Hem & Onc - Pharm (Individual Cancer Drugs & Common Chemotoxicities) Flashcards
Pg. 405-407 in First Aid 2014 or Pg. 373-375 in First Aid 2013 Sections include: -Cisplastin, carboplatin -Etoposide, teniposide -Irinotecan, topotecan -Hydroxyurea -Prednisone, prednisolone -Tamoxifen, raloxifene -Trastuzumab (Herceptin) -Imatinib (Gleevec) -Rituximab -Vemurafenib -Bevacizumab -Common chemotoxicities
What drug has the same mechanism of Cisplatin? What is their mechanism?
Carboplatin; Cross-link DNA
For what cancers are cisplatin and/or carboplatin used clinically?
(1) Testicular (2) Bladder (3) Ovary (4) Lung (carcinomas)
What are the toxicities associated with Cisplatin/carboplatin?
(1) Nephrotoxicity (2) Acoustic nerve damage
What prevents the nephrotoxicity effect of cisplatin/carboplatin?
Amifostine (free radical scavenger) & chloride diuresis
What drug has the same mechanism as Etoposide? What is their mechanism?
Teniposide; Inhibit topoisomerase II –> decreased DNA degradation; Think: “ eTOPOside inhibits TOPOisomerase II”
For what 3 major cancers are etoposide and/or teniposide used clinically?
(1) Solid tumors (particularly testicular and small cell lung cancer) (2) Leukemias (3) Lymphomas
What are the toxicities associated with etoposide/teniposide?
(1) Myelosuppression (2) GI irritation (3) Alopecia
What is the mechanism of hydroxyurea?
Inhibits nucleotide reductase –> decreased DNA synthesis (S-phase specific)
For what is hydroxyurea used clinically?
(1) Melanoma (2) CML (3) Sickle cell disease (increase HbF)
What are the toxicities associated with hydroxyurea?
(1) Bone marrow suppression (2) GI upset
What is the name of another drug that functions similarly to Prednisone? What is their proposed mechanism?
Prednisolone; May trigger apoptosis, may even work on nondividing cells
For what are prednisone and/or prednisolone used clinically?
(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)
What are the toxicities associated with prednisolone and/or prednisone?
Cushing-like symtoms: weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis
What is a drug that shares the same mechanism as Tamoxifen? What is their mechanism?
Raloxifene; SERMs - receptor antagonists in breast and agonists in bone. Block binding of estrogen to estrogen receptor-positive cells
For what are Tamoxifen and/or Raloxifene used clinically?
(1) Breast cancer treatment (tamoxifen only) and prevention (2) Raloxifene also useful to prevent osteoporosis
What are the toxicities associated with Tamoxifen versus Raloxifene?
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
What is the brand name of Trastuzumab? What is its mechanism?
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
For what is Trastuzumab (Herceptin) used clinically?
HER 2-positive breast cancer and gastric cancer; Think: “her-2 tras2zumab”
What is the toxicity associated with Trastuzumab (Herceptin)?
Cardiotoxicity; Think: “HEARTceptin damages the HEART”
What is the brand name for Imatinib? What is its mechanism?
Gleevec; Tyrosine kinase inhibitor of bcr-abl (Philadelphia chromosome fusion gene in CML) and c-Kit (common in GI stromal tumors)
For what is Imatinib (Gleevec) used clinically?
(1) CML (2) GI stromal tumors
What is the toxicity/side effect associated with Imatinib (Gleevec)?
Fluid retention
What is the mechanism of Rituximab?
Monoclonal antibody against CD20, which is found on most B-cell neoplasms
What are 3 conditions for which Rituximab is clinically used?
(1) Non-Hodgkin’s lymphoma (2) Rheumatoid arthritis (with methotrexate) (3) ITP
What drugs are used in combination for rheumatoid arthritis?
Methotrexate & Rituximab
What is the mechanism of Vemurafenib?
Small molecule inhibitor of forms of B-Raf kinase with V600E mutation
For what is Vemurfenib used clinically?
Metastatic melanoma
What is the mechanism of Bevacizumab?
Monoclonal antibody against VEGF = inhibits angiogenesis
For what is Bevacizumab used clinically?
Solid tumors (colorectal cancer, renal cell carcinoma)
Draw the “chemo-tox man,” labeling common chemotoxicities and the drugs associated with each of them.
See pg. 375 in First Aid for drawing
What drug(s) commonly cause(s) acoustic nerve damage? What other toxicity does/do it/they cause?
Cisplatin/Carboplatin; Nephrotoxicity
What drug(s) commonly cause(s) peripheral neuropathy?
Vincristine
What drug(s) commonly cause(s) pulmonary fibrosis?
Bleomycin & Busulfan
What drug(s) commonly cause(s) cardiotoxicity?
Doxorubicin & Trastuzumab
What drug(s) commonly cause(s) nephrotoxicity? What other toxicity does/do it/they cause?
Cisplatin/Carboplatin; Acoustic nerve damage
What drug(s) commonly cause(s) hemorrhagic cystitis?
Cyclophosphamide
What drug(s) commonly cause(s) myelosuppression?
5-FU, 5-MP, & Methotrexate
What toxicity(-ies) do cisplatin/carboplatin commonly cause?
(1) Acoustic nerve damage (2) Nephrotoxicity
What toxicity(-ies) does vincristine commonly cause?
Peripheral neuropathy
What toxicity(-ies) do bleomycin & busulfan commonly cause?
Pulmonary fibrosis
What toxicity(-ies) do doxorubicin & trastuzumab commonly cause?
Cardiotoxicity
What toxicity(-ies) does cyclophosphamide commonly cause?
Hemorrhagic cystitis
What toxicity(-ies) do 5-FU and 6-MP commonly cause? What other drug commonly causes this as well?
Myelosuppression; Methotrexate
What is the mechanism of Irinotecan? What is another drug that shares this mechanism?
Inhibit topoisomerase I and prevent DNA unwinding and replication
What is the clinical use for Irinotecan?
Colon cancer (irinotecan)
What are 2 clinical uses for Topotecan?
Ovarian and small cell lung cancers (topotecam)
What 2 toxicities are associated with Irinotecan and Topotecan?
(1) Severe myelosuppression (2) Diarrhea
What is the toxicity associated with Rituximab?
Increased risk of progressive multifocal leukoencephalopathy
What toxicity(-ies) is (are) associated with Bevacizumab?
Hemorrhage and impaired wound healing
