Chemotherapeutics

Question 1

Trastuzumab (Herceptin)

Answer 1

Monoclonal Antibody: against HER2. For HER2 positive breast cancer (HER2 gene encodes growth factor HER2 - overexpressed in 25-30% breast cancers). Use in combination with chemo, improves outcomes.

Question 2

Imatinib (Bleevec)

Answer 2

Tyrosine kinase (TK) inhibitor. For sustained remission of chronic myeloid leukemia (CML). Inhibits abnormal TK that drives proliferation. Tx: nausea, vomiting, diarrhea, edema, muscle cramps, rash, neutropenia, thrombocytopenia.

Question 3

Gefitinib (Iressa)

Answer 3

TK inhibitor. Blocks growth signals mediated by TK (especially TK associated w/ EGF). For advanced non-small cell lung cancer. Only 10% of patients responsive, so identify people w/ EGF gene mutation.

Question 4

Bevacizumab (Avastin)

Answer 4

Antibody. Targets VEGF. Inhibits angiogenesis.

Question 5

Sunitinib (Sutent)

Answer 5

TK inhibitor. NEW! Targets VEGF. Inhibits angiogenesis.

Question 6

Sorafenib (Nexavar)

Answer 6

Similar to Sunitinib. Inhibits angiogenesis.

Question 7

Suberoylanilide Hydroxamic Acid (Vorinostat)

Answer 7

Histone deacteylase inhibitor (HDACi). Keeps histones acetylated and transcriptionally active to reactivate down regulated tumor suppressor genes. Inhibits cancer growth epigenetically

Question 8

Azacytidine and Decitabine

Answer 8

Inhibit DNA methylation (Epigenetic) - Reactivate down regulated tumor suppressor genes. Inhibits cancer growth.

Question 9

Methylguanine Methyltransferase (MGMT)

Answer 9

Repairs alkylating damage to DNA. Helps repair normal cells. glioblastomas w/ methylated (silenced) MGMT more likely to have successful treatment by Temozolomide

Question 10

Temozolomide

Answer 10

Alkylating agent. Damages DNA to kill cancer cells esp. glioblastoma. Use w/ methylated MGMT to make more responsive

Question 11

Sarcosine

Answer 11

Amino acid (derivative of glycine). Potentially important metabolic intermediary of prostate cancer cell invasion and metastasis. Measure for aggressiveness. Tells whether someone will need aggressive treatment or not. Lowest in BPH, higher in Prostatic Cancer, Highest with Metastasis.

Question 12

Serotonin receptor antagonists: Dolasetron (Anzemet) and Palonosetron (Aloxi, T1/2=40 hrs.)

Answer 12

Prevent nausea and vomiting from chemo. Side effects: headache, dizzyness, diarrhea, constipation

Question 13

Corticosteroids: Dexamethasone

Answer 13

Prevent nausea and vomiting from chemo.

Question 14

Chlorambucil

Answer 14

Alkylating agent. Non cycle active. Abs. Oral. Least toxic alkylating agent. For chronic leukemias. Non cycle active.

Question 15

Cyclophosphamide

Answer 15

Alkylating agent. Non cycle active. Requires metabolic activation by liver. Tx: Hair loss, liver tx.

Question 16

Carmustin (BCNU)

Answer 16

Alkylating agent. Non cycle active. Abs. IV. Lipid soluble - Dist. to CSF for CNS tumors.

Question 17

Busulfan

Answer 17

Alkylating agent. Non cycle active. For myelosuppression. Tx: Little to GI.

Question 18

Gemcitabine

Answer 18

Non cycle active. Inhibits DNA synthesis, and alters DNA template. Effective agains solid tumors.

Question 19

Methotrexate (MTX)

Answer 19

Antimetabolite: Folic acid analog. Inhibits dihydrofolate reductase which decreases THF, thereby inhibiting 1 C transfers and DNA synthesis. Renal E. Contraindicated in people w/ renal function impairment. Cycle active drug.

Question 20

Folinic Acid

Answer 20

Recues MTX induced host toxicity. Metabolizes to THF w/o using dihydrofolate reductase.

Question 21

6-Mercaptopurine and Thioguanine

Answer 21

Purine analogs. Inhibit multiple steps in purine nucleotide synthesis. Must be metabolized to be active, then inhibit IMP. Cycle active, decrease DNA synthesis.

Question 22

5-Fluorouracil (5-FU)

Answer 22

Pyrimidine analog. Must be metabolized into mono-P. Inhibits thymidylate synthetase conversion of dUMP to TMP. Cycle active, decreases DNA synthesis. Tx: Hair loss

Question 23

Cytarabine

Answer 23

Pyrimidine analog. Must be metabolized into mono-P.

Question 24

Paclitaxel (Taxol), Vincristine, Vinblastine

Answer 24

Block mitosis (cycle active), metaphase arrest.
Vincristine: remission, acute leukemia. Tx: Minimal myelosuppression (good), CNS: progressive, cumulative, weakness, tremors, convulsions
Vinblastine: solid tumors, Hodgkins disease, testicular tumors. Tx: Myelosuppression, less neuro toxicity (good).

Question 25

Etoposide

Answer 25

Non cycle active (from mandrake plant). Inhibits topoisomerase, causes DNA strand breaks. For testicular cancer.

Question 26

Topotecan

Answer 26

Non cycle active. Topoisomerase inhibitor (like fluoroquinolones), cuases DNA double strand breaks. For ovarian and lung cancer.

Question 27

Actinomycin D

Answer 27

Natural product. Inhibits RNA synthesis (RNA polymerase), non cycle active. For solid tumors. Tx: Very toxic especially bone marrow, and immunosuppression.

Question 28

Bleomycin

Answer 28

Natural product. Mixture of related drugs. DNA strand breaks. Non cycle active. For solid tumors, testicular cancer, and lymphomas. Tx: Pulmonary fibrosis (2-5%).

Question 29

Doxorubicin (Adriamycin)

Answer 29

Natural product. Inhibits topoisomerases. Tx: Cardiac: arrythmias/CHF, which are minimized by monitoring blood levels, and hair loss.

Question 30

Mitomycin

Answer 30

Natural product. Alkylating agent. For solid tumors.

Question 31

Prednisone

Answer 31

Corticoid (steroid). Anti cancer.

Question 32

Tamoxifen

Answer 32

Antiestrogen. Metabolized in liver (CYP2D6) to endoxifen (active). Decreased metabolism if taken w/ antidepressants (Paxil, Prozac). Pharmacogenetics important: Person must express CYP2D6.

Question 33

Exemestane and Anastrozole

Answer 33

Aromatase inhibitors. Inhibit metabolism of androstenedione to estrone which is then metabolized to estradiol. Decreases levels of estrogen (good for estrogen producing tumors)

Question 34

Flutamide and leuprolide

Answer 34

Antiandrogens. Flutamide: Abs. oral. For metastatic prostate cancer. May prolong life. Only used with leuprolide (LHRL analog) or bilateral orchiectomy. Blocks uptake of androgens, prevents adrenal androgens. Tx: gynecomastia (frequent), nausea and vomiting (occasional).

Question 35

Cisplatin (Oxaplatin/carboplatin = newer members)

Answer 35

Contains Pt. Like alkylating agent. Non cycle active. Abs. IV. Urine E. Tx: Renal tx, minimized by hydration, and manitol diuresis. For solid tumors: head/neck, ovarian, bladder, testicular.

Question 36

Hydroxyurea

Answer 36

Cycle active. Inhibits ribonucleotide reductase, which inhibits formation of deoxyribonucleotides, which inhibits DNA synthesis (specifically against purines).