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DRUG:

zoledronic acid

i
Other names: CGP 42446, ZOL 446, CGP 42446A, AK-156
Company:
Generic mfg.
Drug class:
Bone resorption factor inhibitor, Osteoclast inhibitor
4d
Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors (clinicaltrials.gov)
P1/2, N=27, Not yet recruiting, University of Florida | Initiation date: Feb 2025 --> Jun 2025
Trial initiation date
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zoledronic acid
6d
New P4 trial
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zoledronic acid
7d
TOPAZ: Trial of Parkinson's and Zoledronic Acid (clinicaltrials.gov)
P4, N=2650, Active, not recruiting, California Pacific Medical Center Research Institute | Recruiting --> Active, not recruiting
Enrollment closed
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zoledronic acid
11d
Bisphosphonates in combination with alendronate sodium increase bone mineral density and modulate IL-6, TNF-α, and IGF-1 in patients with osteoporosis. (PubMed, Int J Clin Pharmacol Ther)
Zoledronic acid injection in combination with alendronate sodium increases the expression of IL-6, TNF-α, and IGF-I, suppresses bone resorption and promotes bone recovery in patients with osteoporosis.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IGF1 (Insulin-like growth factor 1)
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zoledronic acid
14d
Efficacy of natural killer T and gammadelta T cells in mesothelin-targeted immunotherapy of pancreatic cancer. (PubMed, Front Immunol)
In addition, the systemic administration of NKT and γδT cells activators, α-galactosylceramide (α-GalCer) and Zoledronate, could enhance the anti-tumor effect of MSLN/CD3 bsAb, with no apparent toxicity. NKT and γδT cells are promising synergistic therapeutic cell types that may overcome the limitations of CD3 bispecific antibodies in pancreatic tumor treatments, offering a new perspective for clinical applications in immunotherapy.
Journal
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MSLN (Mesothelin)
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zoledronic acid
19d
Alterations of bone proteins in medication-related osteonecrosis of the jaw. (PubMed, Eur J Oral Sci)
The results of the present study will help us elucidate the cellular mechanisms of MRONJ. Although culture of OLAB with zoledronate and denosumab significantly altered the protein expression patterns, future research is needed to examine the effects of bone scaffolds, biofilms, and additional cell types mimicking in vivo conditions.
Journal
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TNFA (Tumor Necrosis Factor-Alpha) • RUNX2 (RUNX Family Transcription Factor 2) • TNFSF11 (TNF Superfamily Member 11)
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Prolia (denosumab) • zoledronic acid
23d
ZiPP-LTE: Zoledronate In the Prevention of Paget's Disease: Long Term Extension (clinicaltrials.gov)
P=N/A, N=287, Enrolling by invitation, University of Edinburgh | Trial completion date: Dec 2024 --> May 2027 | Trial primary completion date: Dec 2024 --> Dec 2026
Trial completion date • Trial primary completion date
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zoledronic acid
1m
Enrollment open
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capecitabine • Prolia (denosumab) • zoledronic acid • zunsemetinib (ATI-450)
1m
Case report: Cutaneous metastasis of squamous cervical carcinoma: complete regression after molecular diagnosis. (PubMed, Front Immunol)
Only one documented case has shown that a combination of paclitaxel, carboplatin, bevacizumab, and zoledronic acid can lead to a complete metabolic response. Our study, which used two cycles of albumin-bound paclitaxel, cisplatin, and bevacizumab, followed by four cycles of the same regimen plus terprelimab for metastases with CPS scores of Programmed death-ligand 1 (PD-L1) over 10, resulted in a stable complete response for over eight months. Our contribution may assist in formulating effective treatment guidelines for the cutaneous metastasis of squamous cervical carcinoma in the future.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
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Avastin (bevacizumab) • cisplatin • carboplatin • albumin-bound paclitaxel • zoledronic acid
1m
TOPAZ: Trial of Parkinson's and Zoledronic Acid (clinicaltrials.gov)
P4, N=3500, Recruiting, California Pacific Medical Center Research Institute | Trial completion date: Oct 2026 --> Oct 2025 | Trial primary completion date: Feb 2026 --> Oct 2025
Trial completion date • Trial primary completion date
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zoledronic acid
1m
Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients. (PubMed, ESMO Open)
In this updated analysis, L plus triptorelin, with or without Z, demonstrated a statistically significant DFS improvement over T plus triptorelin for the adjuvant treatment of early BC in premenopausal patients.
Clinical • P3 data • Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HR positive
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tamoxifen • letrozole • triptorelin • zoledronic acid
2ms
DiTuSarc: Treatment With Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients With Leiomyosarcoma (clinicaltrials.gov)
P2, N=7, Completed, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Active, not recruiting --> Completed | N=10 --> 7 | Trial primary completion date: Aug 2024 --> Jan 2025
Trial completion • Enrollment change • Trial primary completion date
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zoledronic acid • Qarziba (dinutuximab beta)
2ms
A prospective, randomized controlled clinical study of the efficacy of denosumab in patients with FD/MAS who are resistant to bisphosphonate therapy (ChiCTR2400091528)
P=N/A, N=38, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
New trial
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Prolia (denosumab) • zoledronic acid
2ms
Effect of zoledronic acid on biological characteristics of cervical cancer cells. (PubMed, Afr J Reprod Health)
N-cadherin (N-cad), vimentin (Vim), p-AKT, p-GSK3β, and β-cat were markedly decreased at 50, 100, and 200 μM ZA; With the increase of ZA concentration, the biological characteristics and protein expression levels of Hela and Siha changed more markedly, showing concentration dependent characteristics (P < 0.05). It was concluded that ZA can influence the malignant biological activities of CCCs.
Journal
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CDH1 (Cadherin 1) • VIM (Vimentin) • CDH2 (Cadherin 2)
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zoledronic acid
2ms
Bisphosphonate-mineralized nano-IFNγ suppresses residual tumor growth caused by incomplete radiofrequency ablation through metabolically remodeling tumor-associated macrophages. (PubMed, Theranostics)
This study elaborates the synergistic mechanism of zoledronate and IFNγ in Nano-IFNγ/Zole to reshape suppressive TIME caused by iRFA by remodeling TAMs, and highlights the important value of metabolically induced cellular reprogramming. Since both zoledronate and IFNγ have already been approved in clinics, this integrative nano-drug delivery system establishes an effective strategy with great translational promise to overcome the poor prognosis after clinically incomplete RFA.
Journal
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IFNG (Interferon, gamma) • STAT1 (Signal Transducer And Activator Of Transcription 1) • TFEB (Transcription Factor EB 2)
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zoledronic acid
2ms
New P4 trial
|
Prolia (denosumab) • zoledronic acid
2ms
New P4 trial
|
zoledronic acid
2ms
New P1/2 trial
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Tyvyt (sintilimab) • zoledronic acid
3ms
Identification of genetic associations between acute myocardial infarction and non-small cell lung cancer. (PubMed, Front Mol Biosci)
These findings suggest that shared hub genes may serve as novel therapeutic targets for patients with both diseases. Ten candidate drugs were predicted, with zoledronic acid showing potential for targeting dual hub genes, offering a promising therapeutic approach for the comorbidity of lung cancer and myocardial infarction.
Journal
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ER (Estrogen receptor) • MIR155 (MicroRNA 155) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • COL1A1 (Collagen Type I Alpha 1 Chain) • ETS1 (ETS Proto-Oncogene 1) • CREB1 (CAMP Responsive Element Binding Protein 1) • JUNB (JunB Proto-Oncogene AP-1 Transcription Factor Subunit) • MIR124-2 (MicroRNA 124-2) • MIR93 (MicroRNA 93) • PLAU (Plasminogen Activator) • RELA (RELA Proto-Oncogene) • MIR124-3 (MicroRNA 124-3)
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zoledronic acid
3ms
Synthetic inhibition of SREBP2 and the mevalonate pathway blocks rhabdomyosarcoma tumor growth in vitro and in vivo and promotes chemosensitization. (PubMed, Mol Metab)
In human RD and RH30 lines, treatment with 0.01-1 μM doses of fatostatin (SREBP2 inhibitor), lovastatin and simvastatin (HMGCR inhibitors), and zoledronic acid (FDPS inhibitor) impaired cell growth and migration, which were conversely stimulated by 50-100 μM cholesterol (CHO) supplementation. Treatment of RMS lines with higher doses of SREBP2 and MVP inhibitors (5-50 μM) promoted oxidative cell death and chemosensitization in combination with actinomycin D. Administration of lovastatin or fatostatin to RD and RH30 cells produced a rapid attenuation of Erk1/2 and Akt1 phosphorylation, detectable after 4 hours of treatment...Taken together, these data suggest that the axis formed by Akt1, SREBP2 and MVP is critical for RMS tumor growth, migration, and oxidative stress protection mainly through the maintenance of CHO levels that ensure proper intracellular signaling. Therefore, targeting CHO levels by SREBP2 and MVP inhibition may represent a viable option to improve the combination therapy protocol in RMS.
Preclinical • Journal
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MVP (Major Vault Protein) • SQLE (Squalene Epoxidase)
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dactinomycin • zoledronic acid • simvastatin • lovastatin
3ms
Geranylgeranyl diphosphate synthase inhibition impairs osteoclast differentiation, morphology, and resorptive activity. (PubMed, JBMR Plus)
Nitrogen bisphosphonates, such as zoledronic acid, target the enzyme farnesyl diphosphate synthase (FDPS) in the isoprenoid biosynthetic pathway (IBP), and are the frontline treatment for osteolytic bone diseases...Liquid chromatography-tandem mass spectrometry studies confirmed accumulation of RAM2061 in bone from the in vivo studies as well as hydroxyapatite binding in vitro. In conclusion, these studies are the first to demonstrate the anti-osteoclastic activity of GGDPS inhibitor treatment and support future studies exploring the therapeutic benefit of this novel therapy in the setting of pathological bone remodeling.
Journal
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CDC42 (Cell Division Cycle 42)
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zoledronic acid
3ms
Zoledronic Acid Inhibits Lipopolysaccharide-Induced Osteoclastogenesis by Suppressing Macrophage NLRP3-Mediated Autophagy Pathway. (PubMed, Immun Inflamm Dis)
ZOL has a certain immunomodulatory effect that exhibits anti-inflammatory properties at lower concentrations, which can weaken LPS-induced OCs differentiation and function, and NLRP3-mediated autophagy pathway may participate in this process.
Journal
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TNFA (Tumor Necrosis Factor-Alpha) • NLRP3 (NLR Family Pyrin Domain Containing 3) • ATG7 (Autophagy Related 7) • BECN1 (Beclin 1)
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zoledronic acid
3ms
Journal
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TNFA (Tumor Necrosis Factor-Alpha) • IL1B (Interleukin 1, beta) • CRP (C-reactive protein)
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zoledronic acid
3ms
Remission of longstanding metastatic paraganglioma in a patient after use of zoledronic acid. (PubMed, BMJ Case Rep)
Stability of disease was further demonstrated by CT over several years. The patient continues on surveillance.
Journal • Metastases
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SSTR (Somatostatin Receptor)
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zoledronic acid
3ms
New P4 trial
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dexamethasone • zoledronic acid
3ms
SLFN12 Expression Significantly Effects the Response to Chemotherapy Drugs in Triple-Negative Breast Cancer. (PubMed, Cancers (Basel))
These results suggest that SLFN12 overexpression significantly affects the expressions of genes driving phenotypic changes in response to chemotherapy and influences additional SLFN family members following IFN-α2 treatment. This may contribute to improving the survival of patients with SLFN12 overexpression. Additionally, patient SLFN12 levels can be used as a factor when pursuing personalized chemotherapy treatments.
Journal
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IFNA1 (Interferon Alpha 1) • GJB3 (Gap Junction Protein Beta 3)
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carboplatin • paclitaxel • zoledronic acid
4ms
Fatty acid composition and anti-cancer activity of essential oil from Tenebrio molitor larvae in combination with zoledronic acid on prostate cancer. (PubMed, Heliyon)
In conclusion, EOTM exhibits strong anticancer properties by inducing apoptosis in prostate cancer cells and demonstrates synergistic potential when combined with zoledronic acid. These findings warrant further investigation of EOTM as a natural and effective cancer treatment option.
Journal • Combination therapy • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein)
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BCL2 expression • BAX expression
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zoledronic acid
4ms
Romosozumab As an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea (clinicaltrials.gov)
P3, N=114, Not yet recruiting, Massachusetts General Hospital | Initiation date: Oct 2024 --> Jan 2025
Trial initiation date
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zoledronic acid
4ms
Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery (clinicaltrials.gov)
P4, N=36, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed
Trial completion • Surgery • Bariatric surgery
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Prolia (denosumab) • zoledronic acid
4ms
Elotuzumab-mediated ADCC with Th1-like Vγ9Vδ2 T cells to disrupt myeloma-osteoclast interaction. (PubMed, Cancer Sci)
Human Th1-like Vγ9Vδ2 (γδ) T cells, important effectors against tumors, can be expanded and activated ex vivo by the aminobisphosphonate zoledronic acid in combination with IL-2. These results demonstrate that SLAMF7 is highly expressed in both MM cells and OCs, and that the ex vivo-expanded γδ T cells can exert ELO-mediated ADCC against SLAMF7-expressing MM cells and OCs besides their direct cytotoxic activity. Further study is warranted for the innovative utilization of γδ T cells.
Journal
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IL2 (Interleukin 2) • CSF1 (Colony stimulating factor 1) • SLAMF7 (SLAM Family Member 7)
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Empliciti (elotuzumab) • zoledronic acid
4ms
Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors (clinicaltrials.gov)
P1, N=22, Recruiting, University of Wisconsin, Madison | Suspended --> Recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
Enrollment open • Trial completion date • Trial primary completion date
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melphalan • zoledronic acid
5ms
Multifunctional ICG-SB@Lip-ZA Nanosystem Focuses on Remodeling the Inflammatory-Immunosuppressive Microenvironment After Photothermal Therapy to Potentiate Cancer Photothermal Immunotherapy. (PubMed, Adv Healthc Mater)
Indocyanine green (ICG) as a photothermal-transducer ablated tumor cells, zoledronic acid (ZA) depletes TAMs recruited by the inflammatory tumor microenvironment (mostly M2-like phenotype), SB-505124 affects CAFs proliferation in the tumor microenvironment (TME) by inhibiting the transforming growth factor-β (TGF-β) pathway, thereby removing physical barriers to T cell infiltration. In a breast cancer model, these immunomodulatory nanoliposomes markedly decrease the population of M2-like TAMs in the TME, eliminate physical barriers hindering T cell infiltration, reshape the inflammatory immune-suppressive tumor microenvironment, eventually leading to a rate of tumor eradication of 94%. This multifunctional ICG-SB@Lip-ZA nanosystem (including photothermal conversion, TAM depletion, and TGF-β pathway blockade) offers a promising strategy for mitigating the deteriorating tumor microenvironment following PTT and presents a more efficient approach for clinical photothermal-immune combination therapy.
Journal
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TGFB1 (Transforming Growth Factor Beta 1)
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zoledronic acid
5ms
An Impressive Response to Zoldronic Acid Treatment for Chronic Recurrent Multifocal Osteomyelitis: A Case Report. (PubMed, J Investig Med High Impact Case Rep)
Data on the use of zoledronic acid (ZA) in juvenile CRMO are scarce...The patient's condition stayed stable while taking naproxen (20 mg/kg/day) and methotrexate (10 mg/week) for 1.5 years until he experienced right elbow pain, swelling, no overlying skin erythema, and a restricted range of motion...Non-steroidal anti-inflammatory drugs and methotrexate were initially effective in treating our patient's condition, but a recurrence necessitated treatment modification. To the best of our knowledge, this case is the first documented instance of the use of ZA in CRMO in Iraq and Arab nations.
Journal
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CRP (C-reactive protein)
|
methotrexate • zoledronic acid
5ms
DiTuSarc: Treatment with Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients with Leiomyosarcoma (clinicaltrials.gov)
P2, N=10, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Jan 2025
Enrollment closed • Trial completion date • Metastases
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zoledronic acid • Qarziba (dinutuximab beta)
5ms
Trial suspension
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melphalan • zoledronic acid
5ms
Local Bisphosphonate Effect on Recurrence Rate in Extremity Giant Cell Tumor of Bone (clinicaltrials.gov)
P3, N=120, Recruiting, St. Louis University | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026
Trial completion date • Trial primary completion date
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zoledronic acid
5ms
New P1/2 trial
|
zoledronic acid
5ms
STAT6/LINC01637 axis regulates tumor growth via autophagy and pharmacological targeting STAT6 as a novel strategy for uveal melanoma. (PubMed, Cell Death Dis)
Finally, molecular docking indicated that STAT6 is a target of Zoledronic Acid, which can delay UM tumorigenicity by inhibiting STAT6 expression. Taken together, our results indicate that the STAT6/LINC01637 axis promotes UM progression via autophagy and may serve as a potential therapeutic target for UM.
Journal
|
STAT6 (Signal transducer and activator of transcription 6)
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zoledronic acid
5ms
The Potential of Enamel Matrix Derivative in Countering Bisphosphonate-Induced Effects in Osteoblasts. (PubMed, Life (Basel))
While the suppressive effect of zoledronate (Zol) on cell viability and migration was observed, the addition of EMD significantly mitigated this effect and enhanced cell viability and migration...This finding suggests that EMD could mitigate the effects of BPs, resulting in the recovery of cell survival, migration, and gene and protein expression. However, the behavior of the osteoblasts was not fully restored, and further studies are necessary to confirm their effects at the cellular level and to assess their clinical usefulness in vivo for the prevention and treatment of MRONJ.
Journal
|
CSF1 (Colony stimulating factor 1) • ALPL (Alkaline Phosphatase)
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zoledronic acid
6ms
Drug induced lupus associated with Trastuzumab emtansine in a patient with metastatic breast cancer. (PubMed, J Oncol Pharm Pract)
Drug-induced lupus is a clinical syndrome that shares similar features with systemic lupus erythematosus (SLE). The majority of patients present with symptoms such as arthralgia and myalgia. Hydralazine and procainamide are high-risk drugs for drug-induced lupus. Symptoms usually develop after months or years of use, but may also develop suddenly. Our patient also received TDM-1 treatment for 18 months. We present a case of TDM-1-associated drug-induced lupus in a patient with metastatic breast cancer. This is the first case of TDM-1-related drug-induced lupus reported in the literature.
Journal • Metastases
|
HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
|
docetaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine) • hydroxychloroquine • zoledronic acid
6ms
TOPaZ: Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid (clinicaltrials.gov)
P4, N=350, Active, not recruiting, University of Edinburgh | Recruiting --> Active, not recruiting | Trial completion date: Apr 2023 --> Jul 2025 | Trial primary completion date: Dec 2022 --> Feb 2025
Enrollment closed • Trial completion date • Trial primary completion date
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zoledronic acid