Chemo Agents

Question 1

What are the general mechanisms of action of chemo agents?

Answer 1

Targeting the cell cycle and biology of tumor growth

Question 2

In order for chemo to work, cancer cells must be more/less sensitive to the drugs than normal tissue?

Answer 2

More; rely on normal tissue to be able to respond appropriately and recover

Question 3

Which are the phase-specific chemo agents?

Answer 3

Vincristine, Vinblastine (M), Cytosine arabinoside (Cytosar), Methotrexate (S)

Question 4

Which are the phase non-specific agents?

Answer 4

• Alkylating agents
• Nitrosoureas
• Antitumor antibiotics
• Procarbazine
• Platinum derivatives

Question 5

What is the most commonly use and largest group of chemo agents?

Answer 5

Alkylating agents

Question 6

Carboplatin

Answer 6

Classification: Alkylating agent

Non-phase specific

MOI: crosslinks DNA, inhibits protein synthesis

Toxicity: myelosuppression, monitor platelets

SAFE FOR CATS, fewer GI SE

Question 7

Antimetabolites

Answer 7

• Cell cycle phase specific- S phase
• MOI: Cuts out folate in cell cycle; inserted into DNA and non-functional
• Agents: Methotrexate, cytosine arabinoside (Cytosar)
• Cross BBB

Question 8

Methotrexate

Answer 8

Classification: Antimetabolite

Cell cycle phase specific- S phase

MOI: Cuts out folate in cell cycle; inserted into DNA and non-functional

Uses: lymphoma, CNS tumors, osteosarcoma

Toxicity: GI and myelosuppression

Question 9

Cytosine Arabinoside (Cytosar)

Answer 9

Classification: Antimetabolite

Cell cycle phase specific- S phase

MOI: Cuts out folate in cell cycle; inserted into DNA and non-functional

Uses: renal lymphoma, lymphoma rescue, CNS tumors

Toxicity: none mentioned, efficiently removed from circulation by the kidney

Question 10

Antibiotic Chemo Agents

Answer 10

Cell cycle phase nonspecific

MOA: free radical damage, inhibition of topoisomerase II

Agents: Doxorubicin, Actinomycin D, Mitoxantrone

Question 11

Doxorubicin

Answer 11

Classification: Antibiotic

Cell cycle phase nonspecific

MOA: free radical damage, inhibition of topoisomerase II

Uses: lymphoma, osteosarcoma, hemangiosarcoma

Toxicity: anaphylaxis, vesicant, cardiotoxicity

Question 12

Mitoxantrone

Answer 12

Classification: Antibiotic

Cell cycle phase nonspecific

MOA: free radical damage, inhibition of topoisomerase II

Uses: LSA rescue, TCC, thymomas

Toxicity: myelosuppression, GI

Question 13

Actinomycin D

Answer 13

Classificiation: Antibiotic

Cell cycle phase nonspecific

MOA: free radical damage, inhibition of topoisomerase II

Uses: lymphoma rescue, non-cardiotoxic substitute for Doxorubicin

Toxicity: myelosuppression and GI

Question 14

Plant Alkaloids

Answer 14

Cell cycle phase specific - M phase

MOI: Bind microtubules, prevent assembly/disassembly

Agents: Vincristine, Vinblastine, Vinorelbine, Taxanes

Question 15

Vincristine

Answer 15

Classification: Plant Alkaloid

Cell cycle phase specific - M phase

MOI: Bind microtubules, prevent assembly/disassembly

Uses: lymphoma (combo protocols), transmissible venereal tumor, thrombocytopenia

Toxicity: vesicant, myelosuppression, peripheral neuropathy

Question 16

Vinblastine

Answer 16

Classification: Plant alkaloid

Cell cycle phase specific - M phase

MOI: Bind microtubules, prevent assembly/disassembly

Uses: Mast cell tumor, sub for vincristine if neuropathy suspected

Toxicity: vesicant, myelosuppression (> vincristine)

Question 17

Hormones

Answer 17

• Agents: Prednisone
• MOA: bind to cytoplasmic receptors & inhibit DNA synthesis
• Uses: lymphoma, mast cell tumor, insulinoma, intracranial neoplasia
• Toxicity: PU/PD, polyphagia, panting, GI ulcers

DO NOT USE CONCURRENTLY WITH NSAIDS

Question 18

Enzymes

Answer 18

Cell cycle phase nonspecific - max G1 phase activity Agents: L-asparaginase

Question 19

L-asparaginase

Answer 19

Classification: Misc. Enzyme

Cell cycle phase nonspecific - max G1 phase activity

MOI: Breaks down asparagine w/o which cancer cells cannot make DNA

Uses: lymphoma

Toxicity: anaphylaxis!, potentiate vincristine-induced myelosuppression, pancreatitis; Alone NOT myelosuppressive

Question 20

Receptor-Tyrosine Kinase Inhibitors

Answer 20

Targeted therapy - only in vet med!

Toceranib and Masitinib

MOA: targets RT-kinases

Uses: Mast cell tumors

Toxicity (KIT): bone marrow, GI, skin, renal Also Masitinib (Kinavet) - not found in US

Question 21

Tanovea

Answer 21

Classification: Targeted Therapy

MOA: prodrug - active phosphorylated form = potent inhibitor of replicative DNA polymerases

Uses: canine lymphoma (1st FDA approved tx)

Toxicity: Decr WBC count, diarrhea, vomiting, decreased/loss of appetite, weight loss, skin problems, pulmonary fibrosis in dogs (NOT USED IN WESTIES)

Question 22

Describe alkylating agents

Answer 22

• Largest group of chemo agents
• Cell cycle non-specific
• MOI: cross-link DNA, inhibit protein synthesis
• Class cross-resistance
• All derivatives of nitrogen mustard (mustard gas)

Question 23

What do we associate with cytotoxicity of alkylating agents?

Answer 23

Inter-strand crosslinking

Question 24

Cyclophosphamide

Answer 24

• Classification: Alkylating agent
• Non-phase specific
• MOI: crosslinks DNA, inhibits protein synthesis
• Uses: lymphoma, hemangiosarcs, STS
• Toxicity: myelosuppresion, sterile hemorrhagic cystitis***, GI

Question 25

What is the active ingredient that causes cystitis?

Answer 25

Acrolein

Question 26

Chlorambucil

Answer 26

* Classification: **Alkylating agent** * **Non-phase specific** * **MOI**: crosslinks DNA, inhibits protein synthesis * **Uses**: _multiple myeloma_ (most common), substitute for Cytoxan, chronic lymphocytic leukemia, feline GI (small cell) lymphoma * **Toxicity**: mild myelosuppression, GI * KEEP COLD!

Question 27

Lomustine

Answer 27

Classification: **Alkylating agent** MOI: cross links DNA **Non-phase specific** **Uses:** LOPP rescue protocol **Toxicity**: myelosuppressive and hepatotoxic (alpha-lipoic acid and Denamarin are protectants), Neutropenia nadir variable (immunosuppressive)

Question 28

Procarbazine

Answer 28

Classification: **Alkylating agent** **Non-phase specific** **MOI**: crosslinks DNA, inhibits protein synthesis **Uses:** LOPP/MOPP rescue protocol Toxicity: none?

Question 29

Cisplatin

Answer 29

Classification: **Alkylating agent** **Non-phase specific** **MOI:** crosslinks DNA, inhibits protein synthesis **Uses**: osteosarcoma, squamous cell carcinoma, equine sarcoids **Toxicity**: nephrotoxic (diurese), nausea, **_fatal pulmonary edema in cats_**

Question 30

Melphalan

Answer 30

Classification: **Alkylating agent** **Non-phase specific** **MOI:** crosslinks DNA, inhibits protein synthesis **Uses:** multiple myeloma, lymphoma rescue **Toxicity:** myelosuppression (thrombocytopenia), GI