Treatment Protocols to Prolong a Dog’s Lifespan with HemangiosarcomaCaryn FrazierAnimal Science Seminar

What’s the Issue?

•About 50% of pet deaths are due to cancer

•Leading cause of death in older dogs•A concern for pet owners

Definitions

•Anthracycline: antibiotic that comes from Streptomyces bacteria▫Damage DNA in cancer cells▫Causing cell death

•Metastasis: spread of cancer from one part of body to another

•Endothelial Cell: cells that lie within the endothelium of blood vessels

What is Hemangiosarcoma (HSA)?

• An aggressive form of cancer that effects endothelial cells ▫Approximately 7% of canine cancer is due to HSA

• Can happen in any tissue or organ, but primary tumors are commonly seen in:

Spleen, liver, right atrium, kidney, bladder, skin, lungs, and muscle

• Happens in any breed of dog, but commonly seen in: Golden Retrievers, German Shepherds, Labrador

Retrievers, Schnauzers, and Poodles

• Early clinical signs:▫Weakness, depression, pale mucous membranes,

increased pulse and respiration, splenic enlargement

• Most dogs show no clinical signs, but late-stage disease▫Collapse due to anaphylactic shock from the organ or

tissue nodules bursting Leads to bleeding out into abdominal cavity

• Previous research by Brown et al. (1985) resulted in a median survival of 86 days for surgery only

HSA in the liver

Objective

•To examine various chemotherapy protocols in increasing a dog’s lifespan with Hemangiosarcoma.

Kim et al. (2007)

•Objective: To determine the efficacy of Epirubicin after splenectomy compared to no therapy after splenectomy in HSA dogs.

Key Terms

•Epirubicin=anthracycline, stereoisomer of Doxorubicin (DOX), antineoplastic effect

•Survival Time: time from surgery until death

Kim et al.(2007)

•59 dogs ▫18 dogs splenectomy and Epirubicin

Received at 30 mg/m2, every 3 weeks 4-6 cycles

▫41 dogs splenectomy alone•First dose of Epirubicin median of 21

days, range 9-139 days

Survival Times Between the Two Treatments

Figure 1: Ticked lines resemble dogs censored from study. Chemotherapy group median survival time 144 days (range 74-2,717 days). Nonchemotherapy group median survival time 87 days (range 14-790 days). Comparing the two treatments, resulted in a P Value=0.04, statistically significant difference.

=Surgery Alone

=Surgery & Epirubicin

Adapted from Kim et al., 2007.

Conclusion

•Epirubicin increases the survival time compared to surgery alone

Teske et al. (2011)

•Objective: Compare the use of Pegylated Liposomal Encapsulated Doxorubicin (PL-DOX) compared with free Doxorubicin (DOX) as a therapy in dogs with splenic HSA following splenectomy.

Teske et al. (2011)

•DOX: Anthracycline, antineoplastic drug

•PL-DOX: phospholipid layer (liposome) enclosure of the drug to deliver to site of action▫Prevents from immune destruction

•Disease Free Period: time from splenectomy to evidence of metastasis

Teske et al. (2011) •Randomized•36 dogs•All had splenectomy prior to treatment

▫34 dogs used in study 17 dogs in each treatment group

▫PL-DOX Given at 20 mg/m2, IV

▫Free DOX Given at 30 mg/m2, IV

▫Treatments were given every 3 weeks, for 6 cycles

Disease Free Period of PL-DOX vs Free DOX

Figure 2: Time from splenectomy to evidence of metastasis in dogs treated with PL-DOX and free DOX. Median disease free period for PL-DOX dogs was 153 days. Median disease free period for free DOX dogs was 172 days. Results not significant (P>0.05).

Adapted from Teske et al.,2011.

Conclusion

•Median Survival Time▫PL-DOX=166 days (range 144-188)▫Free DOX=172 days (range 130-214)▫Results were not significant

•PL-DOX didn’t appear to have a greater effect on survival time compared to free DOX

Brown and Reetz (2012)

•Objective: Determine the effects of dosage on efficacy of mushroom extract (I’m Yunity) on dogs with HSA.

Brown and Reetz (2012)•I’m Yunity: dietary supplement of turkey

tail mushroom

•Polysaccharopeptide (PSP): likely bioactive agent in the mushroom▫In vitro antitumor activities ▫Inhibits growth of induced tumors in rodent

models

Brown and Reetz (2012)

•Randomized, double-blind study▫5 dogs per treatment (15 total)

25, 50, and 100 mg/kg/day of I’m Yunity All given in capsule form

▫All 15 dogs had splenectomy

Days to progression of abdominal metastasis

Figure 3: 15 dogs diagnosed with splenic HSA, randomized to one of three doses of I’m Yunity (5 in each group). *Denotes a statistical difference (P=0.046). The 25mg/kg/day had a median time of metastasis of 30 days (range 16-126). The 50 mg/kg/day had a median time of metastasis of 35 days (range 23-331). The 100 mg/kg/day had a median time of metastasis of 112 days (range 30-308).

Adapted from Brown and Reetz, 2012.

Survival Curve of the Three Treatment Groups

Figure 4: Survival curve between all three treatment groups. The 50 mg/kg/day group had a median survival time of 187 days and the 100mg/kg/day had a median survival time of 199 days. No significant difference was seen between the 3 treatment groups.

Pro

port

ion

of

Dog

s

Adapted from Brown and Reetz, 2012.

Conclusion

•The I’m Yunity may help with slowing down metastasis▫Median time to progression 30, 35, and 112

days Indicated in Figure 3

▫Further studies need to be conducted Larger group of dogs

•Didn’t appear to help survival time of dog’s (Figure 4)

Objective

•To examine various chemotherapy protocols in increasing a dog’s lifespan with Hemangiosarcoma.

Final Conclusion

•Surgery alone to remove primary tumor didn’t seem to be as effective

•Following up with Chemotherapy is advisable, but open to question

•Still need larger samples in all studies▫Controls are ethically difficult to use▫Depends on stage of disease

Implications

•Epirubicin can be used in treating HSA

•I’m Yunity may be useful in slowing progression of HSA▫If owner chooses to forego Chemotherapy

treatment

•DOX can be used following surgery

ReferencesBrown, D.C., and J. Reetz. 2012. Single agent polysaccharopeptide delays metastases and improves survival in naturally occurring hemangiosarcoma. Evid. Based Complement. Alternat. Med. doi:10.1155/2012/384301.

Brown, N.O., A.K. Patnaik, and E.G. Macewen. 1985. Canine hemangiosarcoma: retrospective analysis of 104 cases. J. Amer. Vet. Med. Assn. 186:56-58.

Kim, S.E., J.M. Liptak, T.T. Gall, G.J. Monteith, and J.P. Woods. 2007. Epirubicin in the adjuvant treatment of splenic Hemangiosarcoma in dogs: 59 cases (1997-2004). J. Amer. Vet. Med. Assn. 231:1550-1557

Teske, E., G.R. Rutteman, J. Kiprenstein, and J. Hirschberger. 2011. A randomized controlled study into the efficacy and toxicity of pegylated liposome encapsulated doxorubicin as anadjuvant therapy in dogs with splenic Hemangiosarcoma. Vet. Comp. Oncol. 9:283-289.

Questions??