Cancer Drugs

Question 1

Cisplatin, carboplatin

Answer 1

MOA: Cross-link DNA

Use: Testicular, bladder, ovary, & lung carcinomas

Toxicity: Nephrotoxicity & acoustic nerve damage
*Prevent nephrotoxicity w/ amifostine (free radical scavenger) & chloride diuresis

Question 2

Hydroxyurea

Answer 2

MOA: Inhibits ribonucleotide reductase –> Decreased DNA synthesis (S phase specific)

Use: Melanoma, CML, sickle cell disease (Increases HbF)

Toxicity: Bone marrow suppression, GI upset

Question 3

Prednisone

Answer 3

MOA: May trigger apoptosis; may work on nondividing cells

Use: Most commonly used glucocorticoid in cancer chemotherapy. CLL, Hodkin’s lymphomas. Also used as immunosuppressant in autoimmune disease

Toxicity: Cushing-like symptoms, immunosuppression, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis

Question 4

Tamoxifen, raloxifene

Answer 4

MOA: SERM receptor antagonist in breast & agonist in bone; block estrogen binding to estrogen-receptor positive cells

Use: Breast cancer; prevent osteoporosis

Toxicity: Tamoxifen increases risk of endometrial carcinoma via partial agonist effects; hot flashes
Raloxifene doesn’t increase risk of endometrial cancer b/c its an endometrial antagonist

Question 5

Trastuzumab (Herceptin)

Answer 5

MOA: Monoclonal antibody against HER-2 (erb-B2), a tyrosine kinase

Use: Metastatic breast cancer

Toxicity: Cardiotoxicity

Question 6

Imatinib (Gleevac)

Answer 6

MOA: Philadelphia chromosome bcr-abl tyrosine kinase inhibitor

Use: CML, GI stromal tumors

Toxicity: Fluid retention

Question 7

Rituximab

Answer 7

MOA: Monoclonal antibody against CD20 (found on B cell neoplasms)

Use: Non-Hodgkin’s lymphoma, RA (combine w/ methotrexate)

Question 8

Methotrexate

Answer 8

MOA: Anti-metabolite, folic acid analog that inhibits dihydrofolate reductase ultimately decreasing DNA & protein synthesis

Use: Leukemias, lymphomas, choriocarcinoma, sarcomas; abortion, ectopic pregnancy, RA, psoriasis

Toxicity: Myelosuppression (reverse w/ leucovorin- folinic acid); macrovesicular fatty change in liver; mucositis; teratogenic

Question 9

5-FU

Answer 9

MOA: Anti-metabolite; pyrimidine analog; inhibits thymidylate synthase & ultimately decreases DNA & protein synthesis

Use: Colon cancer, solid tumors, basal cell carcinoma (topical)
Synergy w/ methotrexate

Toxicity: Myelosuppression (treat OD w/ thymidine); photosensitivity

Question 10

6-MP

Answer 10

MOA: Anti-metabolite; purine analog; decreases de novo purine synthesis; activated by HGPRTase

Use: Leukemia, lymphoma (NOT CLL or Hodgkin’s)

Toxicity: Bone marrow, GI, liver
Metabolized by xanthine oxidase :. toxicity increases w/ allopurinol

Question 11

6-TG

Answer 11

MOA: Anti-metabolite; similar to 6MP

BUT treats ALL and can be given w/ allopurinol

Question 12

Cytarabine

Answer 12

MOA: Anti-metabolite; pyrimidine analog; inhibits DNA polymerase

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

Toxicity: Leukopenia, thrombocytoenia, megaloblastic anemia

Question 13

Cladribine

Answer 13

MOA: Antimetabolite, purine analog resistant to degradation by adenosine deaminiase

Use: Hairy Cell Leukemia

Question 14

Dactinomycin

Answer 14

MOA: Antitumor antibiotic; intercalates in DNA

Use: Wilms tumor, Ewing’s sarcoma, rhabdomyosarcoma; used for children’s tumors

Toxicity: myelosuppression

Question 15

Doxorubicin/ danorubicin

Answer 15

MOA: Antitumor antibiotic; Generate free radicals; Noncovalently intercalage in DNA –> breaks in DNA –> decreased replication

Use: Hodgkin’s lymphoma; myeloma, sarcoma, solid tumors (breast, ovary, lung)

Toxicity: Cardiotoxicity (prevent w/ dexrazoxane, an iron chelating agent); myelosuppression, alopecia

Question 16

Bleomycin

Answer 16

MOA: Antitumor antibiotic; induces free radical formation, causing breaks in DNA strands

Use: Testicular cancer, hodgkind’s lymphoma

Toxicity: pulmonary fibrosis, skin changes, minimal myelosuppression

Question 17

Etoposide (VP-16), teniposide

Answer 17

MOA: Antitumor antibiotic; inhibits topoisomerase II leading to increased DNA degradation

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

Toxicity: Myelosuppression, GI irritation, alopecia

Question 18

Cyclophosphamide, ifosfamide

Answer 18

MOA: Alkylating agent, covalently X-links DNA @ guanine N-7. Requires bioactivation by liver

Use: Non-Hodgkin’s lymphoma, breast & ovarian carcinomas; immunosuppressant

Toxicity: Myelosuppression; hemorrhagic cystitis (partially prevent w/ mesna to bind toxic metabolite, acrolein)

Question 19

Nitrosureas (carmustine, lomustine, semustine, streptozocin)

Answer 19

MOA: Alkylating agent, requires bioactivation; crosses BBB

Use: Brain tumors (including glioblastoma multiforme)

Toxicity: CNS toxicity (dizziness, ataxia)

Question 20

Busulfan

Answer 20

MOA: Alkylating agent; alkylates DNA

Use: CML; used to ablate patient’s bone marrow before bone marrow transplant

Toxicity: Pulmonary fibrosis, hyperpigmentation

Question 21

Vincristine, vinblastine

Answer 21

MOA: Microtubule inhibitor; alkaloids that bind to tubulin in M-phase & block polymerization of microtubules so that mitotic spindle cannot form

Use: Hodgkin’s lymphoma; Wilm’s tumor; choriocarcinoma; ALL

Toxicity: Vincristine causes neurotoxicity (areflexia, peripheral neuritis), paralytic ileus
Vinblastine blasts bone marrow

Question 22

Paclitaxel

Answer 22

MOA: Microtubule inhibitor; hyperstabilize polymerized microtubules in M-phase so mitotic spindle can’t break down (no anaphase)

Use: ovarian & breast carcinoma

Toxicity: Myelosuppression & hypersensitivity