Anticancer Drugs

Question 1

Malignant

Answer 1

Tumor invades nearby tissue or spreads throughout the body

Question 2

Anticancer drug classes

Answer 2

Cytotoxic drugs, hormonal drugs and targeted drugs

Question 3

Cytotoxic Drug Toxicity Impacts on body systems

Answer 3

• Bone marrow: Neutropenia (decrease WBC’s) which results in infections. Fever. The “nadir”, Thrombocytopenia (decrease in platelets)
• Hair follicles: Alopecia
• GI tract: stomatitis, diarrhea, nausea and vomiting
• Gonads: menstrual irregularities and impaired spermatogenesis
• Wounds: impaired healing
• Fetus: teratogenesis

Question 4

Cytotoxic Drug Therapy

Answer 4

Combination drug therapy is most effective: less drug resistance, increased effectiveness, less toxic to normal cells because drugs with non overlapping toxicities are used

Question 5

Hodgkins Drug Therapy

Answer 5

ABVD- adriamycin, bleomycin, vinblastine, decarbazine

Question 6

Breast Cancer Drug Therapy

Answer 6

CMF- cyclophosphamide, methotrexate, 5-fluorouracil

Question 7

Cytotoxic drug types or classes

Answer 7

Alkylating agents, platinum compounds (alkylating “like”), antimetabolites, anti tumor antibiotics, mitotic inhibitors, topoisomerase inhibitors, miscellaneous cytotoxic drugs

Question 8

Alkylating Agents

Answer 8

• CYCLOPHOSPHAMID, CISPLATIN (alkylating “like”)
• Highly reactive compounds
• Cells killed by alkalization of DNA

Question 9

Cyclophosphamide

Answer 9

• Used orally and IV with a half life of 7 hours

- Requires activation in the liver to activate metabolites. Suppresses the immune system

Question 10

Adverse Effects and Uses of Cyclophosphamide

Answer 10

Bone marrow suppression, nausea and vomiting, alopecia, sterility, immunosuppression, hemorrhagic cystitis, bladder toxicity, Mesna as an antidote
Uses: leukemia, lymphoma, multiple myeloma; breast, lung, ovarian, neuroblastoma, retinoblastoma, sarcoma,

Question 11

Cisplatin-Alkylating like agent

Answer 11

• Platinum-guanine DNA crosslinking
• Used by IV infusion
• Adverse effects: nausea and vomiting, bone marrow suppression, irreversible HEARING loss (ototoxicity), peripheral neuropathy, use is limited by renal toxicity which is treated with fluid and diuretics
• Uses: testicular, ovarian, bladder, lung, head and neck cancers

Question 12

Cochlear explants cultures

Answer 12

Protection of hair cells in the inner ear from cisplatin-induced death

Question 13

Antimetabolites

Answer 13

Drugs that resemble natural substrate molecules and inhibit or substitute for those molecules to interfere with DNA or RNA synthesis groups include: PYRIMIDINE ANALOGS-5-fluorouracil
PURINE ANALOGS- 6 mercaptopurine

Question 14

Antitumor Antibiotics-DOXORUBICIN

Answer 14

Only used IV to treat cancer
MOA: Inserts into DNA
-Used to treat many tumor types: Hodgkin’s, cancers of lung, ovary, breast, thyroid, testes
- Can cause acute (arrhythmias) and delayed, months to years, (heart failure) cardiac toxicity. Vesicant

Question 15

Mitotic Inhibitors

Answer 15

MOA: Block mitosis by inhibiting microtubules that move chromosomes during cell division, given IV
Vincristine and Paclitaxel

Question 16

Vincristine

Answer 16

Causes peripheral nerve toxicity but little bone marrow depression. Common use in combo cancer therapy. Vesicant

Question 17

Paclitaxel

Answer 17

Commonly used, ovarian and lung cancer. Causes bone marrow suppression, peripheral neuropathy and cardiac toxicity

Question 18

Topoisomerase Inhibitors

Answer 18

Etoposide and Asparaginase (enzyme)

Question 19

ETOPOSIDE

Answer 19

Etoposide inhibits topoisomerase. Topoisomerase alters the shape of supercoiled DNA to allow replication and repair. This drug causes hypotension, dilute in large volume of i.v. fluid

Question 20

ASPARAGINASE

Answer 20

Converts asparagine to aspartic acid which depletes the amino acid asparagine inhibiting protein synthesis. Only LEUKEMIC cells.
Atypical adverse: altered blood coagulation, liver and kidney damage, immune hypersensitivity reactions. NO BONE MARROW EFFECTS

Question 21

TAMOXIFEN

Answer 21

Antiestrogens block estrogen receptors in breast tumors (ER +) in women and men.
MOA: blocks estrogen receptors in some tissues (breast) but stimulates those receptors in other tissues (bone and liver). Selective estrogen receptor modulator

Question 22

Adverse Effects of Tamoxifen

Answer 22

Menstrual irregularities, hot flashes, thromboembolism (deep vein thrombosis), endometrial cancer risk, may cause damage to developing embryos

Question 23

Aromatase Inhibitors-Letrozole, Anastrozole and Exemestane

Answer 23

MOA: block synthesis of estrogen from androgens
Oral drugs. Treatment for 5 years.
Adverse: musculoskeletal pain is common, hot flashes, GI disturbances, osteoporosis

Question 24

Trastuzumab

Answer 24

• Human epidermal growth factor receptor 2 (HER2) monoclonal antibody
• Trastuzumab binds to HER2 to inhibit cell growth and causes antibody induced cell death
• Adverse effects: cardio toxicity, fatal hypersensitivity reactions, flu like symptoms (40%)

Question 25

Hormonal Drugs for Prostate Cancer

Answer 25

• Prostate glands tumors require androgen for tumor growth

- Prostate cancer drugs include: Gonadotropin releasing hormone antagonists, androgen receptor blockers

Question 26

GnRH Antagonists

Answer 26

• Degarelix is a GnRH antagonist. Blocks GnRH receptors and inhibits FSH and LH hormones release, thus blocking testes production of androgens
• Adverse effects: hot flashes, loss of libido, gynecomastia, reduced muscle mass, osteoporosis

Question 27

Androgen Receptor Blockers

Answer 27

Flutamide- oral
MOA: blocks androgen receptors in tumor cells to inhibit androgen dependent cell growth
Adverse: hot flashes, loss of libido, gynecomastia, reduced muscle mass, osteoporosis, liver failure

Question 28

Gefitinib or Erlotinib

Answer 28

MOA: small molecules which block an enzyme called tyrosine kinase thus suppressing cell proliferation and promoting apoptosis
Indication: cancer resistant to cisplatin or paclitaxel therapy
Adverse: GI, skin rash