Hem & Onc - Pharm (Individual Cancer Drugs & Common Chemotoxicities)

Question 1

What drug has the same mechanism of Cisplatin? What is their mechanism?

Answer 1

Carboplatin; Cross-link DNA

Question 2

For what cancers are cisplatin and/or carboplatin used clinically?

Answer 2

(1) Testicular (2) Bladder (3) Ovary (4) Lung (carcinomas)

Question 3

What are the toxicities associated with Cisplatin/carboplatin?

Answer 3

(1) Nephrotoxicity (2) Acoustic nerve damage

Question 4

What prevents the nephrotoxicity effect of cisplatin/carboplatin?

Answer 4

Amifostine (free radical scavenger) & chloride diuresis

Question 5

What drug has the same mechanism as Etoposide? What is their mechanism?

Answer 5

Teniposide; Inhibit topoisomerase II –> decreased DNA degradation; Think: “ eTOPOside inhibits TOPOisomerase II”

Question 6

For what 3 major cancers are etoposide and/or teniposide used clinically?

Answer 6

(1) Solid tumors (particularly testicular and small cell lung cancer) (2) Leukemias (3) Lymphomas

Question 7

What are the toxicities associated with etoposide/teniposide?

Answer 7

(1) Myelosuppression (2) GI irritation (3) Alopecia

Question 8

What is the mechanism of hydroxyurea?

Answer 8

Inhibits nucleotide reductase –> decreased DNA synthesis (S-phase specific)

Question 9

For what is hydroxyurea used clinically?

Answer 9

(1) Melanoma (2) CML (3) Sickle cell disease (increase HbF)

Question 10

What are the toxicities associated with hydroxyurea?

Answer 10

(1) Bone marrow suppression (2) GI upset

Question 11

What is the name of another drug that functions similarly to Prednisone? What is their proposed mechanism?

Answer 11

Prednisolone; May trigger apoptosis, may even work on nondividing cells

Question 12

For what are prednisone and/or prednisolone used clinically?

Answer 12

(1) Most commonly used glucocorticoid in cancer chemotherapy - Used in CLL, non-Hodgkin’s lymphomas (part of combination chemotherapy regimen) (2) Immunosuppressant (e.g., autoimmune diseases)

Question 13

What are the toxicities associated with prednisolone and/or prednisone?

Answer 13

Cushing-like symtoms: weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis

Question 14

What is a drug that shares the same mechanism as Tamoxifen? What is their mechanism?

Answer 14

Raloxifene; SERMs - receptor antagonists in breast and agonists in bone. Block binding of estrogen to estrogen receptor-positive cells

Question 15

For what are Tamoxifen and/or Raloxifene used clinically?

Answer 15

(1) Breast cancer treatment (tamoxifen only) and prevention (2) Raloxifene also useful to prevent osteoporosis

Question 16

What are the toxicities associated with Tamoxifen versus Raloxifene?

Answer 16

TAMOXIFEN - partial agonist in endometrium, which increases risk of endometrial cancer; “hot flashes”; RALOXIFENE - no increase in endometrial carcinoma because it is an endometrial antagonist

Question 17

What is the brand name of Trastuzumab? What is its mechanism?

Answer 17

Herceptin; Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase. Helps kill breast cancer cells that overexpress HER-2, through inhibition of HER2-initiated cellular signaling and antibody-dependent cytotoxicity

Question 18

For what is Trastuzumab (Herceptin) used clinically?

Answer 18

HER 2-positive breast cancer and gastric cancer; Think: “her-2 tras2zumab”

Question 19

What is the toxicity associated with Trastuzumab (Herceptin)?

Answer 19

Cardiotoxicity; Think: “HEARTceptin damages the HEART”

Question 20

What is the brand name for Imatinib? What is its mechanism?

Answer 20

Gleevec; Tyrosine kinase inhibitor of bcr-abl (Philadelphia chromosome fusion gene in CML) and c-Kit (common in GI stromal tumors)

Question 21

For what is Imatinib (Gleevec) used clinically?

Answer 21

(1) CML (2) GI stromal tumors

Question 22

What is the toxicity/side effect associated with Imatinib (Gleevec)?

Answer 22

Fluid retention

Question 23

What is the mechanism of Rituximab?

Answer 23

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

Question 24

What are 3 conditions for which Rituximab is clinically used?

Answer 24

(1) Non-Hodgkin’s lymphoma (2) Rheumatoid arthritis (with methotrexate) (3) ITP

Question 25

What drugs are used in combination for rheumatoid arthritis?

Answer 25

Methotrexate & Rituximab

Question 26

What is the mechanism of Vemurafenib?

Answer 26

Small molecule inhibitor of forms of B-Raf kinase with V600E mutation

Question 27

For what is Vemurfenib used clinically?

Answer 27

Metastatic melanoma

Question 28

What is the mechanism of Bevacizumab?

Answer 28

Monoclonal antibody against VEGF = inhibits angiogenesis

Question 29

For what is Bevacizumab used clinically?

Answer 29

Solid tumors (colorectal cancer, renal cell carcinoma)

Question 30

Draw the "chemo-tox man," labeling common chemotoxicities and the drugs associated with each of them.

Answer 30

See pg. 375 in First Aid for drawing

Question 31

What drug(s) commonly cause(s) acoustic nerve damage? What other toxicity does/do it/they cause?

Answer 31

Cisplatin/Carboplatin; Nephrotoxicity

Question 32

What drug(s) commonly cause(s) peripheral neuropathy?

Answer 32

Vincristine

Question 33

What drug(s) commonly cause(s) pulmonary fibrosis?

Answer 33

Bleomycin & Busulfan

Question 34

What drug(s) commonly cause(s) cardiotoxicity?

Answer 34

Doxorubicin & Trastuzumab

Question 35

What drug(s) commonly cause(s) nephrotoxicity? What other toxicity does/do it/they cause?

Answer 35

Cisplatin/Carboplatin; Acoustic nerve damage

Question 36

What drug(s) commonly cause(s) hemorrhagic cystitis?

Answer 36

Cyclophosphamide

Question 37

What drug(s) commonly cause(s) myelosuppression?

Answer 37

5-FU, 5-MP, & Methotrexate

Question 38

What toxicity(-ies) do cisplatin/carboplatin commonly cause?

Answer 38

(1) Acoustic nerve damage (2) Nephrotoxicity

Question 39

What toxicity(-ies) does vincristine commonly cause?

Answer 39

Peripheral neuropathy

Question 40

What toxicity(-ies) do bleomycin & busulfan commonly cause?

Answer 40

Pulmonary fibrosis

Question 41

What toxicity(-ies) do doxorubicin & trastuzumab commonly cause?

Answer 41

Cardiotoxicity

Question 42

What toxicity(-ies) does cyclophosphamide commonly cause?

Answer 42

Hemorrhagic cystitis

Question 43

What toxicity(-ies) do 5-FU and 6-MP commonly cause? What other drug commonly causes this as well?

Answer 43

Myelosuppression; Methotrexate

Question 44

What is the mechanism of Irinotecan? What is another drug that shares this mechanism?

Answer 44

Inhibit topoisomerase I and prevent DNA unwinding and replication

Question 45

What is the clinical use for Irinotecan?

Answer 45

Colon cancer (irinotecan)

Question 46

What are 2 clinical uses for Topotecan?

Answer 46

Ovarian and small cell lung cancers (topotecam)

Question 47

What 2 toxicities are associated with Irinotecan and Topotecan?

Answer 47

(1) Severe myelosuppression (2) Diarrhea

Question 48

What is the toxicity associated with Rituximab?

Answer 48

Increased risk of progressive multifocal leukoencephalopathy

Question 49

What toxicity(-ies) is (are) associated with Bevacizumab?

Answer 49

Hemorrhage and impaired wound healing