Page 1406 - Clinical Small Animal Internal Medicine

1344 Section 11 Oncologic Disease

Angiogenesis inhibitors are an attractive antineoplastic may also eventually be produced, making the use of esca­
VetBooks.ir treatment as they are not limited to cytotoxic therapy lating doses necessary.
Matrix metalloproteinases (MMPs) are another poten­
and may be more acceptable and tolerable by both
the owner and the patient. Further, they do not induce
nents of the extracellular matrix, and play an important
multidrug resistance as they do not target tumor cells tial target for therapy. These enzymes degrade compo­
directly. role in wound healing and tissue remodeling. In the can­
cer patient, MMPs are involved in tumor invasion, prolif­
Metronomic Chemotherapy eration, and fostering a local environment to enhance
Metronomic or continuous low‐dose oral chemotherapy tumor growth. Minocycline is a synthetic agent that
has been demonstrated to have antiangiogenic and inhibits MMPs. However, its use has not been shown to
immune‐modulating effects. Its use has been shown to significantly prolong survival in dogs with HSA when
improve survival in dogs undergoing splenectomy. combined with a doxorubicin‐containing protocol.
Cyclophosphamide, the most commonly prescribed, also
suppresses T‐regulatory cells, thereby improving host Complementary Treatment
antineoplastic immune function. In one study, cyclo­
2
phosphamide (12.5–25 mg/m PO) and etoposide Nutraceuticals or homeopathic remedies have been
2
(50 mg/m PO) were administered daily on alternating explored as adjuncts to standard therapy for hemangio­
three‐week cycles with piroxicam (0.3 mg/kg/day PO). sarcoma in an effort to improve quality of life. Yun‐Zhi
Results revealed a median survival of 178 days, which PSP is the active ingredient in I’m‐Yunity (an extract of
was significantly better than historical controls undergo­ Coriolus versicolor mushroom). The median time to
ing surgery alone. Although low doses of chemotherapy develop metastasis or progression of metastasis was
are used, owner compliance and care are required to delayed in dogs receiving 100 mg/kg/day. Yunnan Baiyao
minimize risks for sterile hemorrhagic cystitis. is a neutraceutical/homeopathic Chinese powder that
To date, very few metronomic protocols have been anecdotally has been shown to promote coagulation, and
evaluated in patients with hemangiosarcoma. Further help prevent intraabdominal and myocardial hemorrhage.
studies need to be done to determine efficacious drugs, The definitive benefit of its use in dogs with hemangiosar­
dosages, and timing. coma has yet to be determined.

Tyrosine Kinase Inhibitors Prognosis
Palladia™ (toceranib phosphate) is a receptor tyrosine
kinase inhibitor that affects the activities of multiple
receptors, including VEGF and PDGF‐alpha. Similar to Visceral and Myocardial Forms
metronomic chemotherapy, it also has immunomodula­ The long‐term prognosis is grave for dogs with the vis­
tory effects against myeloid‐derived suppressor cells. ceral form of hemangiosarcoma. The median survival
Masitinib mesylate (Masivet®), another receptor tyrosine time (MST) with surgery alone is approximately 72 days.
kinase inhibitor approved for use in dogs in Europe, was With adjunctive chemotherapy, the median survival time
shown to decrease T‐regulatory lymphocytes in the is 6 months (one­year survival 6%). Stage has been shown
bloodstream of dogs and was well tolerated when com­ to be prognostic. Dogs with a stage III presentation have
bined with a metronomic dosage of cyclophosphamide. an anticipated MST of three months in spite of standard
However, neither Palladia nor Masivet has been shown therapy. Death is typically due to resistant metastatic
to lead to survival benefits for HSA. Imatinib mesylate disease or hemorrhage.
(Gleevec®), a human receptor tyrosine kinase inhibitor, The prognosis for dogs with myocardial HSA is like­
has been shown to induce apoptosis in hemangiosar­ wise grave. Although survival may be similar to those
coma cell lines with a dose‐dependent killing effect with the visceral form, a poorer outcome is more typical
in vitro. It is associated with hepatotoxicity in the dog (MST 4 months) as many do not undergo cytoreductive
and for most, is cost‐prohibitive. surgery. In one study, the MST for dogs that had pericar­
dectomy alone was one month.
Other Agents Both renal and lingual forms are exceptions. With
Interferons are cytokines that have been used for antian­ treatment, renal hemangiosarcoma has a MST of nine
giogenic therapy in humans; interferon‐alpha 2a inhibits months, with an approximately 30% one‐year survival.
angiogenesis by suppressing bFGF and VEGF produc­ Dogs with lingual hemangiosarcoma (grade I and II)
tion. Daily injections are required, making it less practi­ have an expected MST of 553 days. Local recurrence
cal for the veterinary patient. Neutralizing antibodies following therapy for the lingual form is common.