction of AML patients benefit due to the low prevalence of actionable targets. In recent years, the adoption of newer f

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… Based on the specific criteria devised in the study, four major drugs (venetoclax, BCL2i; sunitinib, VEGFR/FLT3i; dasatinib, BCR-ABL1/other kinases inhibitor, and temsirolimus mTORi) were tested for the clinical implementation of the FPMTB data. … A phase I/II study of sunitinib and intensive chemotherapy in patients over 60 years of age with acute myeloid leukaemia and activating FLT3 mutations . Br J Haematol ( 2015 ) 169 : 694–700 . doi: 10.1111/BJH.13353 25818407 70 Röllig C Serve H Hüttmann A Noppeney R Müller-Tidow C Krug U . …

Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer.

BackgroundThe overwhelming majority of dose-escalation clinical trials use methods that seek a maximum tolerable dose, including rule-based methods like the 3+3, and model-based methods like CRM and EWOC. These methods assume that the incidences of efficacy and toxicity always increase as dose is increased. This assumption is widely accepted with cytotoxic therapies. In recent decades, however, the search for novel cancer treatments has broadened, increasingly focusing on inhibitors and antibodies. The rationale that higher doses are always associated with superior efficacy is less clear for t

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… A phase 1 bayesian dose selection study of bortezomib and sunitinib in patients with refractory solid tumor malignancies. Br J Cancer. 2013;108(4):762–5. doi: 10.1038/bjc.2012.604. 48. … Sunitinib in combination with gemcitabine for advanced solid tumours: a phase i dose-finding study. Br J Cancer. 2013;108(7):1393–401. doi: 10.1038/bjc.2013.96. 126. …

Guidance for the prevention and treatment of cancer-associated venous thromboembolism.

Venous thromboembolism (VTE) is a highly prevalent complication of malignancy with emerging changes in incidence, diagnosis and treatment paradigms. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. We address a) the appropriate workup to search for occult malignancy in patients with idiopathic VTE, b) identification of high-risk cancer patients for primary thromboprophylaxis, c) the appropriate immediate and long-term treatment for people with cancer diagnosed with acute t

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… Indeed, drugs targeting angiogenesis such as bevacizumab, sunitinib, sorafenib, the multi-targeted tyrosine kinase inhibitor ponatinib and the immunomodulator lenalidomide have been associated with arterial thromboembolism [ 18 , 19 ], immunomodulatory agents such as thalidomide and lenalidomide have … Choueiri TK Schutz FA Je Y Rosenberg JE Bellmunt J Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials J Clin Oncol 2010 28 13 2280 2285 10.1200/JCO.2009.27.2757 20351323 20. …

Cancer-Therapy-Related Cardiac Dysfunction: Latest Advances in Prevention and Treatment.

The increasing efficacy of cancer therapies has significantly improved survival rates, but it has also highlighted the prevalence of cancer-therapy-related cardiac dysfunction (CTRCD). This review provides a comprehensive overview of the identification, monitoring, and management of CTRCD, a condition resulting from several treatments, such as anthracyclines, HER2-targeted therapies, target therapies, and radiotherapy. The paper includes a discussion of the mechanisms of CTRCD associated with various cancer treatments. Early detection through serum biomarkers and advanced imaging techniques is

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… In particular, in patients treated with sunitinib, reduced CFR in the LAD coronary artery is an early marker of cardiotoxicity and correlates inversely with treatment duration and inflammation markers [ 36 , 42 ]. … Impaired coronary flow reserve in metastatic cancer patients treated with sunitinib. J. BUON. 2013;18:775–781. doi: 10.1200/jco.2011.29.15_suppl.e15136. 43. Ferrara F., Capuano F., Cocchia R., Ranieri B., Contaldi C., Lacava G., Capone V., Chianese S., Rega S., Annunziata R., et al. …

Ocular Surface Side Effects of Novel Anticancer Drugs.

Surgery, anticancer drugs (chemotherapy, hormonal medicines, and targeted treatments), and/or radiation are common treatment strategies for neoplastic diseases. Anticancer drugs eliminate malignant cells through the inhibition of specific pathways that contribute to the formation and development of cancer. Given the ability of such pharmacological medications to combat cancerous cells, their role in the management of neoplastic diseases has become essential. However, these drugs may also lead to undesirable systemic and ocular adverse effects due to cyto/neuro-toxicity and inflammatory reactio

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… Several cases of superficial ocular anterior toxicity and blurred vision were reported after the administration of sunitinib and sorafenib. … Indeed, to limit the pathological pathway activation in several cancers, some VEGF and VEGF receptor (VEGFR) inhibitors have been developed, including sorafenib, sunitinib, vandetanib, lenvatinib, axitinib, bevacizumab, ramucirumab, cabozantinib, and pazopanib [ 13 ]. …

Update on current diagnosis and management of anaplastic thyroid carcinoma.

Well-differentiated thyroid carcinoma has a favorable prognosis with a 5-year survival rate of over 95%. However, the undifferentiated or anaplastic type accounting for < 0.2%, usually in elderly individuals, exhibits a dismal prognosis with rapid growth and disappointing outcomes. It is the most aggressive form of thyroid carcinoma, with a median survival of 5 mo and poor quality of life (airway obstruction, dysphagia, hoarseness, persistent pain). Early diagnosis and staging are crucial. Diagnostic tools include biopsy (fine needle aspiration, core needle, open surgery), high-resolution ultr

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… Likewise, sorafenib had limited usefulness; instead, other anti-angiogenetic agents, such as vandetanib, sunitinib, and lenvatinib, exhibited significant anti-neoplastic efficacy[ 24 ]. … Sunitinib, another multitarget tyrosine inhibitor, acts mainly against VEGFR and PDGFR to inhibit tumor growth by deprivation of its blood supply[ 62 ]. …

Tips and Tricks and Clinical Outcome of Cryopreserved Human Amniotic Membrane Application for the Management of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Pilot Study.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication of certain pharmacological treatments such as bisphosphonates, denosumab, and angiogenesis inhibitors. There are currently no guidelines on its management, particularly in advanced stages. The human amniotic membrane (hAM) has low immunogenicity and exerts anti-inflammatory, antifibrotic, antimicrobial, antiviral, and analgesic effects. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with suitable mechanical properties (permeability, stability, elasticity, flex

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… Medication-related osteonecrosis of the jaw (MRONJ) is a complication caused by various treatments including bone antiresorptive agents (bisphosphonates and denosumab) and angiogenesis inhibitors (sunitinib, bevacizumab, among others). … As seen in Table 1 , patient 1 (P1) suffered from renal cancer and was treated with subcutaneous denosumab and oral sunitinib; P2, P4, P5, and P6 suffered from breast cancer and were treated with IV bisphosphonates and subcutaneous denosumab or subcutaneous denosumab alone; P3 suffered from prostate …

Combination of CTLA-4 and PD-1 blockers for treatment of cancer.

Targeting checkpoints of immune cell activation has been demonstrated to be the most effective approach for activation of anti-tumor immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), both inhibitory checkpoints commonly seen on activated T-cells have been found to be the most reliable targets for the treatment of cancer. Six drugs targeting PD-1 or its ligand PD-L1 and one drug targeting CTLA-4 have been approved for treatment of different types of cancers and several others are in advanced stages of development. The drugs when a

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… Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018;378(14):1277–1290. doi: 10.1056/NEJMoa1712126. 100. Cella D, Grunwald V, Escudier B, Hammers HJ, George S, Nathan P, et al. … Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial. Lancet Oncol. 2019;20(2):297–310. doi: 10.1016/S1470-2045(18)30778-2. 101. …

γδ T Cell Immunotherapy-A Review.

Cancer immunotherapy utilizing Vγ9Vδ2 T cells has been developed over the past decade. A large number of clinical trials have been conducted on various types of solid tumors as well as hematological malignancies. Vγ9Vδ2 T cell-based immunotherapy can be classified into two categories based on the methods of activation and expansion of these cells. Although the in vivo expansion of Vγ9Vδ2 T cells by phosphoantigens or nitrogen-containing bisphosphonates (N-bis) has been translated to early-phase clinical trials, in which the safety of the treatment was confirmed, problems such as activation-ind

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… One patient received best supportive care and another three patients received anti-angiogenetic drugs (sorafenib, sunitinib, and sequential administration of sorafenib/sunitinib). The remaining five patients survived an average of 93 months following treatment. … Four of five patients received anti-angiogenetic drugs (sequential combinations of sorafenib, sunitinib, and axtinib). …

AI predictive modeling of survival outcomes for renal cancer patients undergoing targeted therapy.

Renal clear cell cancer (RCC) is a complex disease that is challenging to predict patient outcomes. Despite improvements with targeted therapy, personalized treatment planning is still needed. Artificial intelligence (AI) can help address this challenge by developing predictive models that accurately forecast patient survival periods. With AI-powered decision support, clinicians can provide patients with tailored treatment plans, enhancing treatment efficacy and quality of life. The study analyzed 267 patients with renal clear cell carcinoma, focusing on 26 who received targeted drug therapy.

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… Jin J Sunitinib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers Drug Resist. Updat 2023 67 100929 10.1016/j.drup.2023.100929 36739809 Jin, J. et al. Sunitinib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers. Drug Resist. …

Venetoclax Induces Cardiotoxicity through Modulation of Oxidative-Stress-Mediated Cardiac Inflammation and Apoptosis via NF-κB and BCL-2 Pathway.

Cardiovascular damage induced by anticancer therapy has become the main health problem after tumor elimination. Venetoclax (VTX) is a promising novel agent that has been proven to have a high efficacy in multiple hematological diseases, especially acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Considering its mechanism of action, the possibility that VTX may cause cardiotoxicity cannot be ruled out. Therefore, this study was designed to investigate the toxic effect of VTX on the heart. Male Sprague-Dawley rats were randomly divided into three groups: control, low-dose VTX

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… Changes in cardiac hypertrophic markers such as Bnp , α-Mhc, and β- Mhc have been found to be associated with cardiac toxicity, and were reported for several anticancer drugs, such as doxorubicin and sunitinib [ 28 , 29 ]. … Mitogen-Activated Protein Kinases Pathways Mediate the Sunitinib-Induced Hypertrophy in Rat Cardiomyocyte H9c2 Cells Cardiovasc. Toxicol. 2015 15 41 51 10.1007/s12012-014-9266-y 24984876 30. Ma W. Wei S. Zhang B. Li W. …

Stevens-Johnson syndrome/toxic epidermal necrolysis in patients treated with immune checkpoint inhibitors: A safety analysis of clinical trials and FDA pharmacovigilance database.

BackgroundThe association between immune checkpoint inhibitors (ICIs) and Stevens-Johnsons syndrome (SJS) /toxic epidermal necrolysis (TEN) is unclear. We assessed the risk of SJS and TEN related to ICIs, via a systematic analysis of SJS/TEN cases reported in clinical trials and the FDA Adverse Event Reporting System (FAERS).MethodsWe explored ICIs related SJS/TEN events in randomized control trials available in ClinicalTrials.gov and electronic databases (Pubmed, Embase, the Cochrane Central Register of Controlled Trials) up to 12 January 2021. Meta-analysis was performed by using Peto odds r

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… follow-up | Events reported NCT02576509 | Nivolumab | Hepatocellular Carcinoma | 84.9% | 367 | 63.9 (10.61) | 3.5y | ClinicalTrials.gov | Sorafenib | | | 363 | 64.5 (10.91) | | NCT02231749 | Nivolumab + Ipilimumab | Renal Cell Carcinoma | 73.7% | 547 | 61.1 (9.76) | 31m | ClinicalTrials.gov | Sunitinib … Chemotherapy | | | 171 | 60.5 (12.7) | | NCT02302807 | Atezolizumab 1200mg every 21d | Urothelial Bladder | 77.1% | 459 | 65.9 (9.6) | 46m | Powles 2018 | Chemotherapy | | | 443 | 66.1 (9.3) | | NCT02420821 | Atezolizumab + Bevacizumab | Renal Cell Carcinoma | 73.1% | | | | ClinicalTrials.gov | Sunitinib …

Optimizing Oral Targeted Anticancer Therapies Study for Patients With Solid Cancer: Protocol for a Randomized Controlled Medication Adherence Program Along With Systematic Collection and Modeling of Pharmacokinetic and Pharmacodynamic Data.

BackgroundThe strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response.ObjectiveThe aim o

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… Adherence was estimated for several classes of oral anticancer therapies (capecitabine, letrozole, exemestane, imatinib, sunitinib, and temozolomide). … Therapeutic drug monitoring of the new targeted anticancer agents imatinib, nilotinib, dasatinib, sunitinib, sorafenib and lapatinib by LC tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jul 15;877(22):1982–96. doi: 10.1016/j.jchromb.2009.04.045. 32. …

Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.

Tyrosine kinase inhibitor (TKI)-targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistan

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… ) | Treatment | References CML | BCR–ABL gene fusion | 100% of CML patients | First‐generation TKIs: imatinib Second‐generation TKIs: dasatinib, nilotinib, bosutinib Third‐generation TKIs: ponatinib (targeting T315I mutation) | 26 AML | FLT3 mutations | 30% of all AML cases | First‐generation TKIs: sunitinib … Patients receiving the combination regimen had a median PFS of 23.9 months compared with 9.2 months for those receiving sunitinib. …

Targeting cytokine and chemokine signaling pathways for cancer therapy.

Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles in both normal physiology and the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, and growth factors like TGF-β, VEGF, and EGF, can promote or inhibit tumor growth, influence the tumor microenvironment, and impact the efficacy of cancer treatments. Recent advances in targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate the immune system, inhibit tumor progression, and o