Antineoplastics

Question 1

AZA, 6-MP, 6-TG

Answer 1

Mechanism: Purine analog - decrease de novo purine synthesis (blocks PRPP to IMP), activated by HGPRT

Use: Prevent organ rejection, RA, IBD, SLE (to wean patients off steroids in chronic disease or to treat steroid refractory chronic disease)

Toxicity: Myelosupression, GI, liver. DO NOT GIVE AZA or 6-MP w/allopurinol or febuxostat

Question 2

Cladribine (2-CDA)

Answer 2

Mechanism: Purine analog - inhibits DNA polymerase and creates DNA strand breaks

Use: Hairy cell leukemia

Toxicity: Myelosupression, nephrotoxicity, neurotoxicity

Question 3

Cytarabine (arabinofuranosyl cytidine)

Answer 3

Mechanism: Pyrimidine analog - inhibits DNA polymerase

Use: AML, lymphomas

Toxicity: CYTarabine causes panCYTopenia (anemia is megaloblastic)

Question 4

5-FU

Answer 4

Mechanism: Pyrimidine analog - 5-FU–>5F-dUMP –> complexes covalently w/folic acid –> INHIBITS THYMIDLATE SYNTHASE –> decreased dTMP therefore decreased DNA synthesis

Use: Colon cancer, pancreatic cancer, basal cell carcinoma (topical)

Toxicity: Myelosupression not reversible with leuocovorin (folinic acid)

Question 5

MTX

Answer 5

Mechanism: Folic acid analog COMPETITIVELY INHIBITS DHF REDUCTASE –> decreased dTMP therefore decreased DNA synthesis

Use: ALL, lymphomas, choriocarcinoma, sarcomas; ectopic pregnancy, medical abortion with mosoprostol, RA, psoriasis, IBD, vasculitis

Toxicity: Myelosupression, reversible with leucovorin, hepatotoxic, mucositis, pulmonary fibrosis

Question 6

Bleomycin

Answer 6

Mechanism: Free radical formation –> breaks in DNA strands

Use: Testicular cancer, Hodgkin lymphoma

Toxicity: Pulmonary fibrosis, skin hyperpigmentation, mucositis. Minimal myelosupression :)

Question 7

Dactinomycin (ACTinomycin D)

Answer 7

Mechanism: Intercalates in DNA

Use: Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. (Childhood tumors – children ACT out)

Toxicity: Myelosupresion

Question 8

Doxorubicin, daunorubicin

Answer 8

Mechanism: Free radicals –> intercalate in DNA –> DNA breaks

Use: Solid tumors, leukemias, lymphomas

Toxicity: Dilated cardiomyopathy (prevent with Dexrazoxane), myelosupression, alopecia.

Question 9

Busulfan

Answer 9

Mechanism: Cross-links DNA

Use: CML. Ablate bone marrow before bone marrow transplant

Toxicity: Pulmonary fibrosis, severe myelosupression, hyperpigmentation

Question 10

Cyclophosphamide, ifosfamide

Answer 10

Mechanism: Cross-link DNA at guanine N-7. REQUIRES BIOACTIVATION BY LIVER

Use: Solid tumors, leukemia, lymphomas

Toxicity: Hemorrhagic cystitis (prevent with mesna). Myelosupression.

Question 11

Nitrosoureas (carmustine, lomustine, semustine, streptozocin)

Answer 11

Mechanism: Crosses BBB, cross-links DNA

Use: Brain tumors (including glioblastoma multiforme)

Toxicity: CNS toxicity (convulsions, dizziness, ataxia)

Question 12

Paclitaxel, other taxols

Answer 12

Mechanism: Hyperstabalize microtubules in M phase (anaphase cannot occur) “Taxing to stay polymerized”

Use: Ovarian and breast carcinomas

Toxicity: Myelosupression, alopecia, hypersensitivity

Question 13

Vincristine, vinblastine

Answer 13

Mechanism: Vinca alkaloids that bind B-tubulin and inhibit polymerization (M-phase arrest)

Use: Solid tumors, leukemias, Hodgkin (vinblastine), non-Hodgkin (vincristine)

Toxicity: Vincristine – neurotoxcitiy (areflexia, paralytic ileus, peripheral neuritis). Vinblastine blasts bone marrow.

Question 14

Cisplatin, carboplatin

Answer 14

Mechanism: Cross-link DNA

Use: Testicular, bladder, ovary, and lung carcinomas

Toxicity: Nephrotxicity (prevent with amifostine and saline diuresis), ototoxicity

Question 15

Etoposide, teniposide

Answer 15

Mechanism: Inhibits topoisomerase II

Use: Solid tumors (esp testicular and small cell lung cancer), leukemia, lymphomas

Toxicity: Myelosupressoin, GI upset, alopecia

Question 16

Irinotecan, topotecan

Answer 16

Mechanism: Inhibits topisomerase I

Use: Colon cancer (irnotecan); ovarian and small cell lung cancers (toptecan)

Toxicity: Severe myelosupression, diarrhea

Question 17

Hydroxyurea

Answer 17

Mechanism: Inhibits ribonucleotide reductase (S-phase specific)

Use: Melanoma, CML, sick cell disease (HbF)

Toxicity: Severe myelosupression, GI upset

Question 18

Prednisone, prednisolone

Answer 18

Mechanism: Binds intracytoplasmic receptor to alter gene transcription

Use: CLL, non-Hodgkin lymphoma

Toxicity: Cushing, wieght gain, obesity, muscle breakdown, osteoporosis, htn, peptic ulcers, psychosis

Question 19

Bevacizumab

Answer 19

Mechanism: Monoclonal ab against VEGF

Use: Solid tumors (colorectal, renal cell carcinoma)

Toxicity: Hemorrhage, blood clots, impaired wound healing

Question 20

Erlotinib

Answer 20

Mechanism: EGFR tyrosin kinase inhibitor

Use: Non-small cell lung carcinoma

Toxicity: Rash

Question 21

Imatinib

Answer 21

Mechanism: Tyrosine kinase inhibitor of BCR-ABL (CML) and c-kit

Use: CML, GI stromal tumors

Toxicity: Fluid retention

Question 22

Rituximab

Answer 22

Mechanism: Ab against CD20

Use: Non-Hodgkin lymphoma, CLL, IBD, RA

Toxicity: Risk of PML

Question 23

Tamoxifen, raloxifene

Answer 23

Mechanism: Selective estrogen receptor modulator (SERMs) - receptor antagonist in breast and agonists in bone. Blocks finding of estrogen to ER + cells

Use: Breast cancer (tamoxifen only) and prevention. Raloxifene used to prevent osteoporosis

Toxicity: Tamoxifen - partial agonist in endometrium, which increases risk of endometrial cancer; “hot flashes”. Raloxifene - no increase in endometrial carcinoma because it is an estrogen receptor antagonist in endometrial tissue

Question 24

Trastuzumab (Herceptin)

Answer 24

Mechanism: Monoclonal ab against HER-2 (c-erbB2), a tryosine-kinase receptor

Use: HER-2 + breast cancer and gastric cancer (tras2zumab)

Toxicity: Heart

Question 25

Vemurafenib

Answer 25

Mechanism: Small molecule inhibitor of BRAF oncogene + melanoma

Use: Metastatic melanoma