With the intent of increasing therapeutic effectiveness, palliative radiation therapy can be combined with other adjuvant
treatments such as oral prednisone or systemic cytotoxic chemotherapy. In one recent study, 35 dogs with nonresectable cutaneous
mast cell tumors were treated with oral prednisone and palliative radiation therapy.32 This palliative treatment protocol provided an impressive overall response rate of 88.5%, with 12 complete responses and
19 partial responses. In addition to the high response rate, the median progression-free survival time of treated dogs was
1,031 days.
Radiation therapy, either curative-intent or palliative, to treat nonresectable cutaneous mast cell tumors should be considered
a viable treatment option in dogs. Although most dogs will ultimately experience local tumor recurrence or distant metastasis,
reasonably long median survival times appear to be achievable. Combining radiation therapy with other systemic adjuvant treatments
such as oral prednisone or chemotherapy may provide beneficial additive effects, further improving quality-of-life scores
and survival times in dogs with macroscopic tumor burdens.
Intralesional triamcinolone
Corticosteroids are often used to treat cutaneous mast cell tumors, either as single agents or preferably in combination with
other adjuvant therapies. The direct injection of the long-acting corticosteroid triamcinolone into cutaneous mast cell tumors
has been anecdotally reported to be an effective treatment option (Figure 8). Biologically, the reduction in mast cell tumor size subsequent to intralesional corticosteroid administration may be attributed
to reduced peritumoral inflammation and swelling, as well as a direct cytolytic effect on neoplastic mast cells.
Because of the lack of controlled clinical trials evaluating the efficacy of specific intralesional protocols, dosing regimens
may vary widely among veterinary practitioners. Anecdotally reported protocols include injecting 1 mg triamcinolone for every
centimeter of the tumor's diameter every 14 days and injecting a systemic dose of triamcinolone (0.22 mg/kg) uniformly into
the tumor every two or three weeks.
Intralesional corticosteroid administration is an easy and cost-effective means to reduce measurable tumor burden. It is best
suited for relatively small mast cell tumors and should be considered a treatment option to reduce the size of localized tumors
before definitive surgical resection. In addition to serving as a neoadjuvant before curative surgery, intralesional therapy
may be useful as a palliative treatment option in small- to moderate-size tumors that are refractory to radiation therapy
or chemotherapy.
TARGETED THERAPIES
Mast cells grow and proliferate in response to specific cellular signals transduced by membrane-bound receptors, such as c-kit. Mutations in c-kit signaling can dysregulate cellular physiology, leading to the formation of a neoplastic population of mast cells. It has
been confirmed that some malignant mast cell tumors in dogs carry a mutation in the gene coding for the c-kit receptor, resulting in unregulated intracellular signaling, cell proliferation, and subsequent mast cell tumor formation.33,34
In laboratory experiments, indolinone derivatives capable of inhibiting constitutively activated c-kit mutants have shown promise in killing neoplastic mast cells in vitro.35 As a clinical corollary, one recent study evaluated the use of an indolinone derivative (SU11654) for treating spontaneous
canine cutaneous mast cell tumors.36 Study results demonstrate SU11654 to be well-tolerated and therapeutically effective. Of the 22 dogs with mast cell tumors
treated with SU11654, 50% experienced tumor shrinkage, with six patients achieving a complete remission. Although the findings
from this clinical study are extremely promising and could dramatically change the way we treat cancers such as cutaneous
mast cell tumors, additional prospective trials need to delineate the exact role of small molecule inhibitors, such as SU11654,
for treating cancer-bearing pets.
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