Using a combination of thalidomide and irinotecan for treating metastatic colorectal cancer virtually eliminates the adverse gastrointestinal effects of irinotecan, US researchers have found. The use of both drugs allowed patients to complete chemotherapy, while avoiding deterioration of nutritional status and improving quality of life.
Thalidomide has antiangiogenic and immunomodulatory properties and is being investigated as an antineoplastic, say Dr Rangaswamy Govindarajan (University of Arkansas for Medical Sciences, Little Rock) and colleagues. They conducted a pilot study to investigate the safety and efficacy of combining irinotecan with thalidomide for metastatic colorectal cancer. An interim analysis found that thalidomide "almost eliminated the dose-limiting gastrointestinal toxic effects of irinotecan."
In the study, patients with metastatic colorectal cancer received 400mg/day of thalidomide and 325-350mg/m2 irinotecan every 21 days. The analysis of nine patients was completed after they had had between two and eight cycles of irinotecan. The results showed a "striking" absence of gastrointestinal side effects, especially nausea and diarrhoea. All but one patient completed the course of chemotherapy. In terms of other adverse effects, one patient required a dose reduction of irinotecan for asthenia and one required a dose reduction of thalidomide because of somnolence.
The researchers comment that the main dose-limiting factor of irinotecan is gastrointestinal toxic effects, especially diarrhoea, which can be early or late onset. Late-onset diarrhoea is more common, occurring in most patients. It is severe in up to 40 per cent of patients and can lead to hospital admission, dose alteration or interruption of chemotherapy.
They say that the mechanism by which thalidomide eliminates the gastrointestinal effects of irinotecan is unclear. A phase II trial has been started to assess the therapeutic efficacy of the combination, the authors add (Lancet 2000:356:566).