CHAPTER 35: ANTICANCER DRUGS

Question 1

Antimetabolites

Answer 1

• folic acid analogs: methotrexate
• pyrimidine analogs: 5-fluorouracil
• purine analogs: 6-mercaptopurine

Question 2

Methotrexate: MOA

Answer 2

• antifolate
• folic acid role in metabolic rxns and cell replication

MOA: inhibit DHFR, enz that converts folic acid to active form FH4

Question 3

Methotrexate: therapeutic use

Answer 3

• combo w other drugs
• acute lymphocytic leukemia, burkitt lymphoma in CHILDREN
• bladder cancer
• head/neck carcinomas
• low dose single agent for inflamm diseases (arthritis, psoriasis, Crohns)

Question 4

Methotrexate: adverse effects and drug-drug interactions

Answer 4

AE: rash, alopecia, myelosuprresion, stomatitis
high dose AE: renal damage

drug-drug: omeprazole, folic acid, warfarin, NSAIDs, penicillin

Question 5

Antitumor Antibiotics
- names
- how does it work
- cell cycle specific?

Answer 5

• doxorubicin
• interfere w DNA synth, insert between base pairs (intercalation)
• inhibit topoisomerase too ( form free radicals)
• cell cycle phase nonspecific

Question 6

Doxorubicin: therapeutic uses

Answer 6

• combo for sarcomas and carcinomas
• breast cancer
• acute lymphocytic leukemia
• lymphomas

Question 7

Doxorubicin: MOA

Answer 7

• free radicals can induce membrane lipid peroxidation, DNA strand scission
• oxidation purine/pyrimidine bases, thiols and amines

Question 8

Doxorubicin: Adverse effects

Answer 8

• bone marrow suppressin
• GI disturbances
• tissue damage/extravasation
• alopecia
• cardiotoxicity
• RED color urine and sweat

Question 9

Doxorubicin: drug interactions

Answer 9

• calcium channel blockers (inc cardiotox)
• phenobarbital (inc metab doxo)
• paclitaxel (dec metab doxo)
• phenytoin levels reduced

Question 10

Microtubule Inhibitors
- names
- how does it work
- cell cycle specific?

Answer 10

• vinca alkaloids (vincristine/vinblastine)
• taxanes (paclitaxel)
• stop cell division during mitosis, affect equilibrium of polymerized and depolym forms of the microtubules
• M phase cell cycle specific

Question 11

Vincristine and Vinblastine

Answer 11

• USED AS COMBO w other drugs

Vincristine: treat acute lymphoblastic leukemia in children, wilms tumor, soft tissue sarcoma, Hodgkin lymphomas

Vinblastine: give w bleomycin and cisplatin to treat metastatic testicular carcinoma
- treat hodgkin lymphomas

Question 12

Vincristine and Vinblastine: MOA

Answer 12

bind to microtubular protein, tubulin
- block tubulin to polymerize and form microtubules
- aggregates consisting of tubulin dimers and drug are formed–> dysfunc spindle apparatus, freeze in metaphase, prevent chromosome segregation and cell proliferation

Question 13

Vincristine and Vinblastine: adverse effects

Answer 13

• phlebitis or cellulitis (from extravasation)
• nausea, vomit, diarrhea, alopecia

Vinblastine: myelosuppression

Vincristine: peripheral neuropathy (paresthesia, loss reflex, ataxia), and constipation

DO NOT deliver intratheca

Question 14

Noncytotoxic Agents: steroid hormones and antagonists

tumors sensitive to steroid hormones can be…

Answer 14

• hormone responsive: tumor regress following treatment w specific hormone
• hormone dep: removal of hormone stimulus causes tumor regression
• BOTH

Question 15

Noncytotoxic Chemo agents: agonists vs antagonists

Answer 15

Agonists: GnRH (gonadotropin releasing hormone)
Antagonists: anti estrogen for estrogenic dep cancer, anti testosterone for test. dep cancer

Question 16

Hormonal Agents- Prostate Cancer
- GnRH

Answer 16

• Leuprolide
• occupy GnRH receptor in pituitary–> desensitize–> inhibit release FSH and LH
• testes stop producing testosterone

Question 17

Hormonal Agents- Prostate Cancer
- Androgen Receptor Antagonists

Answer 17

• flutamide
• block testosterone at receptor site

Question 18

Hormonal Agents- Prostate Cancer
- leuprolide AE and contraindications

Answer 18

AE: hot flash, dec libido, gynecomastia, dec bone density, arrhythmia, pulm edema

contraindicate: PT w hypersensitivity

Question 19

Hormonal Agents- Prostate Cancer
-Flutamide AE, contraindications, interactions

Answer 19

AE: hot flash, dec libido, gynecomastia, GI disturbances, hepatitis

contraindicated: PT w liver disease
interactions: warfarin (inc anticoag effect)

Question 20

Hormonal Agents- Breast Cancer
- estrogen receptor antag

Answer 20

• tamoxifen
• stop breast cancer growth
• first live treat and prevention

Question 21

Hormonal Agents- Breast Cancer
- Aromatase Inhibitors

Answer 21

• anastrozole
• stop growth by blocking estrogen production
• first line in postmenopausal women

Question 22

Hormonal Agents- Breast Cancer
- monoclonal antibody

Answer 22

• trastuzumab
• prevent growth by causing cell death
• treat metastatic breast cancer
• along OR combo w paclitaxel

Question 23

Hormonal Agents: Breast Cancer
ADVERSE EFFECTS AND CONTRAINDICATIONS

TAMOXIFEN

Answer 23

• AE: endometrial cancer, hypercalcemia, nausea/vomit, pul embolus, hot flash, vag discharge/bleeding
• contraindicated: pregnancy, PT taking warfarin, history of blood clots or pulm embolism

Question 24

Hormonal Agents- Breast Cancer
ADVERSE EFFECTS AND CONTRAINDICATIONS

ANASTRAZOLE

Answer 24

• AE: muscle/joint pain, osteoporosis, nausea, hot flash
• contraindicated: pregnancy, women before menopause, PT liver disease

Question 25

Hormonal Agents- Breast Cancer
ADVERSE EFFECTS AND CONTRAINDICATIONS

TRASTUZUMAB

Answer 25

• AE: cardiac toxicity, tachy, HF, hypersensitivity, nausea/vomit
• contraindicated: pregnancy, hypersensitive PT, heart disease PT

Question 26

Antibodies treatment: EGFR Tyrosine kinase inhibitors

Answer 26

• cetuximab
• inhibit epidermal growth factor receptor
• treat metastatic colorectal cancer, metastatic non small cell lung cancer, head/neck cancer

Question 27

Antibodies treatment: CD20 directed antibodies

Answer 27

• rituximab
• antibody against protein CD20, on surface of immune sys B cells
• binds to protein and trigger cell death
• treat various cancers, ex) non hodgkins lymphoma

Question 28

Antibodies treatment: angiogenesis inhibitors

Answer 28

• bevacizumab
• block angiogenesis, inhibit vascular endothelial growth factor A (VEGF-A)
• treat colorectal and lung cancers