Smectite for Chemotherapy-Induced Diarrhea in Dogs

In the Literature

Fournier Q, Serra JC, Williams C, Bavcar S. Chemotherapy-induced diarrhoea in dogs and its management with smectite: results of a monocentric open-label randomized clinical trial. Vet Comp Oncol. 2021;19(1):25-33.

The Research …

Chemotherapy-induced diarrhea (CID) is an adverse effect that can result in treatment alteration.¹ The incidence of CID is unknown, and there is no consensus on treatment.^1,2 CID is often treated with metronidazole¹; however, metronidazole can negatively affect the gut microbiome, and the benefits for treating CID are largely unknown.³ Smectite is an activated, natural aluminosilicate clay that has multiple proposed benefits (eg, adsorption of water, strengthened mucosal barrier, stabilized intestinal microbiome).^4-6

This prospective, randomized, placebo-controlled clinical trial aimed to assess the efficacy of smectite for treatment of CID and collect epidemiologic data on CID in dogs. Sixty dogs with a confirmed diagnosis of neoplasia and that were receiving chemotherapy were randomly placed into 2 treatment groups. Group 1 received smectite (0.5 g/kg PO divided into 2-3 doses every 24 hours) for CID, and group 2 received no treatment for CID. Dogs with pre-existing diarrhea and those with GI tumors were excluded. Rescue metronidazole was prescribed for protracted diarrhea in both groups. No dietary changes were allowed for the duration of the study. 

The number of diarrhea events between the  groups was similar (group 1, 54 events; group 2, 56 events). Median time to resolution of diarrhea for group 1 (19.5 hours) was significantly shorter than for group 2 (53 hours). Rescue metronidazole was also prescribed significantly less frequently in group 1 (5 of 54 events) than in group 2 (40 of 56 events). 

A median of 2 smectite doses were administered to group 1 before resolution of diarrhea, and a median of 6 rescue metronidazole doses were given to group 2 before resolution of diarrhea (median time, 64 hours). More dogs in group 2 (n = 10) than in group 1 (n = 3) had continuous diarrhea that resulted in hospitalization, chemotherapy discontinuation, or dose adjustments. These results support the administration of smectite as first-line management of CID in dogs.

… The Takeaways

Key pearls to put into practice:

• Smectite (0.5 g/kg PO divided into 2-3 doses every 24 hours) was associated with more rapid resolution of CID.

• This study found that CID was rapidly self-resolving in 28.5% of diarrhea events in the untreated control group, and time to resolution after metronidazole was started was prolonged (median, 64 hours). These findings, coupled with the potential for metronidazole disruption of the GI microbiome,³ challenge whether metronidazole treatment of CID is beneficial.

• Overall incidence of CID was relatively low (25.8%). In this study, doxorubicin and vinca alkaloid agents were associated with a higher incidence of CID than cyclophosphamide, carboplatin, and other agents.

• CID occurred in subsequent administrations of the same chemotherapeutic drug in only 43.4% of events; as such, chemotherapy dose adjustments for CID may not be particularly beneficial.