Chemotherapy

Question 1

Stages of primary chemotherapy?

Answer 1

Induction - intensely scheduled initial treatments
(greatest chance of response, higher risk of toxicity).
Consolidation - end of induction (using unrelated, effective drugs to further reduce cancer cells)
Maintenance - less intense, using drugs already used in induction, may prolong time to relapse
Rescue - when drugs used in other phases no longer effective. Unrelated drugs (often alklylating bc they are less likely to show cross-resistance)

Question 2

When is nadir or peripheral neutrophil counts after myelosuppresive insult?

Answer 2

5 to 10 days after insult. Timing of myelosuppressive drug therapy is therefore every 2 to 3 weeks. Nadir less than 1000 neutrophils prompts 20-25% dose reduction.

Question 3

What is Neupogen, what are its indications?

Answer 3

human recombinate granulocute colony-stimulation factor (hr-G-CSF). Carries risk of induction of anticanine G-CSF antibodies. Practical use after inadvertent lethal chemo overdose.

Question 4

When do GI signs occur following chemotherapy?

Answer 4

3-5 days following treatment. 20 to 25% dose reduction is very unlikely to cause subsequent toxicity

Question 5

What drugs are particulary associated with anorexia in cats?

Answer 5

DOX and vincristine (may result in ileus). Cyproheptidine an megestrol acetate may stimulate appetite. Caution can cause DM in cats.

Question 6

What chemo drug is associated with cardiotoxicity?

Answer 6

DOX. Irreversible tox and carries poor to grave prognosis. End result resembles DCM and CHF.

Question 7

What is the primary dose-limiting toxicity of cisplatin?

Answer 7

nephrotoxicity in dogs. Causes acute fatal pulmonary edema in cats. Do not use in CATS!

Question 8

What specific toxicity is associated with cyclophosphamide and ifosamide in dogs?

Answer 8

sterile hemorrhagic cystitis. Drugs metabolized in liver to active form, results in production of acrolein metabolite which induces disease on contact of bladder mucosa.

Question 9

CCNU causes what kind of organ damage?

Answer 9

Hepatotoxicity. Can cause irreversible liver damage.

Question 10

What chemo drugs are associated with hypersensitivity reactions?

Answer 10

DOX (during administration can cause release of histamine from MCTs, result of too rapid admin), True anaphylaxis can occur with L-asparaginase (more so with IV, than IM, SQ)

Question 11

What chemo is specifically contraindicated in cats?

Answer 11

Cisplatin - fatal, acute pulmonary edema. 5-flurouracil -fatal nephrotoxicity.

Question 12

MOA for alkylating agents?

Answer 12

Create cross links in DNA, causing strand breaks. This group has lack of cross-resistance between different alkylating agents or with other classes of drugs?

Question 13

Examples of alkylating agents?

Answer 13

Nitrogen mustards (mechlorethamine, cyclophosphamide,ifosfamide, chlorambucil, melphalan). Nitrosoureas (lomustine (CCNU), streptozocin). Others (procarbazine, decarbazine)

Question 14

Indications for cyclophosphamide?

Answer 14

Lymphoma cats and dogs. PO or IV. Monitor CBC.

Question 15

Indications for chlorambucil?

Answer 15

Treatment of chronic lymphocytic leukemia or low grade lymphoma in dogs and cats. Substitute for cyclophosphamide if hemorrhagic cystitis occurs. PO. Monitor: CBC, myelosuppression can occur. Monitor liver enzymes

Question 16

Indications for melphalan?

Answer 16

Treatment of multiple myeloma in dogs and cats. PO. Monitor CBC.

Question 17

Indications for mechlorethamine?

Answer 17

Used in MOPP protocol for LSA in dogs and cats. IV (caution extravasation). Monitor CBC.

Question 18

Indications for procarbazine?

Answer 18

Used in MOPP protocol for LSA in dogs and cats. PO. Monitor CBC.

Question 19

Indications for CCNU?

Answer 19

Used in treatment of lymphoma, MCTs, brain tumors (gliomas, meningioma), malginant histiocytosis. PO. Leukopenia and thrombocytopenia expected (dose limiting). Potential hepatic and renal toxicities.

Question 20

MOA antitumor antibiotics?

Answer 20

DNA intercalation, interfers with topoisomerases and other mechs.
Can exhibit cross-resistance with other drugs (mediated by MDR drug efflux pump)”

Question 21

Examples of antitumor antibiotics?

Answer 21

Doxorubicin, mitoxantrone, actinomycin-D

Question 22

Indications for Doxorubicin?

Answer 22

Most active single agent in canine lymphoma. Highly effective combination for
lymphoma in dogs and cats. Treatment of solid tumors (esp OSA), and in combo
with cyclophosphamide. Monitor CBC, GI signs, liver function, ECG/Echo. Cats-renal. IV

Question 23

Indications for mitoxantrone?

Answer 23

Efficacious in combo with piroxicam for TCC in dogs. Moderate efficacy canine lymphoma, low in cats. Substitute for DOX in dogs at risk for cardiotox and cats
at risk for nephrotox. Monitor CBC. IV

Question 24

Indications for Actinomycin-D?

Answer 24

Alternative to DOX for canine lymphoma. Monitor CBC and GI signs. IV

Question 25

MOA for antimetabolites?

Answer 25

Inhibit the use of cellular metabolities in course of cell growth and division.

Question 26

Examples of antimetabolites?

Answer 26

Cytosine arabinoside, methotrexate, gemcitabin, 5-flurouracil

Question 27

Indications for cytosine arabinoside?

Answer 27

Infrequent component of combo therapy for leukemia and lymphoma in dogs and cats. Used if CNS involvement. IV or SQ.

Question 28

Indications for methotrexate?

Answer 28

Folate analog - inhibits enzymes dihydrofolate reductase, therefore decreases folate pools require for purine and thymidylate biosynthesis. Rarely used bit was in original multiagent tx of lymphoproliferative dz in cats and dogs. Oral

Question 29

Indications for gemcitabine?

Answer 29

MOA attributes to its incorporation into DNA and ultimate inhibition of DNA replication. Little evaluation but has had some reposnise in LSA, malignant melanoma, and SCC. Synergy with carboplatin in human med. IV

Question 30

Indications for 5-flurouracil?

Answer 30

Infrequenetly used for epithelial tumors (hepatic, pancreatic, renal, mammary). IV, topically, intralesionary.

Question 31

MOA for antimicrotubule agents?

Answer 31

Inhibit assembly of mitotic spindle

Question 32

Examples of antimicrotubule agents?

Answer 32

Taxanes (paclitaxel, docetaxel). Vinca alkaloids (vinblastine, vincristine)

Question 33

Indications for taxanes?

Answer 33

Requires signficant pre-treatment with antihistamines, steroids, long -effusion, to minimize acute hypersenstivity. Not evaluated well. Paclitaxel drug carrier is Cremophor EL, sobulizes drugs bit is highly allergenic. Less issues with docetaxil because no Cremophor EL.

Question 34

Indications for vinca alkaloids?

Answer 34

Vincristine - multiagent in dog and cats lymphoma, single agent for dogs with TVT. Vinblastine most often used to manage canine MCT, as single or multiagent. Vinorelbine - used in vareity of tumors but not thorughly evaluated yet.

Question 35

Indications and Moa for epipodophyllotoxins?

Answer 35

Inhibits topoisomerase II. Hypersentivity in dogs IV. Low oral bioavaliability. Not recommended for use in dogs. More studies needed in cats.

Question 36

MOA for platinum drugs?

Answer 36

Create cross-links in DNA. Similar to alkylating agents. No cross-resistance with other classes of drugs.

Question 37

Examples of platinum drugs?

Answer 37

Cisplatin, carboplatin.

Question 38

Indications for cisplatin?

Answer 38

Canine OSA, other carcinomas. Contraindicated in cats. Precede and follow with diuresis due to nephrotox. IV.

Question 39

Indications for carboplatin?

Answer 39

Similar to cisplatin with out renal tox and safe in cats. Monitor creatinine during treatment. IV.

Question 40

Indications of L-asparaginase?

Answer 40

used in combo for lymphoma in dogs (not as single agent due to rapid resistance). SQ or IM. Anaphylasis if given IV.

Question 41

Indications for hydroxyurea?

Answer 41

inhibits ribonucleotide reductase which decreases deoxyribonucleotides. Dosed orally. Used for treatment of bone marrow disorders such as polycythemia vera and granulocutic leukemias. Toxicities include GI effects, myelosuppression, onycholysis, pulmonary fibrosis.