Background. Oncology clinical trials demonstrate the risk of cardiotoxicity but are not sufficient to reveal the true risk. In this article, we compared the incidence of cardiotoxicity of crizotinib and osimertinib from a real-world study to data reported by phase 3 clinical trials. Methods. Data from an ongoing real-world lung cancer study was used as a comparator. Patients were recruited retrospectively with the criteria of being diagnosed with non-small cell lung cancer and having received at least a course of treatment of tyrosine-kinase inhibitor and/or immune check-point inhibitor. Characteristics of the patients who developed cardiotoxicity associated with osimertinib and crizotinib in the real-world lung cancer study were analysed against the inclusion criteria of the corresponding phase 3 clinical trials. Variations of cardiotoxicity incidence among the real-world lung cancer study and clinical trials were investigated. Results. 18%, n = 37/206, of the patients developed cardiotoxicity. QTc prolongation was the most frequently observed cardiotoxicity (n = 12/37). Osimertinib and crizotinib were the most cardiotoxic agents, each responsible for seven cases of cardiotoxicity. FLAURA, AURA3, PROFILE 1007 and PROFILE 1014 were the included clinical trials for analysis. None of the patients who developed cardiotoxicity in the real-world study would have been eligible to participate in FLAURA and PROFILE 1014 study whereas n = 4/7 and n = 5/7 patients were eligible to participate in AURA3 and PROFILE 1007 trials, respectively. Conclusion. Although phase 3 clinical trials play an important role in understanding the effectiveness and give insights on side-effect profiles, real-world studies can show the real risk of cardiotoxicity more accurately and realistically.
Cardiotoxicity induced by anti-cancer treatment has become a significant threat as the number of cardiotoxic anti-cancer agents is growing. Cancer patients are at an increased risk of contracting coronavirus disease 2019 (COVID-19) because of immune suppression caused by anti-cancer drugs and/or supportive treatment. Deterioration in lung functions due to COVID-19 is responsible for many cardiac events. The presence of COVID-19 and some of its treatment modalities may increase the chance of cardiotoxicity development in cancer patients receiving potentially cardiotoxic agents. This review provides evidence-based information on the cardiotoxicity risk in cancer patients clinically diagnosed with COVID-19 who are receiving potentially cardiotoxic anti-cancer agents. Proposed strategies relating to the management of this patient cohorts are also discussed.
BackgroundAntimicrobial stewardship (AMS) is a crucial tool for rationalizing the use of antimicrobial agents and reducing the burden of antimicrobial resistance. We aimed to assess the impact of AMS interventions on antimicrobial utilization and adherence to antimicrobial guidelines.MethodsWe conducted a prospective quasi-experimental study at a major tertiary hospital in the United Arab Emirates. Using standardized World Health Organization’s methodology, point-prevalence surveys (PPS) were performed in November 2019 and January 2022. Core AMS interventions consisted of proactive bloodstream infection service, proactive and reactive infectious diseases consult service, prospective audit and feedback by clinical pharmacists, development of antimicrobial guidelines based on cumulative antibiograms, and implementation of induction programs for new clinical staff. Days of therapy (DOT) per 1000 patient days present and rate of compliance with antimicrobial guidelines were compared before and after the core interventions. Multiple logistic regression analysis was carried out to adjust for the potential confounding effects of age, gender, hospitalization within 90 days, central or peripheral line insertion, urinary catheterization, and mechanical ventilation. P-value<0.05 was considered statistically significant.ResultsPre- and post-intervention PPSs included 292 and 370 patients, respectively. Both had similar age and gender distribution. Patients receiving antimicrobials were 51% (149/292) in 2019 and 45% (166/370) in 2022 (p 0.12). Univariate analysis showed a reduced post-intervention DOT per 1000 patients present (6.1 +/- 16.2 vs 2.4 +/-5.1, p<0.01) and an improved post-intervention guideline compliance (59% vs 67%, p 0.23). Following multiple logistic regression, the reduction in post-intervention DOT remained statistically significant (co-efficient -0.17 (95% CI -8.58 to -1.94, p<0.01), and the improvement in guideline adherence became statistically significant (adjusted odds ratio 1.91 (95% CI 1.05 to 3.45, p 0.03).ConclusionCoordinated and sustained AMS interventions have a significant impact on improving antimicrobial utilisation and adherence to guidelines.
Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and challenging cancer for diagnosis and treatment. Accurate diagnosis plays a crucial role guiding appropriate treatment, typically involving high-intensity lymphoblastic leukemia regimens which typically include vincristine. However, the use of vincristine may be particularly limited in patients with pre-existing neuropathy or individuals at high risk of developing it. Here, we present a case of BPDCN that was initially diagnosed as marginal zone lymphoma (MZL) and subsequently as non-specific T-cell lymphoma, thus highlights the importance of accurate diagnosis and modified treatment. Case presentation A 49-year-old Arab man with a medical history of diabetes, peripheral neuropathy, hypertension, and depression presented with widespread, painless multiple skin lesions. After undergoing a biopsy at another institution, the patient was initially diagnosed with MZL, and received two cycles of bendamustine and rituximab. However, the disease relapsed and was later diagnosed with non-specific T-cell lymphoma, which proved refractory to a single cycle of CHOP chemotherapy. The patient was subsequently referred to our centre, where a comprehensive evaluation revealed BPDCN with a unique finding on bone marrow exam: signet ring plasmacytoid dendritic cells. Due to the patient's pre-existing neuropathy and previous treatment, we administered the Hyper-CVAD regimen with a 50% reduction in vincristine dosage, which resulted in an excellent response. During the second part of cycle one, when new skin lesions started appearing, venetoclax was added to the treatment regimen. Subsequently, we discontinued vincristine due to worsening neuropathic pain and neuropathy-related weakness. Venetoclax was continued in cycle two and led to a complete response. The patient achieved a disease-free state for the first time in disease course, maintaining it for a period of over six weeks before experiencing a relapse. Conclusions Accurate diagnosis is crucial for guiding appropriate treatment. Our case highlights the challenges associated with diagnosis and treatment, as well as the potential of venetoclax as an alternative to vincristine, particularly in patients with pre-existing neuropathy or those at a high risk of developing it. Further research is needed to evaluate the effectiveness of BCL2 inhibitors as a replacement for essential drugs and its potential as a bridging therapy until patients can undergo a stem cell transplant.
Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and challenging cancer for diagnosis and treatment. Accurate diagnosis plays a crucial role guiding appropriate treatment, typically involving high-intensity lymphoblastic leukemia regimens which typically include vincristine. However, the use of vincristine may be particularly limited in patients with pre-existing neuropathy or individuals at high risk of developing it. Here, we present a case of BPDCN that was initially diagnosed as Marginal Zone Lymphoma (MZL) and subsequently as non-specific T-cell lymphoma, thus highlights the importance of accurate diagnosis and modified treatment. Case presentation: A 49-year-old Arab man with a medical history of diabetes, peripheral neuropathy, hypertension, and depression presented with widespread, painless multiple skin lesions. After undergoing a biopsy at another institution, the patient was initially diagnosed with MZL, and received two cycles of bendamustine and rituximab. However, the disease relapsed and was later diagnosed with non-specific T-cell lymphoma, which proved refractory to a single cycle of CHOP chemotherapy. The patient was subsequently referred to our centre, where a comprehensive evaluation revealed BPDCN with a unique finding on bone marrow exam: signet ring plasmacytoid dendritic cells. Due to the patient's pre-existing neuropathy and previous treatment, we administered the Hyper-CVAD regimen with a 50% reduction in vincristine dosage, which resulted in an excellent response. During the second part of cycle one, when new skin lesions started appearing, venetoclax was added to the treatment regimen. Subsequently, vincristine was completely removed, and venetoclax was continued in cycle two, leading to a complete response. The patient achieved a disease-free state for the first time in disease course, maintaining it for a period of over six weeks before experiencing a relapse. Conclusion: Accurate diagnosis is crucial for guiding appropriate treatment. Our case highlights the challenges associated with diagnosis and treatment, as well as the potential of venetoclax as an alternative to vincristine, particularly in patients with pre-existing neuropathy or those at a high risk of developing it. Further research is needed to evaluate the effectiveness of BCL2 inhibitors as a replacement for essential drugs and its potential as a bridging therapy until patients can undergo a stem cell transplant.Top of Form
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