Tox: Marrow, allergies, myalgia, arthralgia, neurologic, skin (thin fragile nails
What are the properties of podophyllotoxins?
Emetic, cathartic, antihelminthic.
Inhibit DNA topoisomerase 2 thus inhibiting DNA and RNA synthesis- cell cycle specific
Works in testicular cancer, small cell lung cancer, NHL, and some others
What are the properties of camptothecins?
Inhibit topoisomerase 1 blocking DNA synth and killing the cell
Irinotecan used in metastatic colon cancer- causes excessive diarrhea, also has cholinergic effect requiring atropine
Topotecan- used mostly in small cell lung and ovarian cancer- causes myelosuppression
What are the properties of the miscellaneous anti cancer agents?
Cisplatinum, Carboplatinum, and Oxaliplatinum
Can mould shape
Act as alkylators
cisplatinum has nephrotoxicity
carboplatinum causes myelosuppression
Oxaliplatinum causes cold intolerance
What is cisplatinum?
Platinum complex with 2 Cl- and 2 H3N groups
Curative for most germ cell tumors
Works well for lung, breast, and unknown primary cancers
Carboplatinum has the same spectrum but less nephro tox
Oxaliplatinum has unique activity in colon cancer
How do you prevent nephro and neuro toxicity from platinum use?
Nephrotoxicity: parenteral and oral hydration
Use mannitol(volume expander) to force diuresis
Replace K+ and magnesium
Use Amifostine- a compound that picks up cisplatin metabolites from the tissues
Neurotoxicity: Ca and magnesium infusions are somewhat protective
Cold induced neuropathy prevented by avoidance of cold things.
What is L- Asparaginase?
Anti cancer drug from pig serum that inhibit leukemia cells by hydrolyzing circulating asparagine- this inhibits tumor growth because most tumors have low asparagine synthetase activity. So protein synthesis is inhibited.
What are the major classes of anti hormonal therapy?
Anti Estrogenic- Tamoxifen, aromatase inhibitors, progestins, and LHRH analogues
Anti Androgenic- Receptor block (flutamide/biclutamide) LHRH analogues
What are the properties of Tamoxifen?
Blocks the estrogen receptor- given orally
Tox: Thromboembolic disease
Faslodex is an irreversible blocker of the ER
What is Aminogluthemide?
An aromatase inhibitor that is very toxic and requires steroid use at same time
What are the third gen aromatase inhibitors?
Anastrozole, Letrozole, and Exemestane
Tox is caused by estrogen withdraw- osteoporosis, hot flashes, and arthralgia.
Aromatase inhibitors more active in post menopausal than tamoxifen
When does tamoxifen work best?
Post menopausal because ER is up reg to combat low estrogen levels
Has an anti estrogen effect on the breast but estrogen effect in the uterus
Aromatase inhibitors only used in post menopausal when adrenal is making the estrogen
What is the toxicity of flutamide and biclutamide?
hot flashes, impotence, and andropause
What is the purpose of LHRH analogues?
Leuprolide and goserelin- work by decreasing pituitary release of LH and FSH leading to decreased estrogen and testosterone prod
Work for prostate and breast cancers
Cause flare effect and impotence
What are the properties of corticosteroid therapy in cancer?
Cause malignant lymphocytes to lyse.
Work in Hodgkin's and NHL
Also used in supportive care as anti nauseant, appetite stimulant, reduction of cerebral edema, and analgesic