Oncology

Question 1

Methotrexate (MTX)

Answer 1

1) CA: leukemia, lymphoma, choriocarcinoma, sarcoma; non-CA: abortion, ectopic preg, rheumatoid arthritis, psoriasis
2) folate analog: inhibits DHFR –> decr dTMP –> decr DNA + protein syn
3) myelosuppression (reverse w/ leucovorin); macrovesicular fatty liver change; mucositis; teratogenic
4) S-phase specific

Question 2

5-fluorouracil (5-FU)

Answer 2

1) colon CA, basal cell carcinoma (topical)
2) pyrimidine analog bioactivated to 5F-dUMP (covalently complexes folate) –> complex inhibits thymidylate synthase –> decr dTMP –> decr DNA + protein syn
3) myelosuppression (not reversible w/ leucovorin); OD rescue w/ thymidine; photosensitivity
4) S-phase specific

Question 3

Cytarabine (arabinofuranosyl cytidine)

Answer 3

1) leukemia, lymphoma
2) pyrimidine analog –> inhibit DNA polymerase
3) leukopenia, thrombocytopenia, megaloblastic anemia
4) S-phase specific

Question 4

Azathioprine

Answer 4

1) leukemias
2) purine (thiol) analog –> decr de novo purine syn
3) BM, GI, liver; metabolized by xanthine oxidase so incr toxicity w/ allopurinol
4) S-phase specific; activated by HGPRT

Question 5

6-mercaptopurine (6-MP)

Answer 5

1) leukemias
2) purine (thiol) analog –> decr de novo purine syn
3) BM, GI, liver; metabolized by xanthine oxidase so incr toxicity w/ allopurinol
4) S-phase specific; activated by HGPRT

Question 6

6-thioguanine (6-TG)

Answer 6

1) leukemias
2) purine (thiol) analog –> decr de novo purine syn
3) BM, GI, liver; metabolized by xanthine oxidase so incr toxicity w/ allopurinol
4) S-phase specific; activated by HGPRT

Question 7

Dactinomycin (actinomycin D)

Answer 7

1) Wilm’s tumor, Ewin’s sarcoma, rhabdomyosarcoma; peds tumors
2) intercalates in DNA
3) myelosuppression
4) N/A

Question 8

Doxorubicin (Adriamycin)

Answer 8

1) solid tumors, leukemias, lymphomas
2) makes ROS; non-covalently intercalate in DNA –> breaks DNA –> decr replication
3) cardiotoxicity* (dilated cardiomyopathy; use dexrazoxane, Fe chelator, to prevent), myelosuppression, alopecia; toxic to tissues following extravasation
4) N/A

Question 9

Daunorubicin

Answer 9

1) solid tumors, leukemias, lymphomas
2) makes ROS; non-covalently intercalate in DNA –> breaks DNA –> decr replication
3) cardiotoxicity* (dilated cardiomyopathy; use dexrazoxane, Fe chelator, to prevent), myelosuppression, alopecia; toxic to tissues following extravasation
4) N/A

Question 10

Bleomycin

Answer 10

1) testicular CA, Hodgkin’s lymphoma
2) ROS formation –> causes breaks in DNA strands
3) pulm fibrosis*, skin changes; minimal myelosuppression
4) N/A

Question 11

Cyclophosphamide

Answer 11

1) solid tumors, leukemia, lymphoma, some brain CAs
2) alkylating agent: covalently X-link DNA at guanine N-7
3) myelosuppression; hemorrhagic cystitis (partly prevent w/ mesna, thiol grp of mesna binds toxic metabolite)
4) need liver bioactivation

Question 12

Ifosfamide

Answer 12

1) solid tumors, leukemia, lymphoma, some brain CAs
2) alkylating agent: covalently X-link DNA at guanine N-7
3) myelosuppression; hemorrhagic cystitis (partly prevent w/ mesna, thiol grp of mesna binds toxic metabolite)
4) need liver bioactivation

Question 13

Carmustine

Answer 13

1) brain tumors (incl glioblastoma multiforme)
2) alkylating agent: nitrosourea
3) CNS toxicity: dizziness, ataxia
4) needs bioactivation; X’s BBB –> CNS

Question 14

Lomustine

Answer 14

1) brain tumors (incl glioblastoma multiforme)
2) alkylating agent: nitrosourea
3) CNS toxicity: dizziness, ataxia
4) needs bioactivation; X’s BBB –> CNS

Question 15

Semustine

Answer 15

1) brain tumors (incl glioblastoma multiforme)
2) alkylating agent: nitrosourea
3) CNS toxicity: dizziness, ataxia
4) needs bioactivation; X’s BBB –> CNS

Question 16

Streptozocin

Answer 16

1) brain tumors (incl glioblastoma multiforme)
2) alkylating agent: nitrosourea
3) CNS toxicity: dizziness, ataxia
4) needs bioactivation; X’s BBB –> CNS

Question 17

Busulfan

Answer 17

1) CML; also to ablate BM before BMT
2) alkylating agent
3) pulm fibrosis*; hyperpigmentation
4) N/A

Question 18

Vincristine

Answer 18

1) solid tumors, leukemias, lymphomas
2) microtubule inhibitor: alkaloid that binds to tubulin in M phase + blocks polymerization so mitotic spindle can’t form
3) neurotoxicity: areflexia, periph neuritis; paralytic ileus
4) N/A

Question 19

Vinblastine

Answer 19

1) solid tumors, leukemias, lymphomas
2) microtubule inhibitor: alkaloid that binds to tubulin in M phase + blocks polymerization so mitotic spindle can’t form
3) BM suppression (VinBLASTine BLASTS Bone Marrow)
4) N/A

Question 20

Paclitaxel

Answer 20

1) ovarian + breast carcinomas
2) microtubule inhibitor: hyperstabilizes polymerized microtubules in M phase so mitotic spindle can’t break down (blocks anaphase)
3) myelosuppression, hypersensitivity
4) N/A

Question 21

Cisplatin

Answer 21

1) testicular, bladder, ovary, lung carcinomas
2) X-links DNA
3) nephrotoxicity (prevent w/ amifostine, ROS scavenger), acoustic nerve damage, chloride diuresis
4) N/A

Question 22

Carboplatin

Answer 22

1) testicular, bladder, ovary, lung carcinomas
2) X-links DNA
3) nephrotoxicity (prevent w/ amifostine, ROS scavenger), acoustic nerve damage, chloride diuresis
4) N/A

Question 23

Etoposide

Answer 23

1) solid tumors, leukemias, lymphomas
2) topo II inhibitor –> incr DNA degradation
3) myelosuppression, GI irritation, alopecia
4) N/A

Question 24

Teniposide

Answer 24

1) solid tumors, leukemias, lymphomas
2) topo II inhibitor –> incr DNA degradation
3) myelosuppression, GI irritation, alopecia
4) N/A

Question 25

Hydroxyurea

Answer 25

1) melanoma, CML, sickle cell dz (incr HbF)
2) inhibits ribonucleotide reductase –> decr DNA syn (S-phase specific)
3) BM suppression, upset GI
4) N/A

Question 26

Prednisone

Answer 26

1) CA chemotx: CLL, non-Hodgkin’s lymphomas; immunosuppressant (autoimmune dz)
2) glucocorticoid; may trigger apoptosis; may work on non-dividing cells
3) Cushing-like sx’s; immunosuppression, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis
4) N/A

Question 27

Prednisolone

Answer 27

1) CA chemotx: CLL, non-Hodgkin’s lymphomas; immunosuppressant (autoimmune dz)
2) glucocorticoid; may trigger apoptosis; may work on non-dividing cells
3) Cushing-like sx’s; immunosuppression, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis
4) N/A

Question 28

Tamoxifen

Answer 28

1) breast CA tx + prophylaxis; prevent osteoporosis
2) SERM: R antagonist in breast + agonist in bone; block estrogen binding to ER+ cells
3) partial agonist in endometrium –> incr endometrial CA risk; “hot falshes”
4) compare toxicity to raloxifene

Question 29

Raloxifene

Answer 29

1) breast CA tx + prophylaxis; prevent osteoporosis
2) SERM: R antagonist in breast + agonist in bone; block estrogen binding to ER+ cells
3) no incr in endometrial carcinoma b/c it’s an endometrial antagonist
4) compare toxicity to tamoxifen

Question 30

Trastuzumab (Herceptin)

Answer 30

1) HER-2 (+) breast CA
2) monoclonal ab against HER-2 (c-erbB2), a tyrosine kinase –> kill breast CA cells taht overexpress HER-2 (ab-dependent cytotoxicity)
3) cardiotoxicity
4) N/A

Question 31

Imatinib (Gleevec)

Answer 31

1) CML, GI stromal tumors
2) Ph chr bcr-abl tyroxine kinase inhibitor
3) fluid retention
4) N/A

Question 32

Rituximab

Answer 32

1) non-Hodgkin’s lymphoma, rheumatoid arthritis (w/ MTX)
2) monoclonal ab against CD20 (found on most B-cell neoplasms)
3) N/A
4) N/A

Question 33

Vemurafenib

Answer 33

1) metastatic melanoma
2) small molec inhibitor of B-Raf kinases that have V600E mute
3) N/A
4) N/A

Question 34

Bevacizumab

Answer 34

1) solid tumors
2) monoclonal ab against VEGF –> inhibits angiogenesis
3) N/A
4) N/A