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Introduction Fluoropyrimidines (FP) are cornerstone drugs in the treatment of gastrointestinal (GI) malignancies. Cardiotoxicity secondary to an FP chemotherapy is a serious complication. There are no standardized guidelines on the treatment of FP induced cardiotoxicity which may result in interruption and even discontinuation of life saving treatment. We present our experience in FP rechallenge using a novel outpatient regimen based on our “up-front” triple agent antianginal protocol. Methods We report the retrospective study of the patients with suspected FP induced cardiotoxicity. Patients meeting the criteria were selected by C3OD (curated cancer clinical outcomes database) at Kansas University Medical Center (KUMC). We identified all patients with gastrointestinal malignancies who had suspected FP induced cardiotoxicity from January 2015 to March 2022. We then included the patients who were rechallenged with planned fluoropyrimidine regimen utilizing the three drug KU-protocol. We utilized a novel regimen by repurposing the already FDA-approved anti-anginal drugs in a manner that minimizes the risk of hypotension and bradycardia. Results In this retrospective study, 10 patients with suspected fluoropyrimidine induced cardiotoxicity were included from January-2015 to March-2022 at KUMC. Out of 10 patients who were rechallenged utilizing KU-protocol, eight patients (80%) were able to complete the previously planned fluoropyrimidine regimen. None of the patients required ER visits or hospital admission due to cardiac symptoms during the rechallenge utilizing the KU-protocol. Conclusions Utilizing our novel outpatient regimen, we have successfully and safely allowed re-challenge of FP chemotherapy with good tolerability and completion of the intended course of chemotherapy without recurrent morbidity.

Background Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis. First-line multikinase inhibitors like sorafenib and lenvatinib are poorly tolerated and have low response rates. Several clinical trials have shown tolerability and efficacy of immunotherapy in this setting. The objective of this retrospective study was to determine the outcomes of front-line nivolumab in a frail real-world population. Observations In this retrospective study conducted between January 2016 and December 2019, 14 men (median age, 63.5 years; range, 58-72 years) with HCC received nivolumab as front-line systemic therapy. Only 2 patients had a response to immunotherapy (14.3%), of which 1 patient had a complete response (7.1%). The median progression-free survival was 4 months and median overall survival was 8 months. Incidence of grade 3 or higher toxicity was 35%. Conclusions In our small, real-world cohort of patients receiving immunotherapy as front-line systemic treatment for HCC, outcomes were poor with front-line immunotherapy.

Background Immunotherapy has shown survival benefit as both frontline and subsequent therapy in multiple cancers. However, its efficacy in patients with poor performance status is unknown since they are excluded from the clinical trials. We conducted a retrospective study to investigate the effect of poor performance status (PS) on survival in patients with non-small cell lung cancer (NSCLC) who received immunotherapy as a subsequent line of treatment. Methods We reviewed the medical records of 341 patients with NSCLC receiving immunotherapy as between July 2013 and June 2018. Progression-free survival and overall survival was calculated using Kaplan-Meier curve. Results The average age of patients was 66 years (range: 39–90 years), with a male predominance (57%). Majority of the patients were Caucasian (87%), followed by African-American (12%), and Asian (1%). Most of the patients were former smoker (72%), followed by current smoker (19%) and never smoker (7%). Adenocarcinoma and squamous cell carcinoma was diagnosed in 206 (60%) patients and 112 (33%) patients, respectively. The ECOG-PS was 0, 1, 2 and 3 in 46 (13%), 175 (51%), 86 (25%) and 34 (10%), respectively. Four different immunotherapies were used, namely atezolizumab in 10 (3%), durvalumab in 34 (10%), nivolumab in 152 (44%) and pembrolizumab in 144 (42%) patients. Average number of cycles of atezolizumab received by the patient was 6 (range 2–22 cycles), durvalumab 15 (range 1–29 cycles), nivolumab 11 (range 1–112 cycles), and pembrolizumab 12 (range 1–52 cycles). Patients were grouped in good performance status (ECOG 0–1) and poor performance status (ECOG ≥2). The median progression free survival (PFS) was 7 months (95% CI 6.3–8.2) in patients with good PS and 3 months (95% CI 1.8–4.6) in patients with poor performance status (p Conclusions Our data suggests that while the patients with poor PS tolerated the immunotherapy. However, poor PS was associated with significantly lower PFS and OS. Further studies are required to evaluate the effect of PS on survival in frontline immunotherapy. Acknowledgements We thank Dr. Saqib Abbasi for helpful discussions. Trial Registration N/A Ethics Approval The study was approved by the Institution Review Board at KUMC, #CR00009003. References N/A

e15613 Background: Fluoropyrimidines, such as 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapies for solid tumors, and essential for curative intent treatment of colorectal cancer. But sometimes, their use may be limited by cardiac toxicity limiting the possibility of cure in some patients. Cardiotoxicity could be asymptomatic (EKG changes) or manifested as chest pain, arrhythmias, acute coronary syndrome or death. Rechallenging may be daunting and it may result in interruption or even discontinuation of planned chemo. Traditionally, nitrates and/or IV/oral calcium channel blockers (CCB) have been used for management of fluoropyrimidine-induced cardiotoxicity but without much benefit. Ranolazine, an oral antianginal drug approved for chronic angina, diminishes myocardial ischemia by reducing calcium overload caused by inhibition of late sodium current and it does not affect heart rate or blood pressure. Our objective was to evaluate the efficacy of our novel approach using ranolazine with other traditional drugs. Methods: 8 patients (median age 49.5 yrs) with fluoropyrimidine induced cardiotoxicity were retrospectively analyzed. They were rechallenged with the planned fluoropyrimidine regimen with our 3 drug cardioprotective regimen (KU protocol). This included oral Ranolazine 1000mg BID and Amlodipine 2.5 mg daily to start the day before starting 5FU infusion/oral capecitabine and to continue it until the day after completion of infusion/treatment, and Nitroglycerin paste 1 inch every 6 hours starting before infusion and continue until it was completed. These meds were discontinued upon completion of chemo. Results: 8 patients were rechallenged with fluoropyrimidine utilizing KU protocol, 6 patients (75%) were able to complete previously planned fluoropyrimidine regimen. One pt (*) discontinued capecitabine due to recurrent chest pain and treatment was switched to 5FU based regimen with KU protocol, which pt was able to complete without chest pain. Another pt (**), 5FU was stopped due to severe diarrhea, not due to cardiotoxicity. All pts tolerated KU protocol well. Conclusions: In our small, single center experience, we were able to safely and effectively rechallenge pts with fluoropyrimidines and complete curative intent treatment with our KU protocol. This protocol uses FDA approved oral and transcutaneous drugs without requiring a healthcare personnel to administer an IV CCB that can cause precipitous bradycardia and/or hypotension. Our results need validation in a larger cohort. [Table: see text]

Anti-N-methyl-D-aspartate-Receptor (NMDAR) encephalitis is an autoimmune disorder with a multifaceted presentation that involves memory deficits, psychiatric symptoms, and autonomic instability. This case report describes the classic presentation of Anti-NMDAR encephalitis and highlights its association with ovarian teratomas. We present a 26 -year-old female who came in with new onset seizures and altered mentation who subsequently developed automatism. Electroencephalograms (EEG) showed left frontal spikes and right temporal delta activity. Magnetic resonance imaging (MRI) revealed right temporal hyper-intensity. The diagnosis was established with positive anti-NMDAR antibodies in the cerebrospinal fluid (CSF). The patient was initially treated with steroids and valproic acid, however, her condition progressively worsened. A five-day course of intravenous immunoglobulins (IVIG) was started followed by rituximab. The clinical course was complicated with the patient developing neutropenic fever and cerebrospinal fluid cultures (CSF) growing methicillin-sensitive Staphylococcus aureus (MSSA). She underwent pelvic imaging which showed a right ovarian teratoma. Evidence suggests that removal of ovarian tumor leads to better clinical and mortality outcomes in patients with Anti-NMDAR encephalitis. It is important for the internist to consider paraneoplastic syndromes in patients with Anti-NMDAR encephalitis.