Classic Antineoplastics

Question 1

Methotrexate

Answer 1

Purine synthesis inhibitor (Antimetabolite)

Folic acid antagonist

Inhibits DHFR and one-carbon transfers required for de novo purine ring synthesis and dTMP synthesis for dUMP

Toxicities: Classical toxicities, renal and liver toxicity

Question 2

9-Mercaptopurine

Thioguanine

Answer 2

Purine synthesis inhibitors (purine analogue)

Inhibit purine ring synthesis and interconversion of purines. Incorporated into DNA, when phosphorylated disrupts structure and function, genetic defect in metabolism of 6-MP

Classical toxicities

Question 3

Fluorouracil

Answer 3

Pyrimidine synthesis inhibitor (Pyrimidine analogue)

Blocks dTMP formation from dUMP by inhibiting thymidylate synthetase, augmented by leukovorin

Classical toxicities: choleostatic jaundice

Question 4

Cytarabine

Answer 4

DNA polymerase inhibitor

Completely inhibits incorporation of dCTP into DNA

Classical toxicities neurotoxicity, cholestatic jaundice

Question 5

Nitrogen mustards 
Cyclophosphamide 
Nitrosoureas
Busulfan 
Dacarbazine

Answer 5

Inhibitors or DNA function by direct interactions

React covalently with DNA as alkylating agents, most crosslink DNA strands (Nitrosoureas and busulfan enter the CNS)

Classical toxicities, mutagenic, carcinogenic, secondary leukemias, cyclophos, hemorrhagic cystitis

Question 6

Cis-platinol carboplatin

Answer 6

Inhibitor of DNA function

Cross-link DNA

Toxicities: Ototoxicity, nephrotoxicity, neuropathy, myelosuppression

Question 7

Dactinomycin (actinomycin D)

Deoxyguanine base specific

Answer 7

Inhibitor of DNA function

Intercalate between base pairs and inhibit nucleic acid synthesis, generate free radicals that break DNA strands

Classical toxicities, possible mutagenesis

Question 8

Adriamycin (Doxorubicin)

Answer 8

Inhibitor of DNA function

Intercalate between base pairs and inhibit nucleic acid synthesis, generate free radicals that break DNA strands

Noted for cardiotoxicity

Question 9

Bleomycin

Answer 9

Inhibitors of DNA function

Used to treat Hodgkin lymphoma

Intercalate between base pairs and inhibit nucleic acid synthesis, generate free radicals that break DNA strands

Toxicities: toxicity in skin and lungs (not bone marrow)

Question 10

Etoposide

Teniposide

Irintocan

Answer 10

Inhibitors of DNA function

DNA gyrase and topoisomerase inhibitors causing ds breaks

Toxicities: mutagenic with possible secondary induced leukemias

Question 11

Retinoic acid and retinoids

Answer 11

Vitamins

After transcription to trigger genetic programs allowing for differentiation of tumor cells

Question 12

Estrogens

Androgens

Antiandrogens

SERMs

GnRH agonists and antagonist

Aromatase inhibitors

Answer 12

Estradiol, Danazol

Flutamnide

Tamoxifen, raloxifen

Leuprolide

Dagarelix, cetrorelix

Anastrozole, lentrozole, vorozole, examestane

Question 13

Vincristine (Vinblastine)

Answer 13

Mitotic spindle inhibitors

Bind to tubulin to disrupt microtubules, producing metaphase arrest

Toxicities: Neurotoxicity, none marrow hypoplasia

Question 14

Taxol (Docetaxel)

Answer 14

Mitotic spindle inhibitors

Bind to tubulin to stabilize microtubules, producing metaphase arrest.

Toxicities: myelosuppression, neurotoxicity

Question 15

Hydroxyurea

Answer 15

Ribonucleotide reductase inhibitor

Depletes deoxyribonucleoside triphosphate arresting cells in S phase; used in CML and AML

Question 16

Asparaginase

Answer 16

Arrest protein synthesis in tumor cells

Hydrolyzes exogenous asparagine inhibiting ALL tumor cells that are unable to synthesize asparagine while normal cells retain this capacity.

Question 17

Cyclophosphamide ( A nitrogen mustard)

Answer 17

Used to treat many solid and heme malignancies

Is a prodrug activated by cytochrome p450

A nitrogen mustard that works as an alkylating agent

Toxicities: Hemorrhagic cystitis