Signals mining and analysis of adverse drug events of pazopanib based on FAERS database / 中国药房

OBJECTIVE To mine and analyze adverse drug event （ADE） signals after the marketing of pazopanib and provide references for clinically safe medication. METHODS OpenVigil 2.1 data platform was used to mine ADE signals from the US FDA adverse event reporting system （FAERS） database. ADE reports of pazopanib from October 2009 to June 2022 were collected， and ADE signals were analyzed using proportional reporting ratio （PRR） method and reporting odds ratio （ROR） method in the proportional imbalance method. RESULTS A total of 16 655 ADE reports were identified with pazopanib as the primary suspect drug. Through ROR and PRR analysis， 220 ADE signals involving 19 system organ classes were identified. The top 10 ADE signals by frequency were recorded in the drug instruction. Additionally， 88 new ADE signals were discovered， mainly related to the gastrointestinal system， various investigations， and the renal and urinary system. Decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula were both new ADE signals and the top 10 ADE signals by strength. CONCLUSIONS The occurrence of common ADEs （diarrhea， hair color changes， hypertension， etc.） during the use of pazopanib after marketing is generally consistent with its drug instruction； the number of reported cases for new suspected risk signals （decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula， etc.） is limited， and continuous monitoring is required.

LDHA inhibitor combined with targeted drugs synergistically inhibit the proliferation of fumarate hydratase-deficient renal cell carcinoma cells / 现代泌尿外科杂志

【Objective】 To explore the therapeutic effects of lactate dehydrogenase A (LDHA) inhibitor and targeted drugs on fumarate-hydratase-deficient renal cell carcinoma (FH-d RCC). 【Methods】 RNA-sequencing was used to detect the mRNA expression in FH-d RCC tissues, which was further validated with real-time fluorescence quantitative PCR and immunohistochemistry. Human-derived FH-d RCC cell line UOK262 and murine-derived FH-d RCC cell line FH1-/-CL19 (CL19) were treated with LDHA inhibitor [(R)-GNE-140] and listed kidney cancer targeted drugs (Axitinib, Cabozantinib, Sunitinib, Sorafenib, Pazopanib, Everolimus) respectively, and then treated with LHDA inhibitor in combination with the targeted drugs to observe the alteration of cell proliferation. The combination index (CI) of different dose groups of the combination drugs were analyzed with CompuSyn software to determine the optimal combination regimen. 【Results】 LDHA inhibitor and targeted drugs, including Cabozantinib, Sorafenib and Sunitinib, had a significant inhibitory effect on the proliferation of FH-d RCC cells, and the combination of Cabozantinib and Sorafenib or Pazopanib had a significant anti-tumor effect. 【Conclusion】 LDHA inhibitor combined with targeted drugs can significantly inhibit the growth of FH-d RCC cells, indicating that LDHA may be a potential therapeutic target of FH-d RCC.

Medication-Related Osteonecrosis of the Jaw Associated with Pazopanib Monotherapy

ABSTRACT: Pazopanib, an antiangiogenic agent, has shown promising results in controlling tumor growth and metastasis in patients with renal cell carcinoma. The use of pazopanib in the management of malignancies has increased over recent years, with more patients at risk of developing medication-related osteonecrosis of the jaw (MRONJ). This paper presents the first case report of MRONJ associated with pazopanib monotherapy. A 59-year-old man was referred to the dental clinic with complaints of dysphagia and dysgeusia. The patient was prescribed pazopanib (400 mg) daily following surgical treatment and chemotherapy for metastatic renal cell carcinoma. He had undergone extraction of the maxillary left second premolar nine weeks previously. Intraoral examination revealed exposed necrotic bone, which was treated effectively with leukocyte and platelet-rich fibrin (LPRF). The patient was followed up for 150 days after dental treatment with no signs of relapse.

RESUMEN: Pazopanib, un agente antiangiogénico, ha mostrado resultados prometedores en el control del crecimiento tumoral y las metástasis en pacientes con carcinoma de células renales. El uso de pazopanib en el tratamiento de las neoplasias malignas ha aumentado en los últimos años, con más pacientes en riesgo de desarrollar osteonecrosis de la mandíbula relacionada con la medicación (MRONJ). Este artículo presenta el primer reporte de caso de MRONJ asociado con la monoterapia con pazopanib. Un hombre de 59 años fue remitido a la clínica dental con quejas de disfagia y disgeusia. Al paciente se le prescribió pazopanib (400 mg) al día tras tratamiento quirúrgico y quimioterapia por carcinoma metastásico de células renales. Había sido sometido a extracción del segundo premolar superior izquierdo nueve semanas antes. El examen intraoral reveló hueso necrótico expuesto, que fue tratado eficazmente con leucocitos y fibrina rica en plaquetas (LPRF). El paciente fue seguido durante 150 días después del tratamiento dental sin signos de recidiva.

A Long-Term Survival Case after Successful Five-Fold Surgical Intervention for Recurrent Undifferentiated Pleomorphic Sarcoma in the Left Atrium / 日本心臓血管外科学会雑誌

Primary cardiac undifferentiated pleomorphic sarcoma is rare and is associated with very poor survival. We report a case of a 45-year-old female who presented with dyspnea on effort, in whom an echocardiographic exam showed a large mass in the left atrium and the tumor resection was performed. The pathological diagnosis of the resected tumor was undifferentiated pleomorphic sarcoma which subsequently recurred. The patient needed four re-surgeries, and chemotherapy with Pazopanib was performed. A long-term survival of 5 years after the initial surgery was achieved.

Paraganglioma metastásico pulmonar con respuesta a pazopanib. reporte de un caso y revisión de la literatura / Pulmonary metastatic paraganglioma with response to pazopanib. Case report and literature review

RESUMEN: El paraganglioma es un tumor neuroendocrino dependiente del sistema nervioso parasimpático que se encuentra generalmente en localización adrenal y extra-adrenal. En general son de mal pronóstico, siendo el tratamiento primario cirugía, con pobre respuesta a quimioterapia. Presentamos el caso clínico de una paciente con paraganglioma metastásico pulmonar de primario desconocido con respuesta favorable a pazopanib.

ABSTRACT: The paraganglioma is a dependent of the parasympathetic nervous system is generally in adrenal and extra-adrenal neuroendocrine tumor location. They are generally poor prognosis, surgery remains the primary treatment, with poor response to chemotherapy. We report the case of a patient with pulmonary metastatic paraganglioma of unknown primary with a favorable response to pazopanib

Literature Study on Pharmacoeconomics Evaluation of First-line Therapy Drugs for Metastatic Renal Carcinoma as Sunitinib ，Sorafenib and Pezopanib / 中国药房

OBJECTIVE：To evaluate the economics of first-line therapy drug for metastatic renal cell carcinoma （mRCC）as sunitinib，sorafenib and pazopanib ，and to provide reference for the adjustment of medical insurance list and clinical medication decision. METHODS ：Using“metastatic renal cell carcinoma ”“mRCC”“sunitinib”“sorafenib”“pazopanib”“cost-effectiveness” “cost-utility”“cost-benefit”“economic analysis ”as the Chinese and English retrieval words ，relevant literatures published during Jan. 1st，2006 to Jul. 15th，2019 were retrieved from PubMed ，Web of Science ，the Cochrane Library ，CNKI，Wanfang database ， VIP. The literatures were screened according to inclusion and exclusion criteria . The quality of the included literatures was evaluated with CHEERS scale. The effectiveness and economy of sunitinib ，sorafenib and pezoparib in the treatment of mRCC were compared qualitatively after the relevant data were extracted. RESULTS ：A total of 10 literatures were included ，and the total coincidence rates of 7 literatures over 75.00％. Among the 4 literature studies of sulatinib vs. sorafenib ，3 literature studies pointed out that sulatinib was the absolute advantage scheme ，and 1 literature study pointed out that sorafenib was more economical ； among the 6 literature studies of sunitinib vs. pezoparib ，4 literature studies indicated that pezoparib was the absolute advantage scheme，and 2 literature studies indicated that sunitinib was more economical. CONCLUSIONS ：In most cases ，the efficacy and economy of pezoparib in the treatment of mRCC is better than sunitinib and sorafenib ，but real world data shows that sunitinib is more economical.

Bilateral Rhegmatogenous Retinal Detachments after Systemic Pazopanib Treatment

PURPOSE: A case of bilateral rhegmatogenous retinal detachment is reported after pazopanib treatment of a patient with breast angiosarcoma. CASE SUMMARY: A 53-year-old female presented with bleeding in a right breast mass prior to an emergency room visit. She was diagnosed with metastatic breast angiosarcoma after a breast mass biopsy. She was treated with paclitaxel and radiation therapy. Systemic pazopanib treatment was added to treat lung metastasis. After 3 weeks, she felt sudden floaters in her right eye. In her fundus examination, there was vitreous hemorrhage, but no retinal detachment was noted. Five weeks later, she visited the clinic for a bilateral temporal visual field defect. A fundus examination showed bilateral retinal detachments with superonasal retinal tears. Both the patient and her family did not want surgery for her systemic condition because of her terminal cancer. CONCLUSIONS: Retinal detachment has been reported as a rare complication after systemic pazopanib treatment, but there has been no previous report in the Republic of Korea, therefore this is the first case of bilateral retinal detachments after systemic pazopanib treatment.

Tumor renal benigno versus carcinoma renal: reporte de caso y revisión de la literatura / Benign Kidney Tumor versus Renal Carcinoma: Case Report and Literature Review

Introducción El cáncer renal representa 2,4% de los casos diagnosticados de cáncer en la población general, es más común en hombres que en mujeres, y se presenta con más frecuencia entre la 6ta y la 8ta décadas de vida. Se estima que el 16% de los pacientes se diagnostican como enfermedad metastásica. Objetivo Se presenta el caso de un paciente cuyo diagnóstico de carcinoma renal se confundió inicialmente con un tumor benigno. Métodos A un hombre de 56 años de edad se le realizó hace 3 años ese diagnóstico en un estadio avanzado de la enfermedad, a pesar del hallazgo incidental de una masa, que se consideró benigna durante 5 años. Resultados Al momento del diagnóstico de carcinoma de células claras, el tumor era Estadio IV, con metástasis a pulmón. Recibió primera línea de tratamiento con sunitinib, pero fue suspendido por toxicidad; segunda línea con pazopanib durante 1 año, después presentó progresión de la enfermedad, por lo cual se cambió a tratamiento con axitinib con respuesta parcial, sin embargo, se suspendió por toxicidad cardiaca, entre otras. Al momento el paciente ha recibido 5 ciclos de bevacizumab con adecuada tolerancia. Conclusiones Es necesario resaltar la indicación de diagnóstico adecuado y manejo quirúrgico en masas renales sospechosas.

Introduction Kidney cancer represents 2.4% of diagnosed cases of cancer in the general population; it is more common in men than in women, and occurs more frequently between the 6th and 8th decades of life. It is estimated that 16% of patients are diagnosed as metastatic disease. Objective To report the case of a male patient whose diagnosis of renal carcinoma was initially misdiagnosed as a benign tumor. Methods We present a 56-year-old male diagnosed three years back with malignancy at an advanced stage of the disease, despite the incidental finding of a tumor that for 5 years was considered benign. Results At the time of diagnosis of clear cell carcinoma, the tumor was Stage IV, with lung metastasis. He received first line treatment with sunitinib, which was discontinued due to toxicity. Subsequently, a second line with pazotinib for 1 year, then presented progression of the disease, so treatment was changed to axitinib with partial response., It was discontinued, however, due to cardiac toxicity, among others. At the time of writing, the patient has received 5 cycles of bevacizumab with adequate tolerance. Conclusions It is necessary to highlight the need for adequate diagnosis and surgical management in suspicious renal masses.

Efficacy of First-Line Targeted Therapy in Real-World Korean Patients with Metastatic Renal Cell Carcinoma: Focus on Sunitinib and Pazopanib

BACKGROUND: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. METHODS: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. RESULTS: The median follow-up was 16.4 months (interquartile range, 8.3–31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. CONCLUSION: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.

Pazopanib for the Treatment of Non-clear Cell Renal Cell Carcinoma: A Single-Arm, Open-Label, Multicenter, Phase II Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC. MATERIALS AND METHODS: Patients with locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4 weeks and tumor response was evaluated every two cycles. The primary objective was overall response rate (ORR). RESULTS: A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay. CONCLUSION: In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.

Positive response of a primary leiomyosarcoma of the breast following salvage hyperthermia and pazopanib

No abstract available.

Advances in molecular targeted therapy for soft tissue sarcomas / 中国肿瘤临床

Sarcomas are tumors of mesenchymal origin that account for approximately 1%of human cancers. There are at least 60 dif-ferent subtypes of soft tissue sarcoma (STS). However, most tumor types are highly malignant tumors that lack an optimal therapeutic agent. Although gastrointestinal stromal tumor (GIST) responds well to imatinib, other types of STSs remain challenging because of their heterogeneous genetic and clinical features and poor prognosis. In recent years, the field of molecular targeted therapy has pro-gressed rapidly. Patients with advanced disease can receive individualized treatment to improve their quality of life. This review focus-es on the targeted therapies that have been evaluated for advanced non-GIST STS. Other promising novel therapeutic agents that are currently in the early phases of investigation are also presented.

Study on pharmacokinetics of pazopanib in rats / 药学实践杂志

Objective To develop a UPLC-MS method for the determination of pazopanib in rat plasma, and study the pharmacokinetics of pazopanib in rats.Methods The effective UPLC MS/MS separation of the examined compounds was applied on an Acquity BEH C18 column with a gradient mobile phase system.AB Sciex QTRAP 5500 triple quadruple mass spectrometer equipped with an electrospray ionization (ESI) interface was used for mass spectrometric detection.The MRM transitions of m/z 438.3→357.2 and m/z 285.2→193.1 were used to quantify for pazopanib and ISTD, respectively;6 rats were given 80 mg/kg pazopanib intragastric administration.Blood samples were collected from the tail vein at different point after administration.The concentration of pazopanib in plasma was detected by the UPLC-MS methods.The pharmacokinetics parameters were analyzed by DAS program.Results Pazopanib and ISTD were eluted at 1.10 and 1.37 min respectively.Excellent liner relationship was obtained from the range of 0.25 μg/ml to 40.00 μg/ml (r=0.999 2).The intra-day RSD were 6.17%, 2.73% and 2.54% and inter-day RSD were 7.56%, 5.98% and 2.84% respectively at three concentrations (0.50, 10.00, 30.00 μg/ml), the recoveries were (78.4±4.8)%, (85.9±3.5)% and (81.1±4.2)% respectively, the Matrix effect were (106.7±5.3) %, (101.3±6.7) % and (97.6±4.4) % respectively at three concentrations (0.50, 10.00, 30.00 μg/ml);6 rats were given 80 mg/kg pazopanib intra-gastric administration.The main pharmacokinetics parameters of pazopanib were as following: cmax (20.22±1.95) μg/ml,tmax (1.75±0.76) h,t1/2 (7.35±2.31) h,AUC0-t (213.16±39.92) μg·h/L,AUC0-∞ (215.79±39.84) μg·h/L,Vd (4.10±1.78) L/kg,CL (0.38±0.07) L/h.Conclusion The method was simple, rapid, accurately,which could be used to determine the pazopanib concentration in rat plasma and study on its pharmacokinetics.Pazopanib was fitted to the first-order elimination kinetics in rats.

Trial of Pazopanib in Proximal-type Epithelioid Sarcoma / 대한피부과학회지

No abstract available.

Progress of pazopanib in clinical applications and adverse drug reaction / 药学实践杂志

Pazopanib is a multi-targeted tyrosine kinase inhibitor ,and is mainly used to treat renal cell carcinoma ,ovari-an cancer ,breast cancer ,and lung cancer .The researchers also found that pazopanib may cause diarrhea ,hypertension ,hair loss ,nausea ,and anorexia .This paper reviewed pazopanib clinical application and adverse reactions ,and provided a basis for this medication .

Heart Failure Secondary to Pazopanib for Treatment of Metastatic Renal Cell Carcinoma / 대한내과학회지

A 78-year-old man was diagnosed with renal cell carcinoma, and left nephrectomy was performed. He started pazopanib. One month later, he visited our hospital because of general weakness and dyspnea. His oxygen saturation was low. A chest X-ray showed pulmonary edema and bilateral pleural effusion. An echocardiogram showed a larger left ventricle and lower ejection fraction than observed at the previous examination. The patient discontinued pazopanib and started diuretics and digoxin. His symptoms improved and a follow-up X-ray showed improvement in the pulmonary edema with bilateral pleural effusion.

Durable Response to Pazopanib in a Patient with Metastatic Alveolar Soft Part Sarcoma / 이화의대지

Alveolar soft part sarcoma (ASPS) is a rare form of soft tissue sarcoma, and frequently, metastases are found at diagnosis. In patients with metastatic or unresected ASPS, systemic treatment is extremely limited, because conventional chemotherapeutic agents have not been effective in most cases. A novel agent inhibiting angiogenesis, pazopanib, has been proven to be effective for metastatic soft tissue sarcoma in a second-line setting. However, the efficacy of pazopanib in ASPS has not yet been reported. A 22-year-old man presented with right calf ASPS and multiple lung metastases. Pazopanib as a second-line treatment showed significant tumor response. To the best of our knowledge, this is the first report of the effectiveness of pazopanib in ASPS.

Pazopanib-induced Hair Depigmentation, Ulcerative Patch in a Patient with Metastatic Renal Cell Carcinoma / 대한피부과학회지

No abstract available.

Pazopanib for Non-small Cell Lung Cancer: The First Case Report in Korea / Journal of the Korean Cancer Association, 대한암학회지

Pazopanib is a potent multitargeted tyrosine kinase inhibitor that has been shown to have good efficacy in patients with renal cell carcinoma. A previous phase II trial demonstrated that short-term pazopanib administration was generally well tolerated and showed antitumor activity in patients with early-stage non-small cell lung cancer. Herein, we report on the case of a 66-year-old man with simultaneous metastatic squamous cell carcinoma of the lung and renal cell carcinoma who was treated with pazopanib. The patient showed an unexpected partial response and experienced a 10-month progression-free survival without significant toxicity. To the best of the authors' knowledge, this is the first report of pazopanib treatment in a non-small cell lung cancer patient in Korea. The results in this patient suggest that pazopanib may be a valid treatment option for advanced non-small cell lung cancer.

Treatment of a Patient with Kaposi's Sarcoma Arising during Hemodialysis with the Multikinase Inhibitor Pazopanib / 대한내과학회지

Kaposi's sarcoma (KS) is an unusual multifocal neoplastic angioproliferative disorder. We herein report a case of classic KS that occurred in a patient receiving hemodialysis for 7 years. The patient had a history of chronic renal failure due to glomerulonephritis for 20 years. Multiple reddened violaceous patches, plaques, and nodules were found on the right knee. Biopsy revealed positivity for human herpesvirus 8 (KS-associated herpesvirus) consistent with KS. Pazopanib, a multitarget tyrosine kinase inhibitor, is an effective agent for treatment of advanced soft tissue sarcoma. The patient received pazopanib for 6 months investigate its effects on KS. The skin lesions and painful symptoms showed improvement. Further studies are required to determine the mechanism underlying the anticancer action of pazopanib and the pathogenesis of KS.