Gastrointestinal toxicity may be acute (within 24 hours of chemotherapy administration) or delayed (>24 hours after chemotherapy).
Acute gi toxicity (typically emesis) is due to direct irritation of the chemoreceptor trigger zone or free radical stimulation
of enterochromaffin cells to release serotonin, which stimulates the CRTZ via vagal afferents. The mechanism of delayed gastrointestinal
toxicity is not as well understood, but due to injury to dividing gastrointestinal epithelial cells. Vomiting, diarrhea,
lethargy, and loss of appetite are noted. In cats, the most common toxicity is anorexia. Delayed gi toxicity usually resolves
in 2-3 days with supportive care.
*Vincristine is associated with a unique gi toxicity – paralytic ileus.
#Doxorubicin is associated with a unique gi toxicity – hemorrhagic colitis.
Prevention of Gastrointestinal Toxicity
1. Give appropriate doses of chemotherapy, diluted appropriately, and at the appropriate rate.
2. Reduce dose by 20-25% if significant gi toxicity.
3. Prophylactic antiemetic therapy is recommended for patients receiving emetogenic agents or with previous emesis/nausea
following a drug.
a. Maropitant citrate (Cerenia) – substance P/neurokinin type 1 (NK-1) receptor antagonist – blocks central and peripheral
activation of the emetic center. Dose in dogs only: 1 mg/kg SC 1 hour before chemotherapy agent. May sting. Only antiemetic
licensed for dogs. No information available about use in cats. In humans, it is recommended that NK-1 antagonists be used
with 5-HT3 antagonists.
b. Dolasetron and ondansetron (Anzemet and Zofran) – serotonin/5-hydroxytryptamine 3 (5-HT3) receptor antagonists – block
receptors in gi tract and CRTZ. Give immediately before administration of chemotherapy if IV, 30 minutes prior if oral.
Dolasetron (dogs/cats): 0.6-1 mg/kg IV slowly. Ondansetron (dogs): 0.1-1 mg/kg IV slowly or PO, (cats): 0.1-0.15 mg/kg IV
slowly 15 minute before chemotherapy.
c. Metoclopramide (Reglan): dopamine (D2) receptor antagonist, 5-HT3 receptor antagonist, increases tone at lower esophageal
sphincter and increases gastric emptying. 0.2-0.5 mg/kg PO or SC q8 hours at least 30 minutes before treatment. This drug
is used for less emetogenic agents and patients may be sent home on this drug orally.
d. Butorphanol: mu opioid receptor antagonist, suspected to act at vomiting center. Has been used in dogs before cisplatin
and streptozotocin at 0.2-0.4 mg/kg IM 20 minutes before administration.
Treatment of Gastrointestinal Toxicity
2. If the patient is acting normal and has self-limiting vomiting: water trial then bland diet trial. Consider metoclopramide
0.2-0.5 mg/kg PO q8 hours for nausea. (Maropitant citrate is also available as tablets for oral administration, but has not
been evaluated for this use.)
3. If the patient is acting normal and has diarrhea that is not bloody or watery: bland diet, consider metronidazole 15 mg/kg
PO q12 hours for colitis.