Antineoplastic Agents II

Question 1

Cyclophosohamide MOA
Uses (2)
Primary toxicity and antidote

Answer 1

Nitrogen mustard alkylating agent
Solid tumors and hematological malignancies
Hemorrhagic cystitis…antidote is mesna

Question 2

Carmustine (BCNU) MOA
Use
Primary toxicity

Answer 2

Nitrosource alkylating agent
Brain tumors (wafers and stuff)
Myelosuppression

Question 3

4 adverse effects of alkylating agents

Answer 3

1. Mutagenic
2. Myelosuppressive
3. Leukemia
4. Strong vesicant properties

Question 4

Common resistance mechanisms to alkylating agents

Answer 4

1. Inactivation by glutathione
2. Reduced uptake
3. Accelerated DNA repair
4. Increased expression of MGMT (removed alkyl groups from guanine)

Question 5

MOA of non-classical alkylating agents

Answer 5

Lead to DNA cross-linkages but do NOT have alkyl groups

Question 6

3 common non-classical alkylating agents (Platinum compounds)

Answer 6

1. Cisplatin
2. Carboplatin
3. Oxaliplatin

Question 7

Adverse effects of Cisplatin (2)

Answer 7

1. Peripheral motor and sensory neuropathy

2. Nephrotoxicity

Question 8

Primary differences between Cisplatin and Carboplatin (2)?

Answer 8

1. Carboplatin causes less nausea, neurotoxicity, ototoxicity, and nephrotoxicity than cisplatin
2. Dose-limiting toxicity for carboplastin is myelosuppresion

Question 9

Vinacristine MOA

Primary toxicity

Answer 9

Inhibits microtubule formation preventing mitotic spindle formation. This causes cell to arrest in mitosis causing cell death
Primary toxicity is neurological

Question 10

Vinablastine MOA

Primary toxicity

Answer 10

Inhibits microtubule formation preventing mitotic spindle formation. This causes cell to arrest in mitosis causing cell death
Primary toxicity is myelosuppresion

Question 11

Paclitaxel MOA

Primary toxicity

Answer 11

Kills tumor cells by preventing depolymerization of microtubules thereby arresting cells in mitosis
Primary toxicity is peripheral neuropathy

Question 12

What drug is commonly given with paclitaxel to reduce myelosuppression?

Answer 12

Filgrastin (G-CSF)

Question 13

Topoisomerase I inhibitors (2)

Topoisomerase II inhibitor

Answer 13

1. Irinotecan and Topotecan

2. Etoposide

Question 14

Doxorubicine MOAs (2)
Primary toxicity and antidote

Answer 14

1. Intercalates with DNA and inhibits topoisomerase II thereby causing DNA damage
2. Also binds to iron and generates free radicals which cause DNA and protein damage
3. Primary toxicity is irreversible cardiomyopathy. Antidote is dexrazoxane

Question 15

Bleomycin MOA

Primary toxicity

Answer 15

1. Small peptide that binds to DNA and causes single and double strand breaks. It causes cells to arrest in G2
2. Primary toxicity is irreversible pulmonary toxicity

Question 16

Prednisone and dexamethasone MOA for cancer

Answer 16

Inhibit lymphocyte proliferations and decreases intracranial pressure

Question 17

Tamoxifen MOA

Primary toxicity

Answer 17

Partial competitive estrogen receptor antagonist that decreases growth of estrogen dependent breast cancers

Patients are at increased risk of endometrial cancer

Question 18

Anastrozole MOA

Answer 18

Aromatase inhibitor which lowers estrogen levels

Question 19

Flutamide MOA

Answer 19

Prevents dihydrotestosterone from binding to androgen receptors. Useful for prostate cancers

Question 20

GnRH agonists

GnRH antagonist

Answer 20

Leuprolide an goserelin are GnRH agonists

Degarelix is an GnRH antagonist

Question 21

Trastuzumab MOAs (2)
Primary toxicity

Answer 21

HER-2 inhibitor and blocks HER-2 mediated signaling. Can also induce antibody dependent cytotoxicity
Toxicity: Irreversible cardiac toxicity (CHF)

Question 22

Cetuximab MOA

Primary use

Answer 22

Monoclonal antibody that binds to EGFR and blocks signaling.

Useful for colorectal cancers

Question 23

Bevacizumab MOA

Answer 23

Monoclonal antibody directed against VEGF…prevents angiogenesis

Question 24

Lapatinab MOA

Primary use

Answer 24

Small molecule that inhibits both EGFR and HER-2 kinase activity.
Used to treat HER-2 amplified, trastuzumab-refractory breast cancer

Question 25

Erlotininb | Primary use

Answer 25

Oral, small molecule EGFR inhibitor | First line treatment of metastatic nonsmall cell lung carcinoma with EGFR mutations at exon 19 or 21

Question 26

Imatinib MOA Primary use Resistance mechanism

Answer 26

Small molecule inhibitor of BCR-ABL and thereby inhibits growth signaling Treats chronic myelogenous leukemia caused by Philadelphia chromosome translocation Point mutations in BCR-ABL cause a reduced affinity for Imatinib

Question 27

Asparaginase MOA Use Adverse effect

Answer 27

Hydrolyzes L-asparagine into L-aspartate Treats Acute Lymphoblastic leukemia (ALL) Primary adverse effect is allergic reaction

Question 28

Bortezomib MOA Use Toxicity

Answer 28

Inhibits proteasome causing increases in p53 Treats relapsed or refractory multiple myeloma Peripheral neuropathy

Question 29

Temsirolimus MOA | Use

Answer 29

Inhibition of mTOR complex 1 which reduces protein translation, promotes cell cycle inhibition, and promotes apoptosis Treats renal cell carcinoma