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Case history

image A 70-year-old man presented as an emergency admission requiring a right hemicolectomy for an obstructive caecal mass. He had a medical history of type 1 diabetes with grade 1 peripheral neuropathy, gastrointestinal reflux disease, hearing impairment, mild mitral regurgitation and benign essential tremor. The postoperative histological findings were a pT4N2 poorly differentiated KRAS-mutant adenocarcinoma with neuroendocrine differentiation. Further imaging revealed tumour recurrence at the surgical anastomosis, extensive liver metastases with no segmental sparing, and peritoneal disease. On assessment for palliative chemotherapy, the patient's Eastern Cooperative Oncology Group performance status (PS) was 2. Chemotherapy with fluorouracil (5-FU; de Gramont regimen), folinic acid (400 mg/m2/day) and irinotecan (180 mg/m2/day) every 2 weeks (FOLFIRI) was commenced 7 weeks postoperatively. Bevacizumab 5 mg/kg was added with the second cycle of chemotherapy 9 weeks after surgery.

Following 3 weeks of chemotherapy, the patient reported anorexia, more frequent yellow stool and weight loss of 19% of his original body weight. Dietary changes were advised. A week later, he reported grade 2 diarrhoea despite regular use of low-dose loperamide. A week after his third cycle of chemotherapy, the patient was admitted with faecal incontinence and grade 3 diarrhoea secondary to Clostridium difficile. He received a 5 day course of oral fidaxomicin and supportive care. His diarrhoea improved but due to persistent grade 2 diarrhoea he completed a further 5 day course of fidaxomicin. Three days after completion of the second course of antibiotics, the patient was readmitted to hospital with non-neutropenic sepsis of unknown source which responded to broad spectrum intravenous antibiotics. Restaging performed during this admission 8 weeks after commencing chemotherapy demonstrated disease progression with multi-site colonic stenosis and progressive liver, nodal and peritoneal disease.

What palliative chemotherapy regimens are recommended in older patients with metastatic colorectal cancer?

What is the risk of diarrhoea with these treatments and what are the mechanisms?

What other causes of diarrhoea need to be considered and what investigations may be required?

How is C. difficile diagnosed and managed?

How can faecal incontinence be best managed?

What palliative chemotherapy regimens are recommended in older patients with metastatic colorectal cancer?

Colorectal cancer is one of the commonest cancers diagnosed worldwide1 and approximately 60% of diagnoses are in individuals aged 70 years or older.2 Older patients are underrepresented in the clinical trial population evaluating treatment strategies in metastatic colorectal cancer,3 but pooled retrospective analyses of patients <70 years and ≥70 years have reported similar response rates, progression-free survival (PFS) and overall survival with oxaliplatin and irinotecan combined with 5-FU/folinic acid.4,5 5-FU can also be administered as an oral pro-drug, capecitabine, in combination with irinotecan (XELIRI). A meta-analysis of six phase II and III randomized controlled trials of FOLFIRI and XELIRI concluded that the efficacy of both regimens was comparable, although the median age of participants in the trials included in the meta-analysis was less than ...

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