Background: Pazopanib is an effective treatment option for renal cell carcinoma (RCC). However, the therapy is often limited by the appearance of adverse events (AEs), including nausea/vomiting, hepatic impairment, hand-foot syndrome, diarrhea, hypertension and oral mucositis. Early management of AEs is, therefore, extremely important in order to maximize treatment outcomes. Patients and Methods: This non-randomized controlled before-and-after study was carried out to evaluate the effectiveness of our comprehensive pharmaceutical interventions in 37 outpatients receiving pazopanib for RCC (experimental group). Data were compared with those obtained from 13 patients before the start of pharmaceutical intervention (control group). Results: The incidence rates of grade 2 or more nausea and anorexia were significantly lower in the experimental, than in the control group (3% versus 38% for nausea, respectively, p=0.003; 8% versus 46% for anorexia, respectively, p=0.005). Importantly, non-adherence based on patient self-assessment was not observed with intervention (0% versus 38%, p<0.001). Consequently, the median total dose of pazopanib was increased by the intervention (72,600 versus 18,200 mg, p=0.002). Moreover, the median time to treatment failure was significantly longer with intervention than before (10.2 versus 1.7 months, HR=0.23, p<0.001). These findings suggest that our interventions are highly effective for enhancing treatment outcomes.
Introduction
Pembrolizumab cause immune‐related adverse events. We herein report a case of advanced bladder cancer, who treated with pembrolizumab and exhibited intriguing clinical course.
Case presentation
A 63‐year‐old man with bladder carcinoma was treated by radical cystectomy, however, the bladder carcinoma recurred and invaded to the rectum. He was treated by combination therapy using gemcitabine and cisplatin, which were not effective for the tumor. He subsequently underwent treatment with pembrolizumab. In several 30 days, he suffered from the symptoms of myasthenia gravis. Serum levels of creatine kinase, its isozyme creatine kinase‐myocardial band, and troponin I were elevated. Electrocardiography showed a right bundle branch block. These findings suggested that he was myasthenia gravis with general myositis and presumable myocarditis. Oral prednisolone administration significantly attenuated these findings. The tumor drastically shrunk only by the single injection of pembrolizumab.
Conclusion
Early intervention with corticosteroid was effective for neuromuscular complications due to pembrolizumab.
BackgroundNivolumab has become an effective treatment option for cancer in various sites; however, this drug may cause immune-related adverse effects due to its mechanism of action. Furthermore, little has been reported on thiamine deficiency (TD) in patients receiving nivolumab treatment.MethodFrom a series of cancer patients, we reported a patient with recurrent renal cell carcinoma who developed TD after the start of nivolumab treatment.ResultsA 74-year-old man with recurrent renal cell carcinoma was referred to the psycho-oncology department as he had lost about 4 kg and displayed a loss of energy after four cycles of nivolumab treatment. Psychiatric interviews revealed a decrease in energy. Neurological examination did not reveal any impairment in consciousness, ataxia, or ocular symptoms. He did not develop appetite loss. The malabsorption or overconsumption of some nutrients is thought to occur due to the rapid loss of weight; thus, a reduction in vitamin B1, which has a short storage period in the body and is often deficient in cancer patients, was suspected. The diagnosis of TD was supported by the patient's abnormally low serum thiamine level.Significance of resultsIn patients treated with nivolumab, it is necessary to pay careful attention to TD when proceeding with the treatment. It is hoped that future research may reveal the link between nivolumab administration and TD.
Thrombohemorrhagic disorders are the main cause of morbidities and mortalities of essential thrombocythemia (ET), which are typically observed at age 50-60 years and rarely encountered in adolescence or childhood. Recently, anagrelide, a quinazinolone derivative, has been used as a therapeutic agent for ET. Although it is used to reduce platelet count, its cardiotoxicity has been reported. Here, we present an 18-year-old boy with ET who was treated with anagrelide and developed acute myocardial infarction. This was presumed to be an effect of anagrelide administration and, specifically, damage to the coronary arterial endothelial cell exacerbated by ET.
Introduction
Pazopanib, a tyrosine kinase inhibitor, and nivolumab, an immune checkpoint inhibitor, are both considered to cause hepatotoxicity with different pathophysiology. We report a case in which a patient died of severe hepatotoxicity who was presumed to have been caused by the administration of nivolumab followed by pazopanib for metastatic renal cell carcinoma.
Case presentation
A 74‐year‐old male with metastatic renal cell carcinoma was treated with nivolumab as a third‐line treatment. However, nivolumab was subsequently discontinued, as it caused severe thyroiditis. About 2 months after the final dose of nivolumab was administered, pazopanib was initiated as a fourth‐line treatment. The patient suffered from lethal hepatic failure and died 18 days after the initiation of pazopanib treatment. An autopsy revealed that CD8‐positive lymphocytes had infiltrated the thyroid gland and liver.
Conclusion
The patient was considered to have died of severe hepatic failure due to the aggravation of mild nivolumab‐induced immune‐related hepatitis by pazopanib.
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