ORAL MELANOMA

Gregory MacEwen, (608) 263-9815
               maceweng@svm.vetmed.wisc.edu

               Oral Melanoma Study at University
               of Wisconsin-Madison
                    A team of scientists is getting
               closer to releasing the results of their
               study on a treatment to boost a dog's
               immune system so it can fight a cancer
               of the mouth -- malignant oral
               melanoma, according to the Morris
               Animal Foundation.
                    "The study is providing
               encouraging results to date, with a
               relevant number of the participating
               dogs appearing to be in remission
               from cancer or having extended life
               spans resulting from the
               immunotherapy treatment," said Dr. E.
               Gregory MacEwen, lead investigator,
               University of Wisconsin-Madison
               School of Veterinary Medicine.
                    The final results are now being
               evaluated. "We look forward to
               releasing the findings of this study next
               year," said Dr. MacEwen.
                    Malignant oral melanoma
               aggressively spreads and establishes
               itself in other places in the dog's body,
               most commonly in the lungs and in the
               regional lymph nodes where the tumor
               grows. Despite surgery to remove
               these cancerous tumors, within two
               years as many as 90 percent of
               affected dogs will die from the spread
               of the cancer, reports the Foundation.
                    Dr. MacEwen and associates from
               the University of Wisconsin-Madison
               School of Veterinary Medicine, are
               collaborating with a team of
               veterinarians from five areas in the
               United States in the study. Funding for
               the study is provided by the Morris
               Animal Foundation.
                    According to Dr. MacEwen, oral
               melanoma is common in dogs with
               dark pigmentation inside their mouths,
               such as German shepherds and
               cocker spaniels.
                    Previous studies indicate that 10- to
               12-year-old males are at highest risk
               of getting malignant oral melanoma.
                    Dr. MacEwen study focuses on a
               new therapy following tumor removal to
               aid the dog's body in fighting off the
               spread of cancer. The treatment seeks
               to improve the immune system's ability
               to combat cancer that invades the
               body.
                    This immunotherapy, called
               "liposome encapsulated drug and
               growth factor," activates the cells of the
               immune system and causes activation
               in other disease fighting immune cells
               to ward off cancer.
                    Dogs with naturally occurring
               malignant melanoma are participating
               in this study with the consent and
               participation of their owners, says the
               Morris Animal Foundation.
                    These dogs are patients being
               treated at the veterinary hospitals at
               the University of California at Davis,
               University of Florida, Washington
               State University, Oakland Veterinary
               Referral Services in Michigan, and
               Veterinary Specialists in New York.

               MORE INFO:
               Morris Animal Foundation
               http://www.morrisanimalfoundation.org/

HEMANGIOSARCOMA

J Vet Intern Med 1993 Nov-Dec;7(6):370-6

Chemotherapy of canine hemangiosarcoma with doxorubicin and
cyclophosphamide.

Sorenmo KU, Jeglum KA, Helfand SC

Department of Clinical Studies, University of Pennsylvania, School of
Veterinary Medicine, Philadelphia.

Sixteen dogs with a histologic diagnosis of hemangiosarcoma were treated
with
surgery and
doxorubicin/cyclophosphamide. The patients' characteristics, ie, age, size,
and
breed, were similar to those of
previous studies. Historic controls for surgery alone were used to evaluate
efficacy of the chemotherapy. The
results show a trend of improved survival in dogs with localized disease
(Stage
I) receiving combination
therapy. The median survival was 250 days, with a mean of 403 days. The
survival times for dogs with stage I, II,
and III disease was also improved with combination therapy, when compared to
historical controls treated with
surgery alone. The overall median survival was 202 days with a mean of 285
days. Toxicities included mild to
moderate neutropenia (9 of 16) and clinical signs, such as lethargy,
anorexia,
vomiting, diarrhea, and fever (13
of 16). Three dogs had severe neutropenia requiring hospitalization and
supportive care. One dog died from
sepsis and related complications. Chemotherapy with doxorubicin and
cyclophosphamide appears to improve
survival with acceptable morbidity in patients with early stage disease.

PMID: 8114034, UI: 94157849
____________________________________________________________________________

HEMANGIOSARCOMA

Clin Cancer Res 1995 Oct;1(10):1165-70

Liposome-encapsulated muramyl tripeptide
phosphatidylethanolamine adjuvant immunotherapy for splenic
hemangiosarcoma in the dog: a randomized multi-institutional
clinical trial.

Vail DM, MacEwen EG, Kurzman ID, Dubielzig RR, Helfand SC, Kisseberth
WC, London CA,
Obradovich JE, Madewell BR, Rodriguez CO Jr, et al

Departments of Medical Sciences, School of Veterinary Medicine,
University of Wisconsin-Madison, Madison,
Wisconsin 53706, USA.

Canine splenic hemangiosarcoma (HSA) is a spontaneous tumor with high
metastatic potential. Despite
surgical excision, most dogs die within 2 months of diagnosis as a
result of widespread visceral metastasis.
This study was designed to determine the efficacy of
liposome-encapsulated muramyl tripeptide
phosphatidylethanolamine (L-MTP-PE) when used in combination with
splenectomy and systemic
chemotherapy for the treatment of HSA in the dog. Thirty-two dogs with
HSA and without gross evidence of
metastases were treated with splenectomy, stratified by clinical stage,
and randomized to receive
doxorubicin/cyclophosphamide chemotherapy and either L-MTP-PE
immunotherapy or lipid equivalent
(placebo liposomes). Dogs were subsequently followed to determine
disease-free survival and overall survival
times. The effects of L-MTP-PE on serum tumor necrosis factor-alpha and
interleukin 6 activity were assessed
on a small subset of dogs. Dogs receiving L-MTP-PE had significantly
prolonged disease-free survival (P =
0.037) and overall survival (P = 0.029) compared with dogs receiving
placebo. Dogs with clinical stage I
disease had significantly prolonged disease-free survival (P = 0. 026)
and overall survival (P = 0.017)
compared with dogs with clinical stage II disease. Dogs receiving
L-MTP-PE had significantly greater serum
tumor necrosis factor-alpha (P < 0.001) and interleukin 6 (P = 0.007)
activities compared with placebo-treated
dogs. L-MTP-PE has significant antimetastatic activity in highly
malignant, spontaneously occurring, splenic
HSA in the dog. Canine HSA may have potential as a large animal model
for additional investigation of
antimetastatic chemoimmunotherapy.

Publication Types:

    Clinical trial
    Multicenter study
    Randomized controlled trial

PMID: 9815908, UI: 99034926