Severe enteropathy associated with raltitrexed and oxaliplatin chemotherapy: report of two patients experiencing this rare, potentially lethal gastrointestinal adverse event.

Among the several different combination chemotherapy regimens for the treatment of patients with metastatic colorectal cancer, oxaliplatin plus raltitrexed has shown encouraging therapeutic results and a fairly good toxicity profile. Here, we report on two patients with metastatic colorectal cancer receiving this combination therapy, which leads to severe enterocolitis and neutropenia resulting in death in one patient. One patient was a 67-year-old woman suffering from an adenocarcinoma of the sigmoid colon with multiple liver metastases. The other patient was a 74-year-old woman with colon cancer, and metachronous multiple pulmonal and hepatic metastases. In both patients, palliative chemotherapy consisted of oxaliplatin 130 mg/m2 in combination with raltitrexed 3 mg/m2 on day 1 every 21 days. Both patients developed neutropenia in combination with severe enterocolitis after the fourth and the second chemotherapy cycle, respectively. Despite antibiotic treatment, diarrhea persisted in both patients for weeks. One patient died 17 days after hospital admission because of enteric sepsis with bleeding of the colonic mucosa and multiorgan failure. The other patient recovered completely and was discharged from hospital after 8 weeks. Severe enterocolitis, a hitherto infrequently recognized adverse event, which has been described in association with 5-fluorouracil/leucovorin and oxaliplatin chemotherapy, may also occur with raltitrexed and oxaliplatin. Physicians should be aware of this rare, although potentially lethal, gastrointestinal toxicity.