Theraptutic Oncology Flashcards
What are the main goals of chemotherapy in veterinary medicine?
Enhance or at least maintain quality of life
Stabilize, diminish, or eliminate neoplastic process
What type of cells does chemotherapy target?
Rapidly dividing cells
—> tumor cells
—> gut, bone marrow, and hair follicles
What is fractionated dosing?
Allows recovery of normal tissue between treatment intervals
-cycle =treatment and recovery period
What does it mean to used chemotherapy as an adjunct therapy?
Add on to a local therapy (eg surgery)
What does it mean to use chemotherapy as a neoadjuvant?
Prior to definitive treatment (surgery) in attempt to shrink tumor
What does in mean to use chemotherapy for induction/maintenance?
Sole treatment for measurable disease (Eg LSA)
When would we use chemo as a palliative treatment?
Improve quality of life by helping alleviate signs
What information do you require before administration of chemotherapy?
Accurate diagnosis —> tumor type that is known to respond to anti neoplastic agents
Appropriate staging
Initial stabilization performed -> correct dehydration, electrolyte imbalance, renal function, hepatic function, and anemia
Client communication
Alternative treatment options explored and discussed with the owner
T/F: chemotherapy is dosed based on efficacy
False
Dosed based on toxicity — to prevent treatment failure drugs are administered at highest possible doses
How should chemotherapy doses be calculated??
With body surface area —> more accurate predictor of physiological function
Small patients may be overdosed on this basis —> use body weight
In what dog breeds should you decreased your chemotherapy doses?
White feet dont treat!
Australian shepherd
Collies
Long-haired whippet
ABCB-1 gene codes for the production of p-glycoproteins pumps, which act to remove drugs from individual cells —> mutated in these does
What chemotherapy drugs have increased risk in collies, and by how much should you decrease the dose?
Vincristine
Vinblastine
Paclitaxel
Boxorubicin
30-40% of the required dose
What are the common adverse effects of chemotherapy?
Bone marrow suppression: myelosuppression (neutropenia/thrombocytopenia)
Alopecia: non shedding breeds only
Gastrointestinal: crypt cells are destroyed—> vomiting and diarrhea
What percentages of patients receiving chemotherapy have none to minimal side effects?
80-85%
What percentages of patients receiving chemotherapy required hospitalization due to significant adverse effects?
3-5%
What monitoring of the patient will you do prior to administering their dose of chemotherapy?
CBC
In order to give chemo , Neutrophils > 3000/ul and platelets > 100,000/ul (if to low no treatment and recheck in 3-7days)
After 1st chem: CBC at NADIR
- > shows expected low of BM insult
- > Check weekly after first dose to establish NADIR
If the neutrophil count at the NADIr is below ________ neutrophils/ul or the platelet count is below ______ platelets/ul, then the subsequent doses of the drug should be decreased by 20 to 25%
1500; 60,000
When neutrophils are < 1000/ul, you have myelosuppression. How should you manage these patients?
They are at risk for systemic infection —> prophylactic antibiotics
Common choices: clavamox, TMS
Most counts respond in 3-5days, severe cases need ICU
Granulocyte colony-stimulating factor stimulates marrow production (Rarely used )
You chemo patient has a thrombocytopenia <25,000/ul. How are you going to manage this patient?
Exercise restriction, close monitoring for bleeding (nose/GI)
Careful with Lomustine and melphalan
What is the MOA by which chemo causes GI toxicity?
Direct stimulation of chemoreceptor trigger zone in brain —> vomiting during first 24hrs of treatment
Damage to rapidly dividing cells of the crypts —> anorexia, vomiting, or diarrhea w/in 2-5days
** displaying and doxorubicin
What are the possible MOA of chemotherapy agents ?
Cell cycle specific
- antimitotics
- antimetabolites
Cell-cycle nonspecific
- alkylating agents
- antibiotics
What is the MOA of vinca alkaloids (vincristine/binblastine) and taxanes (paclitaxel and docetaxel)?
Antimicotic/microtubule toxins
—> disrupt or immobilize the mitotic spindle which plays critical role in cells function and division
What are the specific toxicities of Vincristine?
B. A. G
Vesicant
Neuropathy
Ileus
Vincristine is used to treat what tumors?
LSA
TVT
Vinblstine is used to treat what type of tumor and what is its main toxicity?
Mast cell tumor (MCT)
B.A.G
What should you do if you have extravasation of vincristine/blastine?
Dry warm compress
Hyaluronidase -> separate tissue planes and aids in improving absorption of drug into circulation
disperse and dilute
Chormabucil, cyclophosphamide, lomustine, melphalan are all what type of drug?
Alkylating agents
-> bind DNS and insert alkyl group to change structure of DNA sufficiently to interfere with transcription, replication and repair machinery
Melphalan treats wha tumor and has what main toxicity?
Myeloma
Bone marrow
Cyclophosphamide treats what tumor and has what main toxicity?
LSA
Bone marrow, alopecia
Sterile hemorrhagic cystitis
Lomustine (CCNU) treats what tumors and has what main toxicity?
LSA, MCT, histiocytotic sarcoma
Bone marrow and liver toxicity
Cholorambucil treats what tumors and has what main toxicity?
CLL (chronic lymphocytic leukemia) and low grade LSA (cat)
Bone marrow
Doxorubicin and mitoxantrone have what MOA?
Antibiotic agents
Doxorubicin (red death) is used to treat what tumors and has what main toxicities?
LSA, OSA, mesenchymal and epithelial tumors
GI and dose related cardiotoxicity
VESICANT
What do you do if you have doxorubicin extravasation?
DO NOT disperse
-localized and neutralize
Cold pack
DMSO
Sodium lactate
Mitoxantrone (blue thunder) is used to treat what tumors and has what main toxic effect?
TCC, LSA
Bone marrow and GI toxicity
Gemcitabine, 5-fluorouracil, and cytosine arabinoside have what MOA?
Antimetabolites
-> generally nucleotide analogs or substrates of active metabolic processes within the cell = S-phase
What are the usages of cytosine arabinoside?
CNS tumors and LSA
What is the MOA of carboplatin and cisplatin?
Platinum agents = covalent binding to DNS strands, forming inter strand cross linking which is cytotoxic
Cisplatin treats what tumors and has what main toxicities?
OSA in dog (NOT IN CAT)
Bone marrow and GI
Nephrotoxic
Carboplatin treats what tumors? Main toxic effect?
OSA and other sarcomas (ok in cats)
Bone marrow
MOA of L-asparaginase (ELSPAR) ?
Inhibit protein synthesis in cells by hydrolysis of L-asparginase to L-aspartic acid
Elspar is used to treat what tumor?
LSA release
- beware of hyper sensitivity rxn (no IV admin)
What is tanovea?
inhibit DNA synthesis in lymphocytes and LSA cell lines
—> st FDA approved lymphoma treatment for dogs
Common adverse rxns with Tanovea?
Neutropenia Diarrhea Anorexia Weight loss Lethargy Skin problems
What is metronomic chemotherapy?
All maximum tolerated dose (MTD) therapy requires a “break” period to allow for recovery of normal cells
-remaining viable tumor cells often exploit this time => recurrence
MC revolves around concept of eliminating break period by giving low dose continuous chemotherapy
Metronomic chemotherapy uses what MOA?
Antiangiogenesis
Immunomodulation
Direct targeting
What is the MOA of MC antiangiogenesis?
Prevent blood vessel proliferation required for tumor expansion by blocking COX and circulating endothelial progenitor cells
-> tumor endothelial cells proliferate rapidly during break period, thrombospondin -1 is present in tumor microenvironment (CYC)
What is the MOA of MC immunomodulation?
Immune effector cells ( lymphocyte and macrophages) in tumor microenvironment influence proliferation of tumor
T-regs normally INHIBIT immune response and suppress the host’s tumor surveillance (this is upregulated by cancer)
Immunomodulation decreases T-regs
What is the MOA of MC direct targeting?
Even though metronomic chemo (MC) is at lower dose, it has some direct effect on cancer cells
Direct kill also helps block angiogenesis
—> proangiogenic growth factors produced by tumor
—> direct killing of tumor cells if you decrease amount of GF (eg vascular endothelial growth factor, VEGF)
What alkylating agent is commonly used in MC protocols?
Cyclophosphamide
-inexpensive, low GI/hematologic toxicity
PO route
What unique adverse affect is associated with cyclophosphamide ?
Sterile hemorrhagic cystitis
Formation/accumulation of ACROLEN in urine —> submucosal edema, hemorrhage, necrosis, and fibrosis of musosal epithelium
How can you avoid sterile hemorrhagic cystitis (SHC)?
Environmental control - give in morning with free access to water and encourage frequent urination
Concurrent glucocorticoids/furosemide administration —> promote diuresis
What is the MOA of tyrosine kinase inhibitors?
Inhibition of tyrosine kinase receptors sends single to inhibit growth factor signals that allow the cells to divide
- also inhibit VEGFR2, PDGFRB, and stem cell factor receptor
What is Toceranib?
A tyrosine kinase inhibitor
Approved for used in Patnaik grade II or III, recurrent, cutaneous mast cell tumor with or without regional LN involvement
