Page 320 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

298 PART III Therapeutic Modalities for the Cancer Patient

that achieved with 30 Gy in 10 fractions in patients with painful formulations for patients that have oral mucositis without clear
bone metastases. 184 evidence of a superimposed bacterial infection. 202
In veterinary medicine the use of RT for palliation of patients
VetBooks.ir with malignant osteolytic bone pain has been reported in several Pharmacologic Desensitization Strategy
185–187
and
diseases, including feline oral squamous cell carcinoma
canine oral melanoma. 188–193 The best studied use of RT for pain Many of the aforementioned treatments have been formulated to
control is palliation of canine appendicular OSA. Interestingly, target both peripheral and central mechanisms, mainly designed
Weinstein and collaborators 194 demonstrated that a single fraction as long-term therapies. However, a large number of cancer
of 8 Gy failed to measurably reduce lameness in dogs with appen- patients must undergo surgical procedures that can exacerbate
dicular OSA. However, a subset of those dogs did have improved the signs of pain. In this context the perioperative management
limb function and, in a separate study, 91% of dogs experienced of pain is a critical step in avoiding upregulation of peripheral
clinically appreciable analgesia after delivery of 16 Gy in two con- and central components that contribute to pain hypersensitivity
secutive daily fractions of 8 Gy. 195 Higher doses of radiation have syndromes. 203–205 Meta-analyses have been performed to evaluate
been investigated in other studies. Although dissimilar methodol- the efficacy of various systemically administered drugs for the pre-
ogy precludes direct comparison, results are similar with response vention of chronic pain after soft tissue surgery in human adults.
rates up to 92%, median time to onset of pain relief ranging from The most common pharmacologic interventions include periop-
2 to 14 days, and median duration of pain relief ranging from 67 erative use of oral gabapentin, pregabalin, mexiletine, venlafaxine,
to 95 days. 195,196 Unfortunately, the lack of both proper controls, NSAIDs, and IV steroids, ketamine, fentanyl, and lidocaine. 206
and failure to use validated objective measures of cancer pain make In veterinary medicine a multimodal approach is most often
complete and reliable interpretation of these studies challenging. applied in small animal medicine, with apparent improvement
in acute postoperative pain. 207–214 Fentanyl, hydromorphone,
Analgesia for Radiation Side Effects morphine, medetomidine, ketamine, and lidocaine are the most
common drug infusions used both intraoperatively and postop-
Whereas palliative-intent RT can be used to relieve cancer pain, eratively (Table 16.6); however, no study has evaluated the effect
definitive-intent RT can itself result in painful side effects. RAP of such an approach on the incidence, severity, and/or character
can result from acute or late radiation side effects. Although late of chronic pain after surgery (whether associated with nociceptive,
side effects can be quite severe, they are also relatively uncommon. neuropathic, or cancer pain).
Thus the most commonly encountered forms of RAP occur dur-
ing and shortly after a course of RT. Acupuncture
As mentioned previously, painful RT side effects are common
in dogs but less common in cats. Canine RAP is often associated Acupuncture can be provided through simple needle placement or
with grade II or higher RT-induced dermatitis or oral mucositis, by needle placement combined with electrical stimulation (of high
which is characterized by moist desquamation and edema. In a or low frequency, although most types of pain respond to low-
prospective study of 80 dogs undergoing RT for head and neck frequency stimulation). Results of a study in normal experimental
cancer, 80% of dogs undergoing definitive-intent RT developed dogs demonstrated a weak analgesic effect of electroacupuncture
grade II radiation-induced mucositis, with 44% progressing to in anesthetized patients, as evaluated by a reduction in the mini-
grade III lesions. 22 mum alveolar concentration of an inhaled anesthetic agent. 215
The treatment of RAP is empirical. Whereas many dogs with Recent data from a rodent model suggests that electroacupuncture
RAP once were treated with glucocorticoids, practice patterns may have beneficial effects in the treatment of pain associated with
have shifted, and patients with non–round cell neoplasms that bone cancer. 216,217 As yet, no evidence indicates that acupuncture
have RAP now often are managed with NSAIDs instead. This is provides pain relief in veterinary patients, but the authors do
due in part to the expectation of enhanced analgesia, but it is also encourage its use along with known analgesics.
influenced by the hope for additive antineoplastic effects. 197–199
Other systemic and topical therapies are frequently used; complete Future Analgesic Therapies
discussion of this topic is beyond the scope of this chapter but
has been summarized elsewhere. 200 Because that review focused Over the past few years, evidence has shown that the pain trans-
on management of radiation-induced dermatitis, it is also worth mission system is plastic (i.e., it alters in response to inputs). This
noting that some veterinary radiation oncologists use “magic plasticity results in a unique neurobiologic signature within the
mouthwash” to manage radiation-induced oral mucositis. Magic PNS and CNS for each painful disease. Understanding the indi-
mouthwash is a term used to describe lidocaine-based rinses. Sev- vidual neurobiologic signatures for different disease processes
eral formulations are used in clinical practice, and many include should allow novel, targeted, and more effective treatments to
ingredients such as diphenhydramine, corticosteroids, antifun- be established. 218 This approach should also allow for a more
gals, and antibiotics. In a recent phase III clinical trial, the sever- informed choice to be made on which of the currently available
ity of RAP was significantly lower in humans with oral mucositis drugs might be most effective.
that had been treated with magic mouthwash versus placebo. 201 Several new approaches to pain treatment revolve around the
The methods included a rinse and spit technique. Unfortunately, use of mechanisms to destroy or “exhaust” neurons involved in
rinsing and gargling cannot be used in dogs. Thus it is unclear pain transmission. One approach is to use targeted neurotoxins
whether there is sufficient distribution or contact time to promote to cause neuronal death. 219 An example of this is the combination
a clinically advantageous effect in dogs with oral mucositis. Fur- of a neurotoxin (saponin) and a conjugate of substance P, called
thermore, because of the risk of promoting multidrug-resistant substance P saporin (SP-SAP). Substance P binds to the neuroki-
infections via exposure to prophylactic antibiotics, clinicians nin receptor (NKR), and the conjugate is internalized (a normal
are strongly cautioned against prescribing antibiotic-containing phenomenon of the receptor-ligand interaction), resulting in cell