Initiating Treatment with Low Fluorouracil Dose and Titrating According to Blood Levels in Patients Treated with a 46-Hour Continuous Infusion.

INTRODUCTION: Fluorouracil (5-FU) pharmacokinetics are variable, leading to a risk of toxicity in some patients and underdosing in others. Therapeutic drug monitoring of 5-FU was shown to reduce toxicity and increase efficacy. This study assessed the clinical utility of starting treatment with 70-80% of BSA calculated dose and titrating according to 5-FU blood levels and toxicity. METHODS: A retrospective analysis of a prospectively collected database of 126 patients treated with regimens containing 5-FU bolus and continuous infusion for 46 h for whom the 5-FU blood level was collected at least once. Response,and date of progression, and death were collected for patients with colon and pancreatic cancer. RESULTS: In multivariate analysis, 5-FU blood levels were correlated with 5-FU dose and with age, albeit a small effect size (coefficient = 0.007). Of patients with colon cancer treated with an initial lower 5-FU dose, 18% had a therapeutic 5-FU blood level. The median survival was similar in patients with metastatic colon cancer treated with lower doses and those treated with a full dose. Of patients with pancreatic cancer treated with lower doses, 40% had therapeutic blood levels. The median survival was 13 months in patients with metastatic pancreatic cancer treated with lower 5-FU doses. CONCLUSION: Starting treatment with low 5-FU dose was associated with patient survival comparable to other published data, and a sizeable percentage of patients had therapeutic blood levels. This approach can be considered, especially in elderly and frail patients.

Pro-BNP in the differential diagnosis of dyspnea in patients treated with immune-checkpoint inhibitors: Case Report.

INTRODUCTION: Immune checkpoint inhibitors (ICI) induced cardiac toxicity can present with non-specific symptoms and signs. Early recognition and treatment are important; however, diagnosis can be challenging. CASE REPORT: We describe a 67-year-old woman with a history of ICI induced pneumonitis who presented with dyspnea, hypoxemia and pulmonary infiltrates while treated with pembrolizumab for lung cancer, initially diagnoses with relapssed pneumonitis. When her condition did not improve with steroids, NT-pro-BNP level was tested and was markedly high, prompting additional tests for heart failure. MANAGEMENT AND OUTCOME: The patient was diagnosed with ICI induced left ventricular dysfunction and treated with steroids, beta blockers, diuretics, and ACE inhibitors. Her symptoms and imaging studies markedly improved. DISCUSSION: Here, we review the literature on ICI induced cardiac toxicity and the role of NT-pro -BNP in triage of patients presenting with dyspnea in the emergency setting. We suggest that measurement of NT-pro -BNP be utilized in patients receiving ICI's and presenting with respiratory abnormalities, to rapidly assess for possible cardiac toxicity.