Raltitrexed as a substitute for 5-fluorouracil in combination with pembrolizumab and platinum in a patient with metastatic esophageal squamous cell carcinoma and coronary artery disease: a case report.

Background: Chemoimmunotherapy is the standard treatment for patients with metastatic esophageal squamous cell carcinoma (ESCC), for which 5-fluorouracil (5-FU) is commonly part of the chemotherapy regimen. Given that 5-FU has a mean cardiotoxicity risk of approximately 5%, raltitrexed has often been used as an alternative in patients with a history of fluoropyrimidine-associated cardiotoxicity or significant coronary artery disease (CAD). We report the first case, to our knowledge, of the use of raltitrexed in place of 5-FU in combination with pembrolizumab and platinum-based chemotherapy for the treatment of metastatic esophageal cancer in a patient with CAD. Case Description: A 75-year-old gentleman with preexisting multivessel CAD was diagnosed with metastatic gastroesophageal junction (GEJ) squamous cell carcinoma (SCC) after presenting to medical attention with a 2-month history of worsening chest pain in addition to progressive dysphagia associated with weight loss. Following initial treatment with palliative locoregional radiotherapy to the lower mediastinum, GEJ, and upper abdomen, the decision was made to proceed with palliative systemic therapy. Considering his significant cardiac history, 5-FU was replaced with raltitrexed and combined with carboplatin and pembrolizumab. After a total of 10 months of treatment, the patient presented to hospital with recurrent chest pain and was diagnosed with a non-ST-elevation myocardial infarction (NSTEMI). Despite radiographic evidence of stability of his malignancy on systemic therapy, he was not considered to be a candidate for cardiac intervention. He was thus transitioned to a comfort-focused care approach and passed away shortly thereafter, with the cause of death being acute coronary syndrome. Conclusions: Although the patient unfortunately passed away prematurely due to preexisting CAD, there was no evidence of disease progression in the 10 months that he received treatment. In addition to an encouraging progression-free survival (PFS), the patient reported an overall improvement in quality of life while on therapy with no signals of toxicity from raltitrexed or immunotherapy. Overall, the present case demonstrates that chemotherapy in combination with immunotherapy for the treatment of advanced esophageal cancer appears to be safe and effective when raltitrexed is substituted for 5-FU, which is of particular relevance due to the many overlapping characteristics of patients with cardiac pathology and esophageal cancer.