Test 3 antineoplastics

• Cyclophosphamide (nitrogen mustards)
• Carmustine (nitrosureas)
• Procarbazine (methylhydrazine)
• Temozolomide (triazine)
• Cisplatin (Pt coordination complex)

• Methotrexate (folate antagonist)
• 5- fluorouracil (pyrimidine analogs (U,C))
• 6-Mercaptopurine

• Vincristine
• Paclitaxel
• Doxorubicin

Flutamide (antiandrogen)

Aldesleukin

rituximab

imatinib

MOA: DNA alkylation: mispairing, scission, inter/intrastrand x-linking (two war heads)

Uses: NHL, CLL, AML, Breast, Ovarian

S/E: myelosuppression, hepatic venooclusive disease (inc fibrin); N/V; hemorrhagic cysitis; neurotoxicity; alopecia; pulmonary fibrosis

PK: Requires activation via CYP286

MOA: DNA alkylation: mispairing, scission

Uses: Brain, HD, NHL, melanoma

S/E: myelosuppression, hepatic venooclusive disease, pulmonary fibrosis, leukemogenic, renal failure, N/V

PK: Breaks into two pieces, one alkylates DNA, other carbamoylated protein/inactivates AGT (MOR)

MOR: Alkyl guanine transferase (removes alkylat'n>> healthy DNA)

MOA: methylates DNA; free radical prod>> chromosome damage inhibition of DNA, RNA, and protein synthesis

Uses: HD, NSCLC, Brain (astrocytoma)

S/E: BMS (leukemia, thrombocytopenia), weak MAOI, 2ary leukemia, teratogen, disulfirum effect (octoberfest w/anabuse, tyramine>> N/V HTN, tachycardia, etc

MOA: bioactivated into diazomethane (methilates DNA, guanine)

Uses: brain (astrocytoma), melanoma

• S/E:
• BMS (thrombocytopenia, neutropenia) HA, fatigue

• PK:
• 98% bioavailability, penetrates BBB

• MOA:
• DNA adduct formation >> inhibit replication/transcription >> breaks, miscoding (G)

• Uses:
• Testicular, ovarian, cervix, bladder, N/SCLC

• S/E:
• BMS, peripheral neuropathy, ototoxicity, hypersensitivity rxn, nephrotoxicity (dec. w/NS hydration, diuresis, amifostine (protective)

• MOR:
• Loss of mismatch repair (apoptosis trigger)

• MOA:
• DHF inhibition (decreases DNA/RNA synthesis)

• Uses:
• ALL, CNS leukemia (IT), GTN--> chorion that surrounds baby, breast, NHL

• S/E:
• Myelosuppression, pneumonitis, mucositis (whole GI), hepatotoxicity, teratogenesis, meningismus (IT-->intrathecally, right into CSF), nephrotoxicity

• PK:
• Dose should be adjusted in those with decreased renal faiulre

• MOR:
• Polyglutanated and stays inside cell, DHFR gene amplification is clinically significant in patients with lung cancer, MRP

• MOA:
• Converted into 5- FDUMP (5-F-deoxyuridine monophosphate) (inhibitor of thymidylate synthase (U>>T); Decreased DNA synthesis

Uses: Colorectal, breast, gastric, pancreatic, esophageal

• S/E:
• N/V/D alopecia, myelosuppression, hand and foot syndrome (selective extravasation on palms/soles, they are RED!!)

• PK:
• people with low levels of dihydropyrimidine dehydrogenase can have very severe toxicity with 5-FU

• MOA:
• converted to 6-thioguanine nucleotides (inc. into DNA/RNA >> cytotoxicity)

• Uses:
• ALL

• S/E:
• myelosuppression, N/V/D, hepatotoxic

• MOA:
• bind tubulin and block ability to polymerize into microtubules

• Uses:
• HD, NHL, Brain, ALL

• S/E:
• fatal (IT, seizures, coma); alopecia, myelosuppression, neurotoxicity, constipation (damage ANS, peristalsis)

• PK:
• CYP3A4; dec dose 75% for hepatic dysfxn

• MOA:
• Bind microtubules and antagonize disassembly >> arrest in mitosis

• Uses:
• Ovarian, N/SCLC, breast, H/N, KS (kaposi)

• S/E:
• myelosuppression, peripheral neuropathy, mucositis (ulcers), hypersensitivity (50/50 EtOH:Castor oil vehicle)

• PK:
• CYP3A4, hep dysfxn dec. dose 50-75%

• MOA:
• DNA intercalation (>> single/dbl strand breaks); bind topo-II complx (dbl strand breaks); free radical production (esp. in presence of Fe)

• Uses:
• AML; ALL; HD; KS; Breast; Neuroblastoma

• S/E:
• BMS (dose lt'ing); extravasation (tissue necrosis), stomatitis, alopecia, 2ary AML, cardiotoxicity (arrhythmia, CHF, tx = Dexrazoxane (cardioprotect Fe chelator)

• PK:
• CYP3A4; hep dysfxn dec. dose 50%

• MOA:
• Androgen receptor antagonist

Use: Prostate (usually w GnRH analog)

• S/E:
• Nausea (mild); gynecomastia; hot flash; decreased libido, hepatotoxicity

PK: CYP3A4

• MOA:
• human recombinant IL-2; $ immune sys (inc. TNF, IL-1, IFNy for inhibiting tumor growth)

• Uses:
• RCC, melanom

• S/E:
• capillary leak syn (hypotension, dec. organ perfusion, edema); infections; BMS (RBC, platelets); mental status changes (irritability, confusion, depression); thyroid fxn impairment, arrhythmias

• PK:
• CYP3A4

• MOA:
• Fab binds CD20 on B cells, Fc stimulates the immune system for their lysis

• Uses:
• NHL, CLL, RA (b/c of B cells)

• S/E:
• arrhythmias, hypersensitivity rxns (hypotension, bronchospasm, angioedema), HepB infections, tumor lysis syn

• PK:
• CYP3A4

• MOA:
• Inhibit TK association w/Bcr-Abl (decreases proliferation, stimulates apoptosis)
• inhibit tyrosine kinase associated w/ EGFR (epidermal growth factor), ∴ ↓ proliferation & stimulates apoptosis

• Uses:
• CML, GIST, ALL

• S/E:
• Edema (periorbital, pulmonary) BMS, hepatotoxicity

• PK:
• CYP3A4