Page 1310 - Small Animal Internal Medicine, 6th Edition

1282 PART XII Oncology

DERMATOLOGIC TOXICITY 16 weeks. If perivascular administration of doxorubicin has
occurred (and the clinician has recognized it during or
VetBooks.ir It is rare for anticancer agents to cause dermatologic toxic- immediately after the administration), dexrazoxane (Zine-
card, Pfizer) can be administered at 5 to 10 times the dose
ity in small animals. However, three types of dermatologic
toxicities can occur: local tissue necrosis (caused by extrava-
mg of dexrazoxane should be given). Dexrazoxane is rather
sation), delayed hair growth and alopecia, and hyperpigmen- of doxorubicin given (i.e., for 30 mg of doxorubicin, 150-300
tation. More recently, the newest chemotherapeutic agent expensive, so it is not routinely used in small animal patients.
that is conditionally approved for use in dogs with lym- One of the authors has evaluated carvedilol (Coreg, Glaxo-
phoma, rabacfosadine (Tanovea, VetDC, Fort Collins, CO) SmithKline) in a limited number of dogs that received peri-
has been reported to have a unique dermatologic toxicity vascular doxorubicin. In three dogs that received treatment
discussed later. immediately after drug extravasation (at a dosage of
Local tissue necrosis resulting from the extravasation of 0.1-0.4 mg/kg q12-24h), there were no visible signs of necro-
vincristine, vinblastine, actinomycin D, doxorubicin, or sis. In three dogs that developed necrosis after perivascular
Tanovea is occasionally seen in dogs receiving these drugs doxorubicin administration, carvedilol resulted in rapid
but is extremely rare in cats. Indeed, according to anecdotal healing of the area (i.e., within 2-3 weeks). Clinical signs of
reports, cats have accidentally received full doses of doxoru- extravasation include pain, pruritus, erythema, moist der-
bicin perivascularly without developing tissue necrosis. The matitis, and necrosis of the affected area; severe tissue
pathogenesis of this toxicity is poorly understood, but it is sloughing may occur (Fig. 77.3). If local tissue reactions
thought to be mediated by release of free radicals. Every develop, they can be treated as shown in Box 77.1.
effort should be made to ensure that these drugs are admin- In dogs and cats undergoing chemotherapy, delayed hair
istered intravascularly. In addition to this complication, growth is more common than alopecia. This is in contrast to
some retrievers (e.g., Labrador and Golden Retrievers) the situation in human patients, in whom severe scalp alo-
appear to experience pruritus or discomfort around the site pecia is a predictable complication of therapy. Because most
of the IV injection even when the drug is known to have chemotherapeutic agents affect rapidly dividing tissues, cells
been administered intravascularly. This pain and discomfort in the anagen (growth) phase of the hair cycle are usually
frequently lead to licking and the development of a pyotrau- affected. Therefore hair is slow to regrow in areas that were
matic dermatitis (“hot spot”) within hours of the injection. clipped or shaved before or during chemotherapy. Excessive
In these dogs, applying a bandage over the injection site or shedding is also common.
placing an Elizabethan collar prevents this type of reaction. Alopecia occurs predominantly in woolly-haired (coarse-
To prevent or minimize the probability of extravascular haired) dogs such as Poodles, Schnauzers, and Kerry Blue
injection of caustic drugs, they should be administered
through small-gauge (22- to 23-gauge), indwelling, IV, over-
the-needle catheters or through 23- to 25-gauge butterfly
catheters. We use the former to administer doxorubicin and
the latter to administer the vinca alkaloids and actinomycin
D. Caustic drugs should be properly diluted before admin-
istration (i.e., vincristine to a final concentration of 0.1 mg/
mL and doxorubicin to a concentration of 0.5 mg/mL) and
the patency of the intravascular injection site ensured by
intermittently aspirating until blood appears in the catheter.
In the authors’ clinics, doxorubicin is not administered by
IV constant-rate infusion because such patients are more
likely to undergo extravasation. If the site is not patent, the
catheter should be placed in another vein. Recommenda-
tions for the management of extravascular injections are
controversial; other than cold-packing the area for a few
days, authors cannot agree as to whether diluting the extrav-
asated drug with saline solution is a good or bad idea. For
the management of perivascular doxorubicin, see next
paragraph.
If, despite these precautions, a local tissue reaction occurs,
it develops approximately 1 to 7 days after the perivascular
injection of vinca alkaloids or actinomycin D and 7 to 15
days after doxorubicin extravasation. Tissue necrosis result-
ing from doxorubicin extravasation is far more severe than FIG 77.3
that associated with the extravasation of other agents because Tissue necrosis after extravascular injection of doxorubicin
the drug is extremely caustic and persists in tissues for up to in a dog. Note the full-thickness sloughing of the area.