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152 Hemangiosarcoma 1343

Complete surgical excision of dermal hemangiosar­ erythrodysesthesia (PPES), a painful desquamation
VetBooks.ir coma is strongly recommended. If the mass is small dermatitis. Adjunctive therapy with pyridoxine may
minimize symptoms and lessen risk.
and no evidence of subcutaneous invasion is found,
Other notable toxicities of anthracyclines include
adjunctive chemotherapy may not be warranted as the
risk of metastasis for this form is low. anaphylactic type reactions during infusion and tis­
Unlike dermal tumors, where surgical excision alone sue necrosis if extravasated. Proper administration
may be adequate, hypodermal and intramuscular tumors requires accurate intravenous catheter placement,
require multimodal therapy. HSA in this location is patient sedation when appropriate, and avoiding
associated with a high local recurrence and metastatic bolus administration.
rate. Therefore, wide surgical excision (3 cm minimum In the cat, adjunctive chemotherapy with a doxoru­
margin) +/‐ adjunctive radiotherapy is recommended. bicin‐based protocol is recommended following surgical
To address the risk of metastasis, systemic chemother­ excision for all forms of HSA except small dermal lesions.
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apy (doxorubicin based) is always recommended. Single‐agent doxorubicin dosed at 25 mg/m every three
In cats, complete histopathologic excision with wide weeks, or a combination protocol with cyclophosphamide
surgical margins is likewise recommended for all dermal and vincristine, should be considered.
forms of hemangiosarcoma. As in dogs, subcutaneous
and other nondermal hemangiosarcoma forms have a Immunotherapy
higher risk of metastasis. Hence adjunctive chemother­
apy should be considered. Immunotherapy modifies a biologic response by enhanc­
ing a preexisting immune response, inducing an immune
response or suppressing an immune response. When
Doxorubicin‐Based Chemotherapy
given in conjunction with chemotherapy, immunomod­
Doxorubicin is the most active chemotherapeutic for ulatory agents may enhance efficacy and improve
hemangiosarcoma. It can be used alone or as part of a prognosis. One such immunomodulatory agent is mura­
multiple agent protocol (see Table 152.2). Regardless of myl tripeptide‐phosphatidylethanolamine (L‐MTP‐PE),
which is utilized, chemotherapy is regarded as well a lipophilic derivative of muramyl dipeptide (MDP), a
tolerated by most animals. Gastrointestinal toxicity molecule resembling the cell wall of bacteria. L‐MTP‐
(vomiting, diarrhea, anorexia) is often self‐limiting and is PE stimulates cells of macrophage lineage to become
seen in up to 20% of patients, but requires hospitaliza­ tumoricidal. When a doxorubicin‐based protocol was
tion far less often. Like most chemotherapeutics, the used in conjunction with L‐MTP‐PE (given twice weekly
most common hematologic side‐effects are neutrope­ for eight weeks), the median survival time was signifi­
nia and thrombocytopenia, and, less likely, anemia. cantly improved (277 days versus 143 days with chemo­
Doxorubicin‐based protocols that incorporate dacar­ therapy alone). L‐MTP‐PE is not presently available in
bazine result in a response rate of 47% but have more the United States.
significant hematologic and gastrointestinal side‐effects.
Oral temozolomide in place of dacarbazine has recently Antiangiogenic Therapy
been evaluated. The response rate was found to be
similar but with less hematologic toxicity. Angiogenesis is a normal process involved in fetal devel­
Doxorubicin, like all anthracyclines, is cardiotoxic. An opment, wound healing, and the female reproductive
irreversible, dilated type cardiomyopathy can occur at cycle. In health, it is controlled by inhibitory regulators.
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cumulative doses at or above 180–240 mg/m . A more In the cancer patient, this process becomes abnormally
cardioprotective anthracycline is epirubicin. Adverse activated and unregulated and is involved in tumor
cardiac effects can be seen with its use but at doses growth and metastasis.
more than double that of doxorubicin. In one study, it Newer cancer treatment strategies focus on the
was shown to be equally effective as doxorubicin, but inhibition of angiogenesis. Growth factors monitor and
more gastrointestinal side‐effects (vomiting, diarrhea) activate endothelial cell growth and development. As
occurred. Other formulations of doxorubicin such as examples, VEGF and bFGF act directly on endothelial
pegylated, liposome‐encapsulated (PL‐DOX) are availa­ cells; Transforming growth factor (TGF) and platelet‐
ble. Encapsulation into liposomes leads to decreased derived growth factor (PDGF) attract and activate
cardiotoxicity and decreased drug uptake by phagocytes, inflammatory cells and connective tissue, which thereby
thereby prolonging exposure to the drug. Comparison promotes angiogenesis. Antiangiogenic agents are
of response and survival time between pegylated directed towards inhibition of one or more growth
and nonpegylated forms has revealed no differences. factors or their receptors, thereby preventing further
Of unique concern, PL‐DOX may induce palmar‐plantar angiogenesis, growth and metastasis of a tumor.