Other antineoplastic agents

Question 1

Cisplatin, carboplatin

Answer 1

Mechanism: Cross-link DNA.

Clinical use: Testicular, bladder, ovary, and lung carcinomas.

Toxicity: Nephrotoxicity and acoustic nerve damage. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis.

Question 2

Etoposide, teniposide

Answer 2

Mechanism: Inhibit topoisomerase II -> Increased DNA degradation.

Clinical use: Solid tumors, leukemias, lymphomas.

Toxicity: Myelosuppression, GI irritation, alopecia.

Question 3

Hydroxyurea

Answer 3

Mechanism: Inhibits ribonucleotide reductase
-> Decreased DNA Synthesis (S-phase specific).

Clinical use: Melanoma, CML, sickle cell disease (Increased HbF).

Toxicity: Bone marrow suppression, GI upset.

Question 4

Prednisone, prednisolone

Answer 4

Mechanism: May trigger apoptosis. May even work on non dividing cells.

Clinical use: Most commonly used glucocorticoid in cancer chemotherapy. Used in CLL, non-Hodgkin’s lymphomas (part of combination chemotherapy regimen). Also used as an immunosuppressant (e.g. autoimmune diseases).

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

Question 5

Tamoxifen, raloxifene

Answer 5

Mechanism: SERMs-receptor antagonists in breast and agonists in bone. Block the binding of estrogen to estrogen receptor-positive cells.

Clinical use: Breast cancer treatment and prevention. Also useful to prevent osteoporosis.

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

Question 6

Trastuzumab (Herceptin)

Answer 6

Mechanism: Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase. Helps kill breast cancer cells that over express HER-2, possibly through antibody-dependent cytotoxicity.

Clinical use: HER-2-positive breast cancer.

Toxicity: Cardiotoxicity.

Question 7

Imatinib (Gleevec)

Answer 7

Mechanism: Philadelphia chromosome bcr-abl tyrosine kinase inhibitor.

Clinical use: GML, GI stromal tumors.

Toxicity: Fluid retention.

Question 8

Rituximab

Answer 8

Mechanism: Monoclonal antibody against CD20, which is found on most B-cell neoplasms.

Clinical use: Non-Hodgkin’s lymphoma, rheumatoid arthritis (with methotrexate).

Toxicity:

Question 9

Vemurafenib

Answer 9

Mechanism: Small molecule inhibitor of forms of the B-Raf kinase with the V600E mutation.

Clinical use: Metastatic melanoma.

Toxicity:

Question 10

Bevacizumab

Answer 10

Mechanism: Monoclonal antibody against VEGF. Inhibits angiogenesis.

Clinical use: Solid tumors.

Toxicity: