Chemotherapy Exam Review

A comprehensive guide to chemotherapy—covering mechanisms of action, contraindications, drug interactions, adverse effects, and treatment guidelines for various chemotherapy agents.

What is the MOA of doxorubicin (adriamycin)?

Cytotoxic anthracycline antibiotic – binds to nucleic acids to inhibit nucleotide replication and action of DNA and RNA polymerases leading to apoptosis.

What are the CIs of doxorubicin (adriamycin)?

Neutrophil count <1500, severe hepatic impairment, recent MI, myocardial insufficiency, severe arrhythmia, prior complete cumulative doses of doxorubicin, daunorubicin, idarubicin and/or other anthracyclines, and anthracenediones.

What are the warnings of doxorubicin (adriamycin)?

Cardiotoxicity, secondary AML or myelodysplastic syndrome, reduce dose in severe hepatic dysfunction, severe myelosuppression, and extravasation.

What are the DDIs of doxorubicin (adriamycin)?

Cyclosporine, paclitaxel, and streptozocin increase DOX concentration.

What is the MOA of cyclophosphamide (cytoxan)?

Pro-drug converted to an alkylating agent related to nitrogen mustards; interferes with growth of rapidly proliferating malignant cells.

What are the CIs of cyclophosphamide (cytoxan)?

Urinary outflow obstruction.

What are the warnings of cyclophosphamide (cytoxan)?

Cardiotoxicity, urinary tract/renal toxicity, myelosuppression/immunosuppression.

What is the pregnancy category in cyclophosphamide (cytoxan) use?

Category D; avoid in lactation.

What is the pregnancy category in doxorubicin (Adriamycin) use?

Pregnancy category D; avoid lactation.

What are the ADRs of cyclophosphamide (cytoxan)?

Neutropenia, fever, alopecia, nausea/vomiting/diarrhea.

What are the DDIs of cyclophosphamide (cytoxan)?

ACE inhibitors, thiazides, and paclitaxel.

What is the MOA of paclitaxel (taxol)?

Inhibits normal dynamic reorganization of microtubule network essential for interphase and mitotic cellular functions.

What are the CIs of paclitaxel (taxol)?

Neutrophils <1500, AIDs-related Kaposi’s sarcoma with neutrophils <1000.

What are the warnings of paclitaxel (taxol)?

Anaphylaxis/severe hypersensitivity (2-4%), bone marrow suppression, cardiac conduction abnormalities, hepatic impairment.

What is the pregnancy category in paclitaxel (taxol) use?

Pregnancy category C; avoid lactation.

What are the ADRs of paclitaxel (taxol)?

Peripheral neuropathy, neutropenia, arthralgia, myalgias, nausea/vomiting/diarrhea, mucositis.

What are the DDIs of paclitaxel (taxol)?

CYP2C8 and CYP3A4 inducers and inhibitors; taxol increases doxorubicin concentration x2.

What is the MOA of fluorouracil (5FU)?

Nucleoside metabolic inhibitor which interferes with synthesis of DNA and (lesser extent) RNA in rapidly growing cells, leading to cell death.

What are the indications for fluorouracil (5FU) use?

Adenocarcinoma of the breast, colon/rectum, gastric, pancreas.

What are the CIs of fluorouracil (5FU)?

None really, but increased risk of fatal ADRs with low or absent dipyrimidine dehydrogenase.

What are the warnings of fluorouracil (5FU)?

Cardiotoxicity, neurologic toxicity, myelosuppression.

What are the ADRs of fluorouracil (5FU)?

Pancytopenia, GI ulceration, nausea/vomiting, photosensitivity, epistaxis, thrombophlebitis, nystagmus, headache.

What is the MOA of aromatase inhibitors?

Blocks conversion of androgens to estrogens via aromatase enzyme, decreasing endogenous estrogen by 95%.

When are aromatase inhibitors indicated?

Adjuvant endocrine therapy in postmenopausal but not premenopausal women for breast cancer.

What is the MOA of anastrozole?

Nonsteroidal, reversibly binds to the aromatase enzyme.

What is the dosing for non-steroidal aromatase inhibitors?

1 mg tablet daily with or without food.

What is the treatment duration of non-steroidal aromatase inhibitors in those with advanced breast cancer?

Until tumor progression.

What is the treatment duration of non-steroidal aromatase inhibitors in postmenopausal women receiving adjuvant treatment with early breast cancer?

Optimal duration unknown; administered for 5 years in some trials.

What is anastrozole used for 1st line?

Treatment of postmenopausal women with hormone receptor-positive or receptor unknown locally advanced or metastatic breast cancer.

What is anastrozole used for in general?

Treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy.

What is the MOA of letrozole?

Nonsteroidal; reversibly binds to aromatase enzyme.

What is letrozole used for 1st line?

Treatment of postmenopausal women with hormone receptor-positive or unknown locally advanced or metastatic breast cancer.

What is letrozole used for in general?

Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer OR advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy.

What extended treatment is letrozole used for?

Extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy.

What is the MOA of exemestane?

Irreversible inhibitor, steroidal inhibitor that is a derivative of androstenedione.

What is exemestane used for?

Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy OR postmenopausal women with early breast cancer treated with 2-3 years of tamoxifen.

What are the CIs of exemestane?

Premenopausal women, pregnancy, allergy.

What are the warnings of exemestane?

Increased cardiovascular events, decreased bone density, increased cholesterol.

What are the ADRs of exemestane?

Hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression.

What are the DDIs of exemestane?

Strong CYP3A4 inducers and inhibitors; should not be used with tamoxifen, and estrogens.

What are the indications for raloxifene?

Treatment and prevention of osteoporosis in postmenopausal women.

What is the dosing of raloxifene?

60 mg PO daily.

What are the CIs of raloxifene?

Active or past history of VTE, pregnancy, or exogenous estrogen.

What are the warnings of raloxifene?

DVT/PE, increased risk of stroke, liver disease, pre-menopause, increased triglycerides.

What are the ADRs of raloxifene?

Hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, sweating.

What are the DDIs of raloxifene?

Cholestyramine decreases absorption, warfarin.

What is the MOA of tamoxifen, toremifene?

Antitumor effect in breast cancer believed due to anti-estrogenic effects blocking the growth-stimulating action of estrogen in tumors.

What does tamoxifen, toremifene treat?

Adjuvant treatment of breast cancer/ductal carcinoma in situ OR of metastatic breast cancer in women and men.

What does toremifene treat?

Metastatic breast cancer in postmenopausal women with E2-receptor (ER+) or unknown tumors.

What is the dosing of tamoxifen?

20-40 mg PO daily.

What is the dosing of toremifene?

60 mg PO daily.

What is the dosing of fulvestrant?

After loading dose(s), 500 mg IM per month (decrease dose in liver disease).

What are the CIs of estrogen agonist/antagonists?

Allergy, pregnancy, avoid in breastfeeding.

What is a specific CI of tamoxifen?

History of DVT/PE or anticoagulation indication.

What are the specific warnings of fulvestrant?

Bleeding, decreased platelets, injection site reactions.

What are the specific warnings of toremifene?

QT interval prolongation.

What are the ADRs of estrogen agonist/antagonists?

Nausea/vomiting, anorexia, asthenia, bone and muscle pain, arthralgia, headache, back pain, hot flashes, increased LFTs.

What are the specific DDIs of toremifene?

Avoid strong CYP3A4 inhibitors, inducers, drugs that increase QT interval risk.

What are the CIs of leuprolide?

Hypersensitivity.

What is the pregnancy category of leuprolide?

Category X; avoid lactation.

What is the dosing for leuprolide?

Not active PO; 1 mg SQ daily (prostate cancer); then 3.75 mg or 7.5 mg monthly/11.5 mg or 22.5 mg Q 3 months; 30 mg Q 4 months; 45 mg Q 6 months.

What are the ADRs of leuprolide?

Initial increase in sex steroids in early phase of therapy, injection site reactions, decreased bone density, worsening of lipid profile, headache, hyperglycemia, hot flashes, hypotension.

What are the DDIs of leuprolide?

Very few, if any.

What is the MOA of GnRH/LHRH antagonists?

Blocks pituitary GnRH receptors; inhibits secretion of gonadotropins and subsequent release of testosterone; rapid and profound decrease in testosterone without increased estrogen concentration.

What are the indications for GnRH/LHRH antagonists?

Advanced prostate cancer, endometriosis, ovulation induction, gonadotropin inhibition.

What are the warnings for GnRH/LHRH antagonists?

Allergy, increased QT interval.

What is the pregnancy category of GnRH/LHRH antagonists?

Pregnancy category X; avoid lactation.

What are the ADRs of GnRH/LHRH antagonists?

Injection site reactions, hot flashes, weight gain, increased LFTs, increased glucose, increased triglycerides, decreased hemoglobin, muscle pains.

What is the dosing of degarelix?

240 mg SQ x 1, then 80 mg SQ Q28 days.

What is the dosing of relugolix?

360 mg PO x 1, then 120 mg PO daily.

What are the specific DDIs of relugolix?

Avoid PgP inhibitors and strong CYP3A4 inducers.

What is ganirelix indicated for?

Prevents premature ovulation in women being given FSH for fertility.

What is elagolix indicated for?

Endometriosis.

What is the MOA of non-steroidal anti-androgens?

Competitively inhibits the action of androgens by binding to cytosolic androgen receptors in target tissues.

What are the indications for anti-androgens?

Add-on Rx after failure of LHRH agonist or LHRH antagonist or orchiectomy, short-term Rx to prevent tumor flare during early LHRH agonist, long-term with LHRH agonist as combined androgen blockade.

What are the ADRs of flutamide?

Diarrhea, breast tenderness, nausea, cases of fatal and nonfatal liver toxicity.

What are the ADRs of bicalutamide?

Nausea, breast tenderness, hot flashes, loss of libido, impotence.

What is the dosing of nilutamide?

150 mg tab used with surgical castration for metastatic prostate cancer (stage D2).

What are the CIs of anti-androgens?

Allergy, women, pregnancy.

What are the warnings for anti-androgens?

Severe hepatic injury -> LFTs Q month x 4, then Q 6 months, bleeding with warfarin (increased INR).

What are the ADRs of anti-androgens?

Hyperlipidemia, insulin resistance, diabetes, osteoporosis, increased fracture risk, anemia, increased fat mass, decreased muscle mass, loss of body hair, gynecomastia, hot flashes, decreased cognition, emotional changes, decreased libido, erectile dysfunction.

What are the indications for 2nd-generation anti-androgens?

Non-metastatic castration resistant prostate cancer.

What is the dosing of enzalutamide?

160 mg PO daily.

What is the dosing of apalutamide?

240 mg PO daily.

What is the dosing of darolutamide?

600 mg PO daily (with food and LHRH analog); decrease dose in renal or hepatic disease.

What are the CIs of 2nd-generation anti-androgens?

Allergy.

What are the warnings for 2nd-generation anti-androgens?

Falls and fractures, CAD, PRES syndrome.

What is the pregnancy category of 2nd-generation anti-androgens?

Category X; avoid lactation.

What are the ADRs of 2nd-generation anti-androgens?

Asthenia, fatigue, decreased appetite and weight loss, hot flushes, arthralgia, dizziness, vertigo, hypertension, headache, rash.

What are the DDIs of 2nd-generation anti-androgens?

Avoid strong CYP2C8 inhibitors, strong 3A4 inducers, monitor INR with warfarin.

What is the indication for abiraterone acetate?

CYP17 inhibitor used in combination with prednisone for metastatic castration-resistant prostate cancer who have received prior chemotherapy with docetaxel.

What are the CIs of abiraterone acetate?

Pregnancy, severe hepatic impairment.

What is the dosing of abiraterone acetate?

1000 mg PO daily (with food) with prednisone 5 mg PO BID; decrease dose to 250 mg PO daily with moderate hepatic impairment.

What are the warnings for abiraterone acetate?

Increased mineralocorticoid effects, adrenal suppression, hepatotoxicity, food increases abiraterone acetate 10 times.

What are the ADRs of abiraterone acetate?

Joint swelling, hypokalemia, hot flushes, diarrhea, hypertension, urinary frequency, arrhythmia.

What are the DDIs of abiraterone acetate?

CYP2D6 substrates that compete with abiraterone (2D6 inhibitor).

What is the MOA of anti-adrenal therapy?

Block enzymes in adrenals required for androgen synthesis, leading to PSA decrease in CRPC.

What is the MOA of aminoglutethimide?

Inhibits adrenal-mediated enzymatic conversion of cholesterol to pregnenolone, thereby decreasing adrenal corticosteroids, mineralocorticoids, estrogens, and androgens.

What is the MOA of ketoconazole?

An antifungal that inhibits the cytochrome P450 enzyme in the adrenal gland.

What are the ADRs of anti-adrenal therapy?

Adrenal insufficiency, therefore administer with hydrocortisone; impotence, pruritus, sedation, skin rashes, severe hepatotoxicity with ketoconazole.