From Jen: Onc1

Question 1

Drugs affecting nucleotide synthesis

Answer 1

Methotrexate
5-fluorouracil
(decrease thymidine synthesis)

6-mercaptopurine
(decrease purine synthesis)

Question 2

Drugs affecting DNA

Answer 2

Alkylating agents:
Cisplatin
(Cross-link DNA)

Dactinomycin
Doxorubicin
(Intercalate DNA)

Etoposide
(inhibit topoisomerase II)

Question 3

Drugs affecting cellular division

Answer 3

Vinca alkaloids (inhibit microtubule formation)

Paclitaxel (inhibit microtubule disassembly)

Question 4

Methotrexate

Answer 4

MTX

MOA: S-phase specific antimetabolite; folic acid analog that inhibits DHF reductase resulting in decreased dTMP

Use: leukemias, lymphomas, choriocarcinoma, sarcoma, ectopic pregnancy, abortion, RA, psoriasis

Adverse: myelosuppresion (reversible with leucovorin), microvascular fatty change in liver, mucositis

Question 5

5-fluorouracil

Answer 5

5-FU

MOA: S-phase specific antimetabolite. Pyrimidine analog activated to 5F-dUMP, which covalently complexes folic acid. The complex inhibits thymidylate synthase
synergistic with MTX

Use: Colon cancer, other solid tumors, basal cell carcinoma

Adverse: myelosuppression (irreversible), photosensitivity
Antidote: thymidine

Question 6

6-mercaptopurine

Answer 6

MOA: blocks de novo purine synthesis; activated by HGPRTase

Use: leukemia, lymphoma (not CLL or hodgkin’s)

Toxicity: Bone marrow, GI, liver
metabolized by xanthine oxidase, thus increased toxicity with allopurinol

Question 7

Cytarabine

Answer 7

Inhibits DNA polymerase

Use: AML, ALL, high grade non-Hodgkin lymphoma

Adverse: leukopenia, thrombocytopenia, megaloblastic anemia

Question 8

Cyclophosphamide

Isofosfamide

Answer 8

MOA: alkylating agents; covalently link DNA at guanine N-7. Requires activation by liver

Use: non-Hodgkin lymphoma, breast and ovarian cancers

Toxicity: myelosuppression; hemorrhagic cystitis, which can be partially prevented by mesna

Question 9

Nitrosoureas

Answer 9

Carmustine, lomuside, semustine, streptozocin

MOA: alkylate DNA, requires activation
Crosses BBB

Use: brain tumors, including glioblastoma

Toxicity: CNS (dizziness, ataxia)

Question 10

Cisplatin

Carboplatin

Answer 10

Cross-link DNA

Use: testicular, bladder, ovarian and lung carcinomas

Toxicity: Nephrotoxicity and acoustic nerve damage

Question 11

Busulfan

Answer 11

Alkylates DNA

Use: CML. Also used for ablating bone marrow in hematopoietic stem cell transplants

Toxicity: Pulmonary fibrosis, hyperpigmentation

Question 12

Doxorubicin (adraimycin),

Daunorubicin

Answer 12

MOA: generates free radicals and non-covalently intercalate in DNA (creating breaks in DNA strand to decrease replication)

Question 13

Dactinomycin

actinomycin D

Answer 13

Intercalates in DNA

Use: Wilms tumor, Ewing’s sarcoma, rhabdomyosarcoma
childhood tumors

Toxicity: myelosuppression

Question 14

Bleomycin

Answer 14

MOA: induces formation of free radicals, which cause breaks in DNA strands

Use: testicular cancer, Hodgkin’s lymphoma (part of ABVD regimen)

Toxicity: pulmonary fibrosis, skin changes, but minimal myelosuppression

Question 15

Hydroxyurea

Answer 15

MOA: inhibits ribonucleotide reductase: ↓ DNA synthesis (S-phase specific)

Use: melanoma, CML, sickle cell disease (↑ HbF)

Toxicity: bone marrow suppression, GI upset

Question 16

Etoposide

VP-16

Answer 16

MOA: G2 phase specific agent that inhibits topoisomerase II and ↑ DNA degradation

Use: small cell carcinoma of the lung and prostate, testicular carcinoma

Toxicity: myelosuppression, GI irritation, alopecia

Question 17

Prednisone

Answer 17

May trigger apoptosis, even in non-dividing cells

Use: most commonly for glucocorticoid in cancer chemotherapy, CLL, Hodgkin’s lymphomas (part of MOPP regimen), autoimmune diseases

Toxicity: Cushing syndrome, immunosuppression, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis

Question 18

Tamoxifen

Raloxifene

Answer 18

SERMs: receptor antagonists in breast, agonists in bone; block the binding of estrogen to estrogen receptor-positive cells

Use: breast cancer, may be helpful in osteoporosis prevention

Toxicity: ↑ risk endometrial carcinoma via partial agonist effects (tamoxifen only), hot flashes

Question 19

Trastuzumab

herceptin

Answer 19

Monoclonal Ab against HER-2 (erb-B2). Helps kill breast cancer cells that overexpress HER-2, possibly through antibody dependent cytotoxicity

Use: metastatic breast cancer

Toxicity: cardiotoxicity

Question 20

Imatinib

gleevec

Answer 20

Philadelphia chromosome bcr-abl tyrosine kinase inhibitor

Use: CML, GI stromal tumors

Toxicity: fluid retention

Question 21

Vincristine

Vinblastine

Answer 21

MOA: M-phase specific alkaloids that bind to tubulin and block polymerization of microtubules so that mitotic spindle cannot form

Use: part of MOPP regimen (oncovin=vincristine) for Hodgkin’s lymphoma, Wilms’ tumor, choriocarcinoma

Toxicity:
Vincristine: neurotoxicity (areflexia, peripheral neuritis, paralytic ileus)
Vinblastine: bone marrow suppression (BLASTS)

Question 22

Paclitaxel

other -taxols

Answer 22

MOA: M-phase specific agents that bind to tubulin and hyperstabilize polymerized microtubules so that mitotic spindle cannot break down

Use: ovarian and breast cancer

Toxicity: myelosuppression, hypersensitivity