pharm onc

Mucositis common with...

prevents nausea/vomiting at level of CTZ

Prochlorperazine

Cyclophosphamide pharmacokinetics

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

LHRH (Leutinizing Hormone Releasing Hormone) agonist

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

Myelosuppression
Peripheral neuropathy, constipation, ileus, Alopecia
SIADH, Vesicant
Fatal if given intrathecally (Never!)
Liver Metabolism. Reduce dose if Total Bili > 3mg/dl

Myelosuppression, Peripheral Neuropathy
Hypersensitivity reactions
Capillary leak
Edema

Taxane therapeutic uses

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
Hepatic metabolism

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
Skin discoloration
Pulmonary fibrosis (those over 70 years old or have undergone chest irradiation, or underlying pulmonary disease).
Raynaud’s syndrome, Alopecia, Mucositis

Testicular cancer, Squamous cell carcinomas of the head and neck, cervix, skin, penis, and rectum
Lymphomas
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

FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

derivative of Rituximab which is radiolabeled with Ytrium

I-131 radiolabeled Rituximab

Advantages: Better efficacy, fewer doses.
Disadvantages: Toxicity (Neutropenia, thrombocytopenia, infection (30%); More labor

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.

Bevacizumab therapeutic use

GI perforation, intra-abdominal abscesses.
Wound dehiscence, a spontaneous separation of wound or surgical repair.
Hypertensive crisis
Nephrotic syndrome
Congestive heart failure, Myocardial Infarction
Weakness, Leukopenia

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
CYP3A4 substrate
Half-life (t1/2) = 12-36 hours

Myelosuppression
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)

Prodrug that can be used along w/ Lapatinib for Her2/neu breast cancer. Converted to 5-FU in tumor

Inhibits VEGF
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

Inhibits EGFR (Her2/neu)

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