Coyle, V.M., Lungulescu, D., Toganel, C., Niculescu, A., Pop, S., Ciuleanu, T., … Wilson, R.H. (2013). A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea. British Journal of Cancer, 108, 1027–1033.

To examine the effectiveness of the use of a controlled-release transdermal patch preparation of mecamylamine (AG1004)

Patients who had received at least one cycle of chemotherapy and experienced grade 1 or 2 diarrhea were randomized to receive transdermal mecamylamine (AG1004) 4 mg every 24 hours or placebo using an identical-looking patch. The patch was applied 24 hours prior to chemotherapy and reapplied daily for the duration of the treatment cycle. Patients were allowed to use loperamide, codeine phosphate, or octreotide on a rescue basis for any active episodes of diarrhea. During the next cycle, the AG1004 dose was increased to 8 mg per day. Evaluation was done at the end of the first day of each cycle and at the end of the overall cycle of chemotherapy. Daily logs were used to record bowel movements and use of rescue medication.

• The study reported on 64 patients.
• Mean age was 61.2 years with a range of 35–88 years.
• The sample was 25% male and 75% female.
• Patients had various tumor types, with colon and breast cancer most common.
• All patients were receiving chemotherapy that has been associated with diarrhea, and all had experienced diarrhea in a previous cycle.
• Patients were being treated with fluorouracil (5-FU), capecitabine, or irinotecan.

This was a multisite, outpatient study conducted in the United Kingdom and Romania.

• All patients were undergoing the active treatment phase of care.
• This study has clinical applicability for elder care.

This was a double-blind, randomized, placebo-controlled study.

• The Bristol stool scale and the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) grading were used.
• Patients kept daily diaries of bowel movements and use of rescue medication.

• Overall compliance with treatment was an average of 90% in both study groups.
• Overall response (OR) was 1.26 in favor of the treatment, based on physician assessment, but this was not statistically significant.
• Based on patient reporting of four or fewer bowel movements per day from diaries, more patients were classified as responders in the treatment group (OR = 6.4, 95% confidence interval [CI] = 1.7–24.6, p = 0.05). 
• Use of rescue medication was low in both groups. 
• Overall use of loperamide was less in the treatment arm at both treatment dosages, with a greater trend observed with the 8-mg dose level (p = 0.05).
• No differences were found between groups in other associated gastrointestinal symptoms.

AG1004 was associated with less diarrhea compared to placebo on day one of chemotherapy cycles and did not appear to have significant adverse effects. AG1004 may be helpful in preventing chemotherapy-induced diarrhea.

The sample size was small with fewer than 100 participants.

This study demonstrated some promising results, suggesting that treatment with AG1004 may be useful in preventing chemotherapy-induced diarrhea in patients being treated for cancer with agents known to be associated with diarrhea. Further research is warranted to confirm these findings.