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Palliative Care Dr Veronika Langova

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Palliative Care Dr Veronika Langova Palliative care Veronika Langova MVDr, MANZCVS (Med) FANZCVS (Onc) • Pet palliative care focuses on alleviating patient discomfort and controlling clinical signs while addressing the client's emotional needs. • Fundamental concerns are pain management, hygiene, nutrition, mobility and safety in the home. • The next tier of care focuses on the pet's mental state and engagement with human family Palliative care members as well as interactions with other household pets. • Cancer is the Leading Cause of Pet Animal Death • 45% of 10 to 16 year old dogs • 23% overall American Journal of Veterinary Research 1982 Increasing Prevalence Due to Increasing Age • Preventive medicine better management of diseases • Vaccinations • Nutrition • Human-animal bond Psychological Implication to the Owner • 1 in 4 get cancer • Experience of cancer • Negative attitude detrimental Cancer treatment • 1/3 we can cure • 1/3 we can manage for prolonged period of time ‘remission’ • 1/3 we palliate • Using chemotherapy • Radiation • Pain management • Nutritional support Palliative care • USING CHEMOTHERAPY Ben Ten • 10 yo MN LabxKelpie • Owner noticed snoring and occasional sneezing 6 months ago • Recently developed epistaxis Ben Ten CT scan Histopathology immunohistochemistry Ben Ten CD3 (Tcell) CD79 (Bcell) Spike • 14 yo MN Cattle dog • Presented with large mass on the left mandible, left submandibular lymph node enlargement • Histopathology: T cell lymphoma ROXY Roxy • cytology • What about muzzle MCT? • Geiger et al JVIM 2003 • 24 dogs with muzzle MCT ROXY • 2 Grade I, 15 Grade II, 7 Grade III • Median survival 30 months • Grade was prognostic for local control of disease and survival Ellis Imaging • Histopathology soft tissue sarcoma METRONOMIC CHEMOTHERAPY • Administration of large boluses of chemotherapy with a period of ‘recovery’ between doses describes traditional maximum tolerable dose (MTD) chemotherapy Researchgate 17 METRONOMIC CHEMOTHERAPY • Low dose daily chemotherapy administration without the need for a recovery period describes metronomic chemotherapy Researchgate 18 METRONOMIC CHEMOTHERAPY Mechanisms of action of metronomic chemotherapy: 1. Effects on neovascularisation 2. Effects on the immune system 3. Effects on cancer cells and cancer stem cells 4. Induction of tumour dormancy 19 METRONOMIC CHEMOTHERAPY • Angiogenesis is the formation of new blood vessels and is a Hallmark of Cancer • Numerous pro-angiogenic factors involved • Inhibition of angiogenesis can prevent tumour growth and potentially cause tumour regression 20 METRONOMIC CHEMOTHERAPY • Angiogenesis inhibitors are an emerging field in cancer therapy • Metronomic chemotherapy utilising anti-neoplastic drugs • Monoclonal antibodies • Tyrosine kinase inhibitors • Thalidomide 21 METRONOMIC CHEMOTHERAPY • Effects on the immune system – “immune escape’ is now considered a Hallmark of Cancer • T-regulatory cells (Tregs) are important immunosuppressive cells that can prevent immune detection of tumour cells by the rest of the immune system • Increased numbers of Tregs have been detected in tumours and circulating in cancer patients 22 METRONOMIC CHEMOTHERAPY • Reductions in circulating Treg numbers have been shown to occur with metronomic chemotherapy treatment • Most frequently used drug is Cyclophosphamide • Alkylating agent used in both MTD and metronomic protocols 23 METRONOMIC CHEMOTHERAPY • Cancer stem cells have many unique properties • Metronomic chemotherapy can disrupt the CSC niche through anti-angiogenic effects • Direct cytotoxicity (minor) IntechOpen 24 First work showing evidence for metronomic chemotherapy published in 2002 for human breast cancer Metronomic • First published studies in canine cancer chemotherapy (haemangiosarcoma and STS) published 2007 “The use of low-dose metronomic chemotherapy in dogs – an insight into a modern cancer field” Gaspar et al, VCO2017 Ellis 7 months on metronomic chemotherapy before having signs of PD effecting her quality of life • Using chemotherapy • Radiation • Pain management • Nutritional support Palliative care • Radiation • Cure or shrink early stage cancer • Stop cancer from reoccurring somewhere else ( lymph nodes, other organs such as lung brain) What are the • Treat symptoms caused by advanced cancer goals of RT? (pain, trouble swallowing or breathing, bowel blockage) • Treat recurrent cancer • Internal Radiation Therapy (Brachytherapy) • Placement of a radioactive implant inside the body in or near the tumor. • Nasal tumors cutaneous SCC Types of RT • Systemic Radiation Therapy • Radioactive are used to treat certain types of cancer systemically. • radioactive iodine, strontium, samarium, and radium. • Definitive therapy • Objective is long term local control • Higher total doses of radiation given over multiple (daily) fractions in smaller individual doses • More acute side effects while sparing late responding tissues Intention of • Goal is to limit late toxicity to critical structures • Radiation E.g. 2.5 Gy x 20 fractions = 50 Gy total • Mast cell tumors Therapy • Soft tissue sarcomas • Brain tumors • Spinal tumors • Thyroid tumors • Variety of carcinomas • Palliative therapy • Objective is to alleviate clinical signs associated with the tumor • Improve quality of life rather than long-term tumor control Intention of • Less intense treatment schedule – once weekly or daily for low total dose Radiation • Less acute side effects but higher risk of late effects Therapy • E.g. 8 Gy x 4 fractions = 32 Gy total • Osteosarcoma • Metastatic ASAC • Thyroid tumors • melanoma Mefodiy • 6 yo Irish wolfhound cross male • Hx of lameness for 3 weeks • Swelling of the carpus Mefodiy • Examination • Fairly unremarkable • Firm immobile mass left carpus moderate soft tissue swelling • Diagnostics • CBC and Biochemistry – unremarkable- PF?? • Thoracic and abdominal CT Mefodiy Stereotactic radiosurgery for Tx of osteosarcomas in distal limb Farese JAVMA2004 11 dogs dose 20-30 Gy MST 363 days 4/11 pathological fracture 5.8 months after SRS Outcome and complications in dogs with appendicular OSA Tx with SRT and concurrent stabilization Boston VS2017 18 dogs with SRT (1x30Gy or 3x12 Gy) had their tumor surgically stabilised complications in 16/17, 15 being major infections and fractures most common 9 dogs amputated at 152 days MST for all dogs 345 days Mefodiy • Treatment • Pamidronate 1 mg/kg IV once a month • Stereotactic radiation 3x • Carboplatin 300 mg/m2 IV Q 3weeks • Using chemotherapy • Radiation • Pain management • Nutritional support Palliative care • Pain management Multimodal analgesia • Aims to block the pain pathways at multiple sites, using agents with different modes of action • More effective pain control ALPHA2 • Reduced prevalence of side effects AGONISTS OPIOIDS OPIOIDS KETAMINE ALPHA2 LOCAL ANAESTHETICS ALPHA 2 NSAIDS OPIOIDS • NSAIDs • Paracetamol • Opioids • Alpha 2 agonists • +/- Ketamine • Loco-regional block Severe acute pain Paracetamol • Weak inhibitor of PGs synthesis (weak anti-inflammatory properties) • Analgesic and anti-pyretic effects • May act on cannabinoid receptors • Activates TRPV1 rec – responsible for central and peripheral pain transmission • Activates serotoninergic pathway • Inhibits nitric coxide and tumour necrosis factor ⍺ • Contraindicated in cats • Minimal side effects • No good evidence of effective dose, duration or analgesic effects Opioids • Oral, injectable, transdermal, transmucosal • Drugs availability • Methadone, morphine, fentanyl - full µ agonists • Buprenorphine - partial µ agonist • Butorphanol - µ antagonist and κ agonist • Methadone vs fentanyl • Duration of action (fentanyl < methadone) • Potency (fentanyl > methadone) • Methadone vs morphine • Decreased incidence of vomiting • Decreased incidence of histamine release • Methadone 0.3 mg/kg IV or IM • NSAIDs • Paracetamol • Ketamine • Gabapentin • Amantadine • Codeine versus Tramadol Chronic pain Gabapentin • Neuronal Calcium channel inhibitor • Decrease release of excitatory neurotransmitters • 5-10 (10-20) mg/kg PO BID or TID • Neuropathic pain • Safely combined with other drugs • Main adverse effects are sedation and ataxia • Tend to improve over time Amantadine • Dopamine agonist and NMDA receptor antagonist • Originally used as an antiviral agent • Chronic pain in particular with central sensitization • 3-5 mg/kg SID (may go up to BID) – may take up to 2 weeks to have an effect • Rare side effects • CNS stimulation at high doses (Avoid co-administration with serotonin reuptake inhibitors) • Vomiting and diarrhea Tramadol Tramadol •Noradrenaline reuptake inhibition •Serotonin reuptake inhibition •µ opioid receptor agonism (low affinity) M1 metabolite (little production in dogs) •µ opioid receptor agonism Variability in efficacy (no good evidence of effect) 2-5 mg/kg PO BID Side effects •Sedation •Vomiting ad diarrhea • µ opioid agonist • In dogs: 4% oral bioavailability • negligent amount of morphine metabolite • Codeine 6 glucuronide may provide some analgesic effects • 1-2 mg/kg PO q 8-12 h Codeine Oral/Skull SCC • Monthly bisphosphonates infusion 1 mg/kg IV over 2 hours • Oral toceranib as metronomic chemotherapy • Oral NSAIDs Oral tablets (aledronate), IV infusions (pamidronate, zoledronate) Used in humans to treat bone loss and osteoporosis Adjunctive • Inhibit ingestion of bone by osteoclasts therapies - Bisphosphonates Useful for bone metastasis – pain relief, strengthen bone • Not actual chemotherapy Idiopathic hypercalcaemia in cats Certain tumour types have been shown to over-express COX receptors and
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