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Mucositis common with...
5-FU, Busulfan, alkylating agents, radiation
prevents nausea/vomiting at level of CTZ
5HT3 Antag (Ondansetron), NK1 Antagonist (Aprepitant), Phenothiazines
- anti D2 receptor. Antiemetic and migraine treatment.
- Adverse: dystonias and orthostatic hypotension
activated via cytochrome P450. Inactivated by aldehyde dehydrogenase
MAO inhibitor and nonclassical alkylating agent
Nephrotoxicity, ototoxicity, N/V, peripheral neuropathies, myelosuppression
Pure estrogen receptor antagonist. Inhibits dimerization of the occupied receptor; thus there is no binding to the DNA. Effective in resistant tamoxifen patients. Monthly injection
Treatment of anti-estrogen resistant advanced breast cancer or as first line adjuvant in postmenopausal women.
Do not suppress mineralocorticoid or glucocorticoid production
- Non steroidal aromatase inhibitors Anastrozole and Letrozole
- Exemestane - Steroidal (irreversible inhibitor of aromatase)
LHRH (Leutinizing Hormone Releasing Hormone) agonist
Leuprolide, Goserelin. Inhibits synthesis of sex steroids in both men and women. Suppression of androgen synthesis. Reduction of PSA. Used mostly for prostate cancer; sometimes in combination with an antiandrogen (flutamide)
Nonsteroidal antiandrogen which blocks androgen at receptor site. Used in combination at the beginning of therapy with LHRH analogue for prostate cancer to prevent tumor flare
Nonsteroidal synthetic estrogen to suppress androgen synthesis
Most widely used agent for Colorectal cancer; alsobreast, bladder, esophagus. Can lead to mucositis and myelosuppression
Complex, poor oral bioavailability, thus only given I.V. Undergoes reduction by a dehydrogenase enzyme. Metabolism follows zero-order kinetics at high doses
Vinca alkaloid MOA
- Binds to the microtubular protein tubulin in a dimeric form
- The drug-tubulin complex adds to the forming end of the microtubules to terminate assembly
- Depolymerization of the microtubules occurs
Peripheral neuropathy, constipation, ileus, Alopecia
Fatal if given intrathecally (Never!)
Liver Metabolism. Reduce dose if Total Bili > 3mg/dl
Adverse effects of Vinca alkaloids
Myelosuppression, Peripheral Neuropathy
Toxicities of Taxanes
Taxane therapeutic uses
- Paclitaxel- ovarian (with cisplatin) and advanced breast cancer, lung cancer, and Kaposi’s sarcoma
- Docetaxel- advanced breast cancer, head and neck cancer, gastric cancer, bladder cancer, platinum refractory ovarian cancer.
High-affinity binding to DNA through intercalation, resulting in blockade of DNA and RNA synthesis
DNA strand scission via effects on Topoisomerase II
Binding to membranes altering fluidity
Generation of oxygen radicals
Binds to DNA through an antibiotic-Mg2+ complex
This interaction interrupts DNA-directed RNA synthesis
Adverse effects: liver toxicity, bleeding disorder, hypocalcemia
Use: testicular cancer, hypercalcemia
Bioreductive alkylating agent that undergoes metabolic reductive activation through an enzyme-mediated reduction to generate an alkylating agent that cross-links DNA.
Adverse Effect: renal toxicity, lung fibrosis, bone marrow toxicity, hemolytic anemia.
Use: bladder tumors, gastric adenocarcinoma, hypoxic tumor.
Binds to double stranded DNA through intercalation between adjacent guanine-cytosine base pairs
Inhibits all forms of DNA-dependent RNA synthesis
Inhibits DNA transcription
Adverse effects: oral ulcers, sun sensitivity, immunosuppression
Use: Wilm’s tumor
Acts through binding to DNA, which results in single and double strand breaks following free radical formation and inhibition of DNA synthesis
accumulation of cells in G2
Lethal anaphylactoid reactions
Pulmonary fibrosis (those over 70 years old or have undergone chest irradiation, or underlying pulmonary disease).
Raynaud’s syndrome, Alopecia, Mucositis
Bleomycin adverse effects
Testicular cancer, Squamous cell carcinomas of the head and neck, cervix, skin, penis, and rectum
Intracavitary therapy in ovarian and breast cancers
Antibodies for CD20
Antibodies for CD33
Antibodies for CD52 (found on all mature lymphocytes)
Antibody for VEGF
Antibody for EGFR
Non-Hodgkin's lymphoma treatment
- Hydoxydaunorubicin (doxorubicin)
- Oncovin (vincristine)
FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
derivative of Rituximab which is radiolabeled with Ytrium
For CD20. Ibritumomab
I-131 radiolabeled Rituximab
For CD20. Tositumomab
Advantages: Better efficacy, fewer doses.
Disadvantages: Toxicity (Neutropenia, thrombocytopenia, infection (30%); More labor
Radiolabeled Rituximabs: Ibritumomab and Tositumomab
1,000 x as toxic to CD33 cells as is doxorubicin
Chronic Lymphocytic Leukemia (CLL), T-Cell Lymphoma and Cutaneous T-Cell Lymphoma.
Toxicity may include Infusion Related Events, which may include respiratory or cardiac death.
Aims at CD52. Alemtuzumab
Bevacizumab therapeutic use
VEGF Ab. colon cancer, lung cancer, breast cancer
GI perforation, intra-abdominal abscesses.
Wound dehiscence, a spontaneous separation of wound or surgical repair.
Congestive heart failure, Myocardial Infarction
Chimeric (mouse/human) monoclonal antibody. EGFR inhibitor. IV infusion for metastatic colon cancer, head and neck cancer
Severe acne rash that is reversible. Infusion rxn that may be mediated by H1 histamine receptor. Toxicity can be prevented via diphenhydramine
Cardiac Toxicity, Increased risk for cardiac death.
Contraindicated with Anthracyclines.
Cost: Approx. $70,000-$100,000 per year.
highly protein bound
Half-life (t1/2) = 12-36 hours
Small molecule tyrosine kinase inhibitors. -nibs
Fluid retention & edema (dose-related)
Pleural effusions, ascites, pulmonary edema, rapid weight gain, CHF (rare)
Nausea, diarrhea, abdominal pain
Musculoskeletal pain, myalgias
Rash, Hepatotoxicity (can be severe)
Adverse effects of Imatinib
Prodrug that can be used along w/ Lapatinib for Her2/neu breast cancer. Converted to 5-FU in tumor
Labeled indications: Advanced renal cell carcinoma, Unresectable hepatocellular carcinoma
Inihibts VEGF and c-kit
Labeled indications: GI stromal tumor w/ failure or intolerance to imatinib
Advanced renal cell carcinoma
Myelosuppression, GI effects, hand foot syndrome, hypertension, bleeding, hair color changes
Myelosuppression, GI effects, hand foot syndrome, bleeding, incr QT, hypothyroidism, skin discoloration, and venous thromboembolic events
Drugs that lead to hand foot syndrome
- 5-FU, capecitabine, cytarabine, doxorubicin
- TKIs: sorafenib and sunitinib.
Inhibits EGFR (Her2/neu)
Lapatinib, Gefitinib, Erlotinib
Approved world-wide for non-small cell lung carcinoma (NSCLC).
EGF tyrosine kinase receptor (EGFR) inhibitor
Side effects: Acne, GI, asthenia.
INHIBITS HER-1 (EGFR)
Non-small cell lung cancer (NSCLC) – locally advanced or metastatic in patients who have failed at least one prior chemotherapy regimen
Pancreatic cancer – locally advanced, unresectable or metastatic in combination with gemcitabine
Reversible inhibitor of 26S Proteosome
Increases cellular protein, including tumor suppressors. May prevent degradation of pro-apoptotic molecules, allowing continued programmed cell death in neoplastic cells
GI upset and asthenia, a state of general weakness.
Peripheral neuropathy with pain
Shingles, Neutropenia, Thrombocytopenia
analog of cytidine, and is incorporated into DNA during replication and RNA during transcription.
Azacytidine inhibits methyltransferase and causes demethylation of its segment of DNA and RNA.
Indicated for myelodysplastic syndrome of neutropenia, thrombocytopenia, anemia
GI symptoms, Neutropenia, Thrombocytopenia, Liver dysfunction
side effects of Azacytidine