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Clinical Trial
. 2013 Mar 19;108(5):1027-33.
doi: 10.1038/bjc.2013.35. Epub 2013 Mar 5.

A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea

V M Coyle  1 , D Lungulescu, C Toganel, A Niculescu, S Pop, T Ciuleanu, C Cebotaru, J Devane, M Martin, R H Wilson
Affiliations
Clinical Trial

A randomised double-blind placebo-controlled phase II study of AGI004 for control of chemotherapy-induced diarrhoea

V M Coyle et al. Br J Cancer. .

Abstract

Background: AGI004 is a controlled-release transdermal patch preparation of mecamylamine. We conducted a randomised placebo-controlled phase II study of two dose levels of AGI004 in chemotherapy-induced diarrhoea (CID).

Methods: Adult patients receiving chemotherapy who had experienced diarrhoea (NCI grade 1-2) during previous cycles of chemotherapy were eligible. In all, 64 patients were randomised to receive AGI004 4 mg then 8 mg per 24 h transdermal patch or placebo for two sequential cycles of chemotherapy. Patients' severity of diarrhoea was physician-assessed using NCI grade of diarrhoea and patient-assessed using information recorded in daily diaries of bowel movements.

Results: Overall AGI004 doubled the odds of a response to treatment on the first day of chemotherapy based on physician assessment of NCI grade of diarrhoea compared with placebo (odds ratio=2.0, 90% confidence interval: 0.9-4.5) and there was a trend to improved response rates for AGI004 for the full treatment cycle although these results were not statistically significant. There was also evidence of significantly improved response rates based on patient assessment of diarrhoea both overall (P=0.05) and at the 8-mg dose level (P=0.02) compared with placebo.

Conclusion: AGI004 demonstrated effectiveness in reducing chemotherapy-associated diarrhoea, with results suggesting response across multiple measurements of diarrhoea. Treatment was well tolerated with no drug-related adverse events. Further evaluation of this agent in the management of CID is warranted.

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References

    1. Barbounis V, Koumakis G, Vassilomanolakis M, Demiri M, Efremidis AP. Control of irinotecan-induced diarrhea by octreotide after loperamide failure. Support Care Cancer. 2001;9:258–260. - PubMed
    1. Benson AB, Ajani JA, Catalano RB, Engelking C, Kornblau SM, Martenson JA, McCallum R, Mitchell EP, O'Dorisio TM, Vokes EE, Wadler S. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol. 2004;22:2918–2926. - PubMed
    1. Boige V, Mendiboure J, Pignon JP, Loriot MA, Castaing M, Barrois M, Malka D, Tregouet DA, Bouche O, Le Corre D, Miran I, Mulot C, Ducreux M, Beaune P, Laurent-Puig P. Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05. J Clin Oncol. 2010;28:2556–2564. - PubMed
    1. Braun MS, Richman SD, Thompson L, Daly CL, Meade AM, Adlard JW, Allan JM, Parmar MK, Quirke P, Seymour MT. Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial. J Clin Oncol. 2009;27:5519–5528. - PubMed
    1. Cascinu S, Bichisao E, Amadori D, Silingardi V, Giordani P, Sansoni E, Luppi G, Catalano V, Agostinelli R, Catalano G. High-dose loperamide in the treatment of 5-fluorouracil-induced diarrhea in colorectal cancer patients. Support Care Cancer. 2000;8:65–67. - PubMed

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