Raltitrexed as a substitute for capecitabine in metastatic gastric cancer: a case report and literature review

BACKGROUND: 5-Fluorouracil and its oral prodrug, capecitabine, are frequently used in the treatment of gastrointestinal cancers—including gastric cancer—but carry a cardiotoxicity risk. Raltitrexed (brand name Tomudex), a direct inhibitor of thymidylate synthase, has been successfully used as an alternative to fluoropyrimidines in patients with 5-fluorouracil-induced cardiac events. We report the first case, to our knowledge, of raltitrexed used with trastuzumab and platinum-based chemotherapy as a substitute for fluoropyrimidines following cardiotoxicity in a 78-year-old male patient with metastatic gastric cancer. CASE DESCRIPTION: The patient experienced a myocardial infarction 3 days after beginning treatment with capecitabine, carboplatin, and trastuzumab for metastatic HER2(+) gastric adenocarcinoma. Capecitabine was replaced with raltitrexed, and the patient ultimately received seven cycles of chemotherapy, five of which included raltitrexed. There were no cardiotoxic events attributable to raltitrexed, although the patient did experience hypotensive episodes, premature ventricular contractions, myelosuppression, and anemia. Progression-free survival was 4.5 months, within the expected range achieved with the ToGA regimen (trastuzumab, cisplatin, 5-fluorouracil chemotherapy). At time of writing, the patient has been alive for 48 weeks since diagnosis. CONCLUSIONS: In summary, raltitrexed appears to be a safe alternative to fluoropyrimidines when combined with trastuzumab and platinum, although more data is needed to determine its relative effectiveness.