Page 496 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

474 PART IV Specific Malignancies in the Small Animal Patient

have shown that there is a survival advantage associated with treat- treatment groups at 742 days. 600 Radiation protocols, treatment
ment of progressive disease in dogs with AGASAC. 605,606,612,637 intent, and tumor stage were not described. 600 In the only report
of standardized curative-intent adjuvant RT, the MST of 15 dogs
Therefore excision of recurrent tumors or progressive nodal metas-
VetBooks.ir tasis is recommended, especially when it can be done with low was 956 days. 609 Dogs received 15 daily fractions of 3.2 Gy (total
dose of 48 Gy) to the primary site and regional LN beds using
morbidity. Although surgery rarely has a role in the management
of distant metastatic disease, particularly at the time of diagnosis, a nonconformal technique in combination with mitoxantrone
splenectomy may be considered in dogs with splenic metastasis in chemotherapy. Although STs were favorable, late complications
the context of slowly progressive disease when there is no evidence developed in half of the dogs. 609 Subsequent radiation toxicity
of metastasis to other distant sites. 607 studies showed that late radiation effects such as rectal stricture,
The roles for adjuvant chemotherapy and RT are controver- rectal perforation, and chronic colitis are more likely to occur
sial and not fully defined. Chemotherapy has traditionally been when radiation doses per fraction of 3 Gy or greater are used. 641,642
recommended for the treatment of canine AGASAC because of Therefore future curative-intent protocols should include pel-
the risk of metastasis. Drugs with demonstrated antitumor activ- vic irradiation at doses less than 3 Gy per fraction. 641,642 Use of
ity in the gross disease setting include carboplatin, cisplatin, and conformal radiation technology, such as intensity-modulated RT,
actinomycin D. 594,598,599 Other drugs reported in the postopera- should further reduce the risk of toxicity by optimizing avoidance
tive setting include mitoxantrone and melphalan. 564,609 However, of critical structures. Dose-dependent, self-limiting acute effects
no controlled study has shown a survival advantage with the use reported in the study of nonconformal curative-intent irradiation
of adjuvant chemotherapy in dogs with AGASAC. 600,601,605,606 In of this region included mild to severe moist desquamation of the
one study of 113 dogs with AGASAC, there was no significant perianal area and colitis resulting in perianal discomfort lasting 1
difference in outcome between dogs treated with surgery alone to 4 weeks. 609,642
and dogs treated with surgery and chemotherapy, with MSTs of The role of palliative-intent RT for relief of clinical signs associ-
500 days and 540 days, respectively. 600 Similarly, in another study ated with bulky AGASAC is better defined. Various hypofraction-
of 74 dogs, there was no significant difference in either MST or ated protocols have been described including 5 daily fractions of 4
time to progression for dogs treated with surgery alone (581 days Gy, 3 to 4 weekly fractions of 6 to 9 Gy, 8 fractions of 3.8 Gy on
and 402 days, respectively) and surgery and carboplatin (723 days a Monday–Wednesday–Friday schedule, and 5 biweekly fractions
and 384 days, respectively). 606 In fact, in another study, the use of 5 Gy. 601,611,617,640 These palliative RT protocols resulted in an
of adjuvant chemotherapy had a negative effect on DFI and no improvement in clinical signs in up to 63% of dogs, including
effect on ST. 605 In these retrospective studies, it is possible che- resolution of obstipation in some dogs. 611,617,640 Hypercalcemia
motherapy was more often offered or chosen in patients with resolved with RT alone in 31% of dogs and in an additional 46%
more advanced disease, which could have resulted in a bias against of dogs when RT was combined with prednisone and a bisphos-
chemotherapy effectiveness. Until controlled clinical trials are per- phonate. 617,640 The reported median progression-free intervals
formed to definitively define the role of chemotherapy in the man- (PFIs) for dogs treated with palliative-intent hypofractionated
agement of dogs with AGASAC, there is little evidence to support protocols were 10 to 11 months, and MSTs ranged from 8 to 15
its use in the adjuvant setting. months. 601,611,617,640 Acute effects were mild and infrequent with
Toceranib has been associated with modest tumor responses grade I–II acute colitis in 8% to 27% of dogs, and grade I–II
in canine AGASAC. 638 In a retrospective study of 32 dogs with acute skin effects in 17% to 21% of dogs. 611,617 Late effects were
multiple prior failed therapies, use of toceranib resulted in tumor rare in one study and included suspected rectal stricture in 3% of
response durations of 10 to 47 weeks. 638 A 25% partial response dogs and grade I late skin effects in 6% of dogs; these occurred
rate was noted and an additional 63% of dogs maintained stable in dogs treated with fractions of 5 Gy or greater. 617 In contrast,
disease, for a total clinical benefit rate of 88%. Resolution of hyper- late effects were not observed in dogs treated with 8 fractions of
calcemia has also been reported with toceranib treatment. 638 The 3.8 Gy delivered on a Monday–Wednesday–Friday schedule. 611
antitumor effect of toceranib may be mediated through inhibition Severely hypofractionated RT should be used cautiously because
of the PDGFR-β or vascular endothelial growth factor receptor late effects, such as rectal stricture, rectal perforation and chronic
2, both of which are expressed in canine AGASAC. 628,629 Con- colitis, are related to dose per fraction. 611,617,641,642
trolled clinical trials are needed to determine the role of toceranib When interpreting the results of RT studies, it is impor-
in the treatment of dogs with AGASAC. COX-2 is expressed in tant to consider that tumor control probability and risk of RT
the glandular epithelial cells of AGASAC, 626 and this may suggest complications are affected by radiation dose distributions in
a potential role for COX-2 inhibitors in the management of dogs the patient. A radiation treatment planning study showed that
with AGASAC. Adjuvant electrochemotherapy using cisplatin has computerized, CT-based, 3-D conformal RT planning results
been reported in a single dog after an incomplete primary tumor in improved radiation dose distributions, with greater dose
excision. 639 homogeneity in neoplastic tissues and better control of expo-
RT has been described for both palliation and multimodal, sure of critical normal structures compared with nongraphic
curative-intent treatment of dogs with AGASAC. 600,601,609,611,617 manual RT planning. 643 This has important implications for
Measurable response rates of 38% to 75% have been observed the interpretation of tumor control and toxicity profiles of older
in dogs with bulky disease treated with hypofractionated or frac- studies in which manual treatment planning was used. 643 It is
tionated protocols, suggesting radiosensitivity in the gross disease possible that contemporary and future studies that take advan-
setting 609,611,617,640 ; however, the role of RT for tumor control tage of sophisticated treatment planning systems and conformal
in the microscopic setting after surgical resection of primary or radiation delivery techniques may achieve different tumor con-
nodal AGASAC remains poorly defined. In a study of 113 variably trol rates and complication risks than those described in older
treated dogs, the use of adjuvant RT did not result in a significant reports. Radiation studies should also be evaluated in the con-
improvement in STs in 15 dogs. 600 This may have been due to low text of the regions that are irradiated, with reported radiation
statistical power, as the MST of these dogs was longest among the fields including the perianal region alone, perianal region and