Systemic Cancer Therapy Flashcards
When is chemotherapy considered a preferred treatment? What cells does it target?
systemic disease —> metastasis
rapidly dividing cells - GI crypt, bone marrow, hair
What are the mechanisms of action of akylating agents, mitotic spindle inhibitors, and antitumor antibiotics? What are some examples of each?
adds an alkyl group to DNA, causing strand breaks —> cyclophosphamide, chlorambucil
attach to microtubules during mitosis —> vincristine, vinblastine
inhibit topoisomerase II, intercalate DNA, and cause free radical formation —> doxorubicin, mitoxantrone
What are the mechanisms of action of platinum drugs, antimetabolites/nucleotide analogs, and chemotherapeutic enzymes? What are examples of each?
binds platinum to DNA —> carboplatin
incorporates altered nucleotides into DNA during S phase —> Tanovea
depletes body of asparagine necessary for cell division —> L-asparaginase
How is the GI system affected by chemotherapy? What signs does this result in?
damages the crypt cells, resulting in shortened crypts, blunting of villi, and reduced absorption
decreased appetite, vomiting, and diarrhea 2-3 days post-treatment (time it takes for the damaged crypt cells to migrate up)
What treatments are recommended to relieve GI signs?
usually mild and self-limiting, hospitalization not usually necessary
- decreased appetite = Cerenia, Mirtazapine, Entyce
- vomiting = Cerenia, Ondansetron
- diarrhea = Metronidazole, fluids
How does chemotherapy affect the bone marrow? What does this result in? What does not occur?
damages bone marrow precursors
neutropenia and thrombocytopenia with the nadir at around 7-10 days (time it takes for circulating cells to die) —> rebound leukocytosis seen after!
acute anemia —> RBCs have a longer lifespan, allowing them to circulate longer
Is treatment common necessary for neutropenia and thrombocytopenia resulting from chemotherapy treatment?
only if a fever develops
- low grade (103-104.5) = antibiotics (TMP-S, marbofloxacin, clavamox) +/- fluids
- high grade (>104.5) = hospitalization, IV antibiotics and fluids, Neupogen (exogenous GCSF to stimulate neutrophil growth)
Why is Neupogen not commonly given to patients with neutropenia caused by chemotherapy?
- expensive
- rebound neutrophilia typically results after nadir
- most hospitals don’t carry a stock and by the time a delivery comes in, rebound neutrophilia would likely occur
What side effect can be seen around the catheter site with chemotherapy treatments?
extravasation injury —> severe damage to perivascular tissues if drug leaks outside of the vein during administration (not all drugs!)
- can be severe enough to require amputation
What treatment is recommended for extravasation injuries? What is a drug-specific antidote available?
- pull back on plunger to clear the line of the drug
- place a warm compress for mitotic spindle inhibitors or a cold compress for others to keep the drug from spreading
Dexrazoxane for Doxorubicin
What breeds most commonly develop hair loss in response to chemotherapy? What can happen in cats?
breeds with continuous (anagen phase) hair growth —> Poodles, Bichon Frise, Schnauzers, OESD (clipped hair can regrow slowly)
lose whiskers and guard hairs, resulting in a “chemo coat” of softer hair
What specific side effect is seen with Doxorubicin? What should be done in at-risk patients?
cardiotoxicity due to myocardial damage from free radicals, resulting in irreversible DCM, decreased fractional shortening, and (supra)ventricular arrhythmias (dose-dependent)
pre-treatment echo, especially in Boxers and Dobermans
What specific side effect is seen with Cyclophosphamide? What signs does this result in?
sterile hemorrhagic cystitis caused by the metabolite, acrolein (dogs!)
hematuria, pollakiuria, dysuria a few days after treatment
How can sterile hemorrhagic cystitis be avoided with Cyclophosphamide treatment? How is it treated?
give Furosemide to dilute acrolein
- get a urine culture and treat infection if present
- NSAIDs, prednisone
- oxybutynin - relax detrusor
- DMSO
(can take months to heal or be permanent)
What specific side effect is seen with Vincristine treatment? What signs are seen?
paralytic ileus due to peripheral neuropathy in dogs and cats
cessation of peristalsis results in restlessness, pacing, painful abdomen, anorexia, vomiting, and tenesmus within 7-10 days post-treatment
How is paralytic ileus due to Vincristine treatment treated?
metclopramide (prokinetic) + supportive care
What specific side effect is seen with CCNU (Lomustine) treatment? What signs are seen?
hepatotoxicity in dogs —> delayed chronic hepatopathy
usually no clinical signs, but can result in elevated ALP and ALT
- ALT more concerning
How can hepatotoxicity as a result of CCNU treatment be prevented?
- Denamarine pre-treatment
- decrease dose, increase time between treatments
- discontinue if ALT is elevated
What are 2 specific chemotherapies not recommended for cats? Why?
- Cisplatin - pulmonary edema (cisplat splats cats!)
- 5-Fluoruracil - neurotoxicity
FATAL
What is metronomic chemotherapy? When is it typically used?
daily low-dose oral chemotherapy administration to attain anti-angiogenic effects, rather than cytotoxicity —> blocks receptors responsible for formation of new blood vessels, like COX-2 and VEGF, and damages endothelial cells
- HSA
- osteosarcoma
- soft tissue sarcoma
- SCC
- TCC
What are the 3 most common chemotherapies used as metronomic therapy? What are they commonly combined with?
- cyclophosphamide (Cytoxan)
- chlorambucil (Leukeran)
- CCNU (Lomustine)
NSAIDs for further anti-angiogenic properties - Piroxicam, Deramaxx, etc.
What is the mechanism of action of tyrosine kinase inhibitors? What 2 are used in veterinary medicine?
bind to various tyrosine kinase receptors on the surface of cancer cells to induce anti-angiogenic effects
- Palladia (toceranib)
- Masivet (masitinib, not available in US)
What method of administration is used for Palladia? What is it used to treat? What side effects are commonly seen?
oral —> Mon/Wed/Fri
originally curated for MCT treatment, but is now used for carcinomas > sarcomas
- GI - decreased appetite, vomiting, GI ulceration, diarrhea
- BW - neutropenia, thrombocytopenia, hypoalbuminemia
- UA - proteinuria, azotemia
