Page 1309 - Small Animal Internal Medicine, 6th Edition

CHAPTER 77 Complications of Cancer Chemotherapy 1281

Acute anorexia, nausea, and vomiting caused by inject- products (Pepto-Bismol, 3-15 mL or 1-2 tabs PO q8-12h) are
able drugs are usually prevented by administering the offend- generally effective in controlling the clinical signs in dogs,
VetBooks.ir ing agents by slow IV infusion. If these problems persist which usually resolve in 3 to 5 days. The administration of
Pepto-Bismol from days 1 to 7 of the treatment may alleviate
despite this approach, antiemetics such as metoclopramide
can be given at a dosage of 0.1 to 0.3 mg/kg IV, subcutane-
(i.e., one of the breeds mentioned, a patient with a history of
ously, or PO every 8 hours. Other antiemetics effective in or prevent these signs in dogs at risk for gastroenterocolitis
dogs with chemotherapy-induced emesis are butorphanol this toxicity). The use of bismuth subsalicylate should be
(Torbugesic, Fort Dodge Labs, Fort Dodge, IA) at a dosage avoided in cats. Gastroenteritis associated with the PO
of 0.1 to 0.4 mg/kg intramuscularly or intravenously every 6 administration of methotrexate usually occurs after 2 weeks
to 8 hours; ondansetron (Zofran, GlaxoSmithKline, Research of administration; the treatment is the same as that used for
Triangle Park, NC) at a dosage of 0.1 to 0.3 mg/kg immedi- doxorubicin-induced enterocolitis.
ately before chemotherapy and every 6 hours thereafter; or
maropitant (Cerenia, Zoetis, Madison, NJ) at a dosage of
2 mg/kg, PO every 24 hours. (For additional information on HYPERSENSITIVITY REACTIONS
this subject, see Chapter 28.) Our preferred approach is to
use maropitant in these situations. Acute type I hypersensitivity reactions occasionally occur in
Methotrexate and cyclophosphamide, two drugs com- dogs receiving parenteral L-asparaginase or doxorubicin and
monly administered PO, can also cause anorexia, nausea, are common in dogs treated with IV etoposide or taxol
and vomiting. Methotrexate commonly causes anorexia and derivatives; in the latter two, there is a reaction to the solu-
vomiting 2 or 3 weeks after the start of therapy in dogs; bilizing agent (Tween 80, Cremophor EL). As discussed
these adverse effects are usually controlled with antiemet- earlier, a water-soluble form of etoposide is now available.
ics as described earlier. If these problems persist, it may The reaction to doxorubicin does not appear to be a true
be necessary to discontinue methotrexate treatment. hypersensitivity reaction, however, because this agent can
Cyclophosphamide tends to induce anorexia or vomiting induce direct mast cell degranulation independently of
in some cats. Cyproheptadine (Periactin, Merck Sharp & immunoglobulin E (IgE) mediation. Etoposide can be safely
Dohme, West Point, PA) at a dosage of 1 to 2 mg (total administered to dogs PO. Hypersensitivity reactions to anti-
dose) PO q8-12h is quite effective as an appetite stimulant cancer agents are extremely rare in cats and thus are not
and antinausea agent in cats; an alternative option is mir- discussed.
tazapine (3.75 mg PO q24h for cats; 3.75-30 mg PO q24h Clinical signs in dogs with hypersensitivity reactions to
for dogs). anticancer agents are similar to those in dogs with other
In our experience, chemotherapy-associated anorexia in types of hypersensitivity reactions (i.e., they are primarily
dogs is more difficult to manage because nonspecific appetite cutaneous and gastrointestinal). Typical signs appear during
stimulants such as cyproheptadine and mirtazapine do not or shortly after administration of the agent and include head
seem to be effective. In these cases, oral antiemetics can be shaking (caused by ear pruritus), generalized urticaria and
considered, mainly ondansetron and maropitant, which can erythema, restlessness, occasionally vomiting or diarrhea,
be beneficial to decrease the duration of anorexia in some and rarely collapse caused by hypotension.
dogs. The novel Entyce (capromorelin oral solution, Aratana Most systemic anaphylactic reactions can be prevented
Therapeutics, Leawood, KS) is also an appetite stimulant in by pretreating the patient with H 1 antihistamines (i.e.,
both dogs and cats with chemotherapy or cancer-induced intramuscular diphenhydramine, 1-2 mg/kg 20-30 minutes
anorexia (3 mg/kg PO q24h). before administration of the drug) and by administering
Gastroenterocolitis is uncommon in patients receiving certain drugs (e.g., L-asparaginase) subcutaneously or intra-
anticancer agents. Drugs that occasionally cause this include muscularly rather than through an IV route. If the agent
methotrexate, 5-FU, actinomycin D, and doxorubicin. It cannot be given by any other routes (i.e., doxorubicin), it
occurs rarely in association with other alkylating agents such should be diluted and administered by slow IV infusion.
as cyclophosphamide. Of the drugs mentioned in the previ- The treatment of acute hypersensitivity reactions includes
ous paragraphs, only doxorubicin and methotrexate appear immediate discontinuation of the agent and the adminis-
to be of clinical relevance. On the basis of the author’s experi- tration of H 1 antihistamines (i.e., diphenhydramine, 0.2-
ence, Collies and Collie crosses, Old English Sheepdogs, 0.5 mg/kg by slow IV infusion), dexamethasone sodium
Cocker Spaniels, and West Highland White Terriers appear phosphate (1-2 mg/kg IV), and fluids if necessary. If the
to be extremely susceptible to doxorubicin-induced entero- systemic reaction is severe, epinephrine (0.1-0.3 mL of a
colitis, independently of ABCB1 mutations. 1 : 1000 solution intramuscularly or intravenously) should
Doxorubicin-induced enterocolitis is characterized by the be used. Once the reaction subsides (and if it was mild),
development of hemorrhagic diarrhea (with or without vom- the administration of certain drugs such as doxorubicin
iting), primarily of large bowel type, 3 to 7 days after the may be continued. Injectable H 1 antihistamines should
administration of the drug; it is more common in dogs than be used with caution in cats (if at all) because they can
in cats. Supportive fluid therapy (if necessary) and treatment cause acute central nervous system depression leading
with therapeutic doses of bismuth subsalicylate–containing to apnea.