Page 799 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 34 Miscellaneous Tumors 777

that although dogs mounted an HSA-specific immunity, there was parameters in normal dogs receiving oral YB 129,130 and a recent
no significant improvement in survival. 120 Dogs receiving adju- retrospective study evaluating a combination of YB and epsilon-
aminocaproic acid in dogs with presumed cardiac HSA suggested
vant AC chemotherapy combined with liposome-encapsulated
VetBooks.ir muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE), an no benefit in terms of time to recurrence of hemopericardium or
131
Polysaccharopeptide (PSP), the bioactive
immunomodulator derived from mycobacterial cell walls that
overall survival time.
increases monocyte tumoricidal activity, had a significantly better agent from the mushroom Coriolus versicolor, was recently evalu-
MST (9.1 months) than dogs receiving AC alone (5.7 months). 121 ated in a small pilot study in dogs with splenic HSA. A modest
Although approved for the treatment of osteosarcoma in humans numerical improvement in MST was noted in the high dose cohort
in the European Union, L-MTP-PE is not commercially avail- (n = 5) in comparison to historical controls receiving DOX-based
able in the United States and thus no further formal investigations therapy, although a true positive effect of PSP on time to metasta-
have been performed. sis and overall survival was not clearly evident based on statistical
analysis. 132
Radiation Therapy
Prognosis
RT is uncommonly used for HSA because of the predilection for
this tumor in visceral sites as well as the high metastatic rate. One Canine
study evaluating hypofractionated (palliative) RT for nonsplenic
HSA reported a high response rate, but no significant effect on The prognosis for canine HSA is highly dependent on tumor loca-
overall survival. 122 Hypofractionated RT has been evaluated for tion, stage of disease, and therapy pursued. A summary of the
dogs with cardiac HSA and in a pilot study appeared to reduce results of several reports on the treatment of splenic HSA is pre-
the frequency of cardiac tamponade, leading to an MST of 2.5 sented in Table 34.2. Overall, the prognosis for dogs with splenic
months. 123 HSA treated with surgery alone is extremely poor, with MSTs rang-
ing from 19 to 86 days, largely due to the high metastatic rate. 1–3,5
Targeted Therapies Therefore the generally accepted treatment approach for splenic
HSA includes DOX-based chemotherapy after surgery. Even
Given the marginal improvement in survival achieved with with the addition of chemotherapy, MSTs increase only to 5 to
conventional therapy for dogs with visceral HSA, the potential 7 months 99–103,107 and the 12-month survival percentage remains
application of more targeted therapies is certainly warranted. 10% or less. Stage plays a role in prognosis, where stage I (non-
Expression of receptor tyrosine kinase family members including ruptured, nonmetastatic) splenic HSA may have a more favorable
PDGF receptor (PDGFR), VEGF receptor (VEGFR), and stem outcome (MST 239–355 days) than stage II (ruptured) splenic
cell factor receptor (KIT), among others, has been documented HSA (MST 120–148 days) when postoperative chemotherapy is
in canine HSA. 29–31 Although in vitro assessments of targeted used. 107,121 One study incorporated a histologic grading scheme
small molecule inhibitors such as masitinib (inhibitor of PDGF into survival analysis and demonstrated that dogs with low-grade
and KIT), imatinib (inhibitor of KIT and PDGFR), and dasatinib tumors had a better prognosis than dogs with intermediate- or
99
(inhibitor of KIT, PDGFR, and SRC) have demonstrated growth high-grade tumors. Primary renal HSA may be associated with
inhibition and induction of apoptosis in canine HSA cell lines, a more favorable outcome than other visceral HSA, with an MST
the drug concentrations required for this effect in vivo may be dif- of 9 months in one small study. Conversely, retroperitoneal HSA
40
ficult to achieve without significant toxicity. 30,124 Toceranib phos- typically carries a poorer prognosis, with a reported MST of 37.5
41
phate (TOC, Palladia), which blocks signaling of KIT, PDGFR, days. For true cutaneous HSA, which includes superficial tumors
and VEGFR family members, has demonstrated in vivo activity involving the dermis only, surgical removal can often be curative
against multiple tumor types. 125 Although there is some interest in and MSTs of 780 to 987 days have been reported for dogs treated
the use of toceranib phosphate for HSA given the high expression with surgery alone. 14,38 In one study, dogs undergoing surgical
of VEGF and VEGFR, the administration of TOC in dogs with removal of dermal HSA were noted to have increased overall sur-
stage I or II HSA after splenectomy and DOX therapy resulted vival (MST 1570 days), particularly dogs with ventral tumor loca-
in no apparent improvement in median disease-free interval or tion (MST 1085 days), and those with evidence of solar-induced
MST. 126 eBAT, a bispecific epidermal growth factor (EGF)-uro- changes on histopathology (MST 1549 days). Conversely, dogs
14
kinase angiotoxin, was evaluated in a small group of dogs before whose cutaneous tumors displayed subcutaneous invasion had a
standard DOX chemotherapy, leading to an MST of 8.5 months higher chance of developing metastasis (relative risk 2.04) and a
and a 6-month survival rate of 70.6%, both of which were signifi- subsequently poorer longterm survival (MST 539 days). HSAs
14
cantly improved compared with a historical control group receiv- originating in the subcutaneous and intramuscular tissues are typi-
ing DOX only. 127 cally more aggressive than dermal HSA, with higher metastatic
rates and shorter MSTs. 6,38,66,68 Therefore adjuvant chemotherapy
Alternative Therapies is typically part of recommended therapy for dogs with subcutane-
ous and intramuscular HSA. 66,68 Two studies reported divergent
Yunnan Baiyao (YB), a Chinese herbal medicine that has long results, where one study reported an MST of more than 3 years for
been used for its antiinflammatory, hemostatic, pro-wound heal- dogs receiving adjuvant DOX after surgical removal of subcutane-
ing, and analgesic properties in people, has also been anecdotally ous HSA, and 9 months for dogs undergoing the same treatment
66
used to control bleeding in dogs with both nonmalignant and for intramuscular HSA. The other study reported an overall
malignant conditions, including HSA. In a preliminary in vitro MST of 8 months for dogs with nonmetastatic subcutaneous or
68
study, YB led to dose- and time-dependent cell death via caspase- intramuscular HSA treated similarly. For dogs with apparently
mediated apoptosis in three canine HSA cell lines 128 ; however, two inoperable subcutaneous or intramuscular tumors, DOX-based
laboratory studies demonstrated no modulation of coagulation chemotherapy may offer some palliation and, in one study, some