1. Depends on severity
2. Dexamethasone sodium phosphate 0.5 - 2 mg/kg IV
3. Diphenhydramine 1-2 mg/kg IM or slow IV (dog), IM only (cat)
4. Intravenous fluids at 90 ml/kg/hr (dog), 50 ml/kg/hr (cat)
5. Epinephrine if severe (Dilute 1 ml of 1:1,000 solution in 9 ml of 0.9% NaCl. Give 0.1 ml/kg of1:10,000 solution.)
Doxorubicin can cause an allergic-type reaction due to stimulation of mast cell degranulation during administration. Signs are similar
to those described for L-asparaginase. This is not a true allergic reaction.
1. Administer at appropriate rate - no faster than 1 mg/minute or over 10-15 minutes for small dogs or cats.
2. If allergic reaction with previous dose, premedicate patient with diphenhydramine 2 mg/kg IM and dexamethasone SP 0.5
mg/kg SQ 20-30 minutes prior to subsequent doses and administer at slower rate.
1. Stop infusion.
2. Reaction is usually not as severe as with L-asparaginase.
3. Dexamethasone sodium phosphate 0.5 - 2 mg/kg IV
4. Diphenhydramine 1-2 mg/kg IM or slow IV (dog), IM only (cat)
A unique cumulative toxicity of doxorubicin. Typically seen at doses of 180-240 mg/m2 . Free radical damage occurs because cardiac myocytes have less production of catalase. Initially results in cardiac arrhythmias
and decreased contractility. Progresses to dilative cardiomyopathy and congestive heart failure weeks to months after treatment.
1. Echocardiogram prior to doxorubicin for breeds at risk for DCM and dogs with cardiac abnormalities (heart murmur, arrhythmia,
cardiomegaly). Do not treat dogs with myocardial dysfunction.
2. Limit total lifetime cumulative dose to <180-240 mg/m2. Weigh risk versus benefit if giving >150 mg/m2 and echocardiogram
patients receiving further doses.
3. Substitute non-cardiac toxic agents (mitoxantrone, actinomycin-D) after 150 mg/m2.
4. Dexrazoxane (Zinecard) – 10 mg for every 1 mg of doxorubicin given IV <30 minutes before doxorubicin. Free radical scavenger,
not helpful once cardiac injury present. Not used routinely in veterinary oncology.
Do not administer further doxorubicin. Consult with cardiologist.
A unique toxicity of cyclophosphamide. Acrolein, a metabolite, causes direct injury to bladder urothelium.
1. Give furosemide (2 mg/kg PO, IV, or SC) with cyclophosphamide, reduces risk from 9% to 1%.
2. Give in morning to avoid acrolein in bladder overnight.
3. Give water ad lib and encourage frequent urination for 24 hours after cyclophosphamide.
4. If a dog develops hemorrhagic cystitis, cyclophosphamide should not be administered again. Often chlorambucil is substituted.
Urinalysis and culture and sensitivity to check for bacterial cystitis, treat if present. Hemorrhagic cystitis is self-limiting,
but may take weeks or months to resolve. Treat with NSAIDs or prednisone for anti-inflammatory and analgesic affects. Oxybutynin
hydrochloride (0.2 mg/kg PO q8-12 hours) has been recommended for straining and pollakiuria. Consult with oncologist.
Cats Are Not Small Dogs
1. ***Do not administer to cats***
a. Cisplatin - fatal pulmonary edema
b. 5-fluorouracil - fatal neurologic signs
2. Some toxicities are not observed clinically in cats
a. Cyclophosphamide – hemorrhagic cystitis
b. Doxorubicin - documented histopathologic changes, but cardiotoxicity is not seen clinically