Page 364 - Cote clinical veterinary advisor dogs and cats 4th

Chemotherapy: Adverse Events 153

• Hepatotoxicosis (lomustine, toceranib, infection, usually by gram-negative GI 10% solution with 6 mL sterile water for
vinorelbine, rabacfosadine, rare idiosyncratic • Cardiotoxicosis: doxorubicin: multiple; reac- injection) divided between the displaced
flora.
VetBooks.ir • Nonspecific muscle pain (toceranib) tive oxygen species and toxic metabolites extravasation site. Repeat hours later. E-collar, Diseases and Disorders
IV catheter and in pincushion fashion into
reactions with others)
wound management as needed
• Pulmonary fibrosis (rabacfosadine, rare: some
cause intracellular damage, apoptosis, and
alkylating agents)
cardiomyopathy (DCM) weeks-months after
• Dermatologic toxicosis (rabacfosadine) myocardial cell death; irreversible dilated • Acute vomiting: stop administration; anti-
emetic therapy (see below); IV fluid support
treatment; typically in dogs at cumulative if indicated
HISTORY, CHIEF COMPLAINT doses ≥ 180-240 mg/m . Delayed AEs:
2
• Chemotherapeutic agent administered within • Hemorrhagic cystitis: cyclophosphamide • GI: usually resolves in 2-3 days
appropriate time frame to expect AE metabolite injures urothelium ○ Patient normal, decreased appetite:
• Presenting/historical signs vary with AEs • Nephrotoxicosis: cisplatin: tubular injury, maropitant citrate 1-2 mg/kg (dog), 1 mg/
○ Allergic: facial swelling, erythema, urti- decreased glomerular filtration rate; toceranib: kg (cat) PO q 24h, tempting food. For
caria, vomiting, or collapse during/within renal protein loss, azotemia, hypertension due cats, mirtazapine 3.75 mg/CAT q 72h.
hours of treatment to glomerular and tubular epithelium effects Capromelin is new alternative appetite
○ Extravasation injury: irritation at infusion • Hepatotoxicosis: lomustine: hepatocellular stimulant for dogs and cats. If mild
site hours to 14 days after chemotherapy and ductal epithelial injury with inflamma- vomiting, antiemetic, NPO, then water
○ GI toxicosis: vomiting, diarrhea, lethargy, tion and cholestasis, eventually cirrhosis and bland diet trial (pp. 67, 1040, and
anorexia, 2-5 days after chemotherapy • Toceranib AE: tyrosine kinase inhibition 1199)
○ Myelosuppression: usually none; possible: ○ Patient normal, mild diarrhea: bland diet,
lethargy, inappetence, typically 7-14 days DIAGNOSIS consider metronidazole 15 mg/kg PO q
after chemotherapy 12h for colitis
○ Ileus: inappetence, lethargy, abdominal Diagnostic Overview ○ Patient lethargic, vomiting/diarrhea
discomfort, vomiting, constipation AEs of chemotherapy are suspected based on persistent or watery/bloody: hospitalize
○ Cardiotoxicosis: often none; possible: characteristic signs and timing after the drugs for supportive care:
exercise intolerance, tachypnea, weakness, are administered, and diagnosis is supported ■ Intravenous fluids
collapse by resolution and lack of recurrence with dose ■ Antiemetic (e.g., maropitant citrate
○ Hemorrhagic cystitis: stranguria, pol- delay, reduction, or substitution. 1 mg/kg IV q 24h; if refractory, add
lakiuria, hematuria, incontinence ondansetron 0.5-1 mg/kg IV slowly q
○ Nephrotoxicosis: often none; possible: Differential Diagnosis 12h [dog] or 0.1-0.5 mg/kg IV slowly
polyuria and polydipsia (PU/PD), lethargy, Exacerbation of neoplastic disease, paraneo- q 6-12h [cat]); for vincristine-induced
inappetence plastic syndromes, unrelated diseases ileus, metoclopramide 1.1-2.2 mg/kg/
○ Hepatotoxicosis: often none; possible: day IV CRI.
lethargy, inappetence, vomiting, diarrhea, Initial Database ■ Gastric acid reduction: pantoprazole
icterus • CBC +/− serum biochemistry profile, 1 mg/kg IV slowly q 12-24h
○ Dermatoxicosis: otitis, pruritic alopecic urinalysis ■ Antibiotic therapy if bloody vomit/
lesions, dorsal distribution • Additional tests determined by history, exam, diarrhea, neutropenia, fever
○ Pulmonary fibrosis: exercise intolerance, and preliminary diagnostic results ■ Nutritional support
dyspnea, tachypnea, cough • Myelosuppression: usually none required;
TREATMENT counts normalize within 2-3 days (potentially
PHYSICAL EXAM FINDINGS prolonged with carboplatin and lomustine
• Allergic reactions during/within hours of Treatment Overview [cats]).
treatment (p. 54) Goals are resolution of AEs and prevention of ○ If neutrophil count < 1000 cells/mcL,
• Extravasation injury: irritation at site hours complications. prophylactic antibiotics for 3-7 days (dogs
to 14 days after treatment, can progress to only): enrofloxacin 10 mg/kg PO q 24h
slough of skin and subcutis Acute General Treatment or amoxicillin/clavulanate 20 mg/kg PO q
• Cardiotoxicosis: often none; possible arrhyth- AEs during administration: 12h or sulfadiazine-trimethoprim 15 mg/
mia, tachycardia, pulse deficits, new murmur, • First step: discontinue administration. kg PO q 12h
tachypnea, dyspnea (p. 408) • Allergic reactions: diphenhydramine 2 mg/kg ○ If febrile/ill, hospitalize for intravenous
• Nephrotoxicosis: often none; possible weight IM and dexamethasone sodium phosphate fluids and antibiotics. Empirical treatment:
loss, dehydration (SP) 0.2-0.5 mg/kg IV. If indicated, intra- ampicillin or ampicillin/sulbactam 22 mg/
• Hepatotoxicosis: often none; possible weight venous fluids 90 mL/kg/h (dog, initial bolus kg IV q 8h, with enrofloxacin 5 mg/kg
loss, icterus of 30 mL/kg) or 50 mL/kg/h (cat, initial (cats) or 10 mg/kg (dogs), dilute and give
• Dermatoxicosis: otitis, alopecic pinnae, bolus of 15 mL/kg); if severe, epinephrine slowly IV q 24h
pruritic alopecia, ulcerations, excoriations 0.1 mL/kg of 1 : 10,000 or 0.01 mL/kg of Unique AEs:
on dorsum; possibly painful 1 : 1000 solution IV • Cardiotoxicosis: discontinue doxorubicin;
• Pulmonary fibrosis: dyspnea, tachypnea, • Extravasation injury: aspirate back before manage cardiac disease (pp. 263, 408, and
cyanosis, syncope, possible crackles removing catheter. Cold compress for all 1033)
drugs (except for vinca alkaloids [warm]) • Hemorrhagic cystitis: often self-limiting
Etiology and Pathophysiology 10 minutes q 6h for 72 hours. There (weeks-months); permanent damage possible.
• Allergic reactions: L-asparaginase: type I hyper- is limited information about antidotes/ Treat bacterial cystitis, if present; antiinflam-
sensitivity; doxorubicin: mast cell degranulation treatments. For vinca alkaloids, infuse 1 mL matory (nonsteroidal or prednisolone),
• Extravasation injury: multiple mechanisms 1% hyaluronidase SQ at extravasation site for analgesic (gabapentin 10 mg/kg q 8-12h or an
• Acute vomiting: chemoreceptor trigger zone each mL leaked. For doxorubicin, administer opioid); consult with oncologist if refractory
2
irritation dexrazoxane 400-600 mg/m IV in a dif- • Nephrotoxicosis: discontinue drug. If uremia,
• GI toxicosis: epithelial injury ferent vein within 3 hours of extravasation; oliguria, and/or anuria (p. 23). Proteinuria:
• Myelosuppression/febrile neutropenia: repeat at 24 and 48 hours. For dacarbazine may need to discontinue drug; angiotensin-
injury to proliferating hematopoietic cells. or mechlorethamine, inject 5 mL of 0.16 M converting enzyme (ACE) inhibitor (e.g.,
Severe neutropenia can allow opportunistic sodium thiosulfate (4 mL sodium thiosulfate benazepril 0.5 mg/kg q 12-24h), renal diet,
www.ExpertConsult.com