Chemotherputics

• Nitrogen mustard -> causes alkylation of DNA primarily at N-7 of G which leads to misreading, depurination, and double strand breaks
• Stable enough for oral administration

• Nitrogen mustard -> causes alkylation of DNA primarily at N-7 of G which leads to misreading, depurination, and double strand breaks
• Stable enough for oral administration

• Nitrogen mustard -> causes alkylation of DNA primarily at N-7 of G which leads to misreading, depurination, and double strand breaks
• Must be activated by hepatic cytochrome p450
• No hepatotoxicity because converted to inactive metabolite in the liver
• Toxicities: pulmonary fibrosis, cystitis

• Nitrosourea -> heterobifunctional compound that causes alkylation, DNA crosslinking, and carbamoylation of protiens
• Cross readily into CNS -> Tx for malignant glioma
• Toxicity: Delayed but severe hematopoietic depression

• Nitrosourea -> heterobifunctional compound that causes alkylation, DNA crosslinking, and carbamoylation of protiens
• Cross readily into CNS -> Tx for malignant glioma
• Toxicity: Delayed but severe hematopoietic depression

• Platinum coordination complex -> potent alkylating activity that causes a variety of cross links
• Toxicities: myelosuppression, nephrotoxicity, ototoxicity
• Administer with amifostin (free radical scavenger) to attenuate nephrotoxicity

• Cisplatin analog that is not crss-resistant
• Platinum coordination complex -> potent alkylating activity that causes a variety of cross links
• Toxicities: myelosuppression, nephrotoxicity, ototoxicity
• Administer with amifostin (free radical scavenger) to attenuate nephrotoxicity

• Platinum coordination complex -> potent alkylating activity that causes a variety of cross links
• Toxicities: myelosuppression, nephrotoxicity, ototoxicity
• Substantially less renal toxicity than cisplatin or oxaliplatin

• Nonspecific alkylator (DNA, RNA, protien)
• Metabolized to active form by hepatic enzymes
• Toxicities: Myelosuppression, MAO inhibitor, carcinogenicity

• Vinca alkaloid -> depolymerizes microtubules -> inihbits movement and mitosis
• Toxicities: Neurotoxicity, stimulation fo ADH release
• Resistance: MDR

• Vinca alkaloid -> depolymerizes microtubules -> inihbits movement and mitosis
• Toxicities: myelosuppression, mucositis
• Resistance: MDR

• Taxane -> stabalizes the assembly of microtubules by inhibiting disassembly
• Toxicities: Neutropenia, mucositis, cardiac arrythmia in pnts who have recieved other cardiotoxic drugs
• Derived from the bark of the western yew tree

• Semisynthetic analogue of paclitaxel
• Taxane -> stabalizes the assembly of microtubules by inhibiting disassembly

• Epothilone -> binds directly to beta-tubulin and promotes polymerization and stabalizes microtubule, arresting cells in G2/M
• Toxicities: neutropenia, cardiotoxicity, peripheral neuropathy

• Epipodophyllotoxins -> Inhibition of topoisomerase II
• Toxicities: leukopenia, thrombocytopenia
• Resistance: MDR
• Semisynthetic derivatives derived from mandrake plant

• Epipodophyllotoxins -> Inhibition of topoisomerase II
• Toxicities: leukopenia, thrombocytopenia
• Resistance: MDR
• Semisynthetic derivatives derived from mandrake plant

• Camptothecin derivatives -> Inhibition of topoisomerase I
• Prodrug
• Effective in metastatic colorectal cancer
• Toxicities: neutropenia, diarrhea
• Resistance: MDR

• Camptothecin derivatives -> Inhibition of topoisomerase I
• Effective in ovarian and small cell CA of lung
• Toxicities: neutropenia, diarrhea
• Resistance: MDR

• Antibiotic
• Mechanism: DNA intercalation, introduction of single stranded breaks
• Toxicities: Cumulative cardiotoxicity that can manifest as arrythmias or digitalis unresponsive heart failure. Reduce cardiac damage by giving with Dexrazoxane

• Antibiotic
• Mechanism: DNA intercalation, introduction of single stranded breaks
• Toxicities: Cumulative cardiotoxicity that can manifest as arrythmias or digitalis unresponsive heart failure.
• Reduce cardiac damage by giving with Dexrazoxane

• Iron chelator that inhibits free radical formation and can be used to reduce cardiac damage, as well as to minimize extravasation reactions
• Given with daunorubicin and doxorubicin to minimize cardiotoxicity

• Antibiotic
• Mechanism: Depurination and depyrimidation; both single and double stranded breaks are introduced
• Toxicities: Subacute or chronic pneumonitis, lesions of the skin
• Resistance: Over expression of bleomycin hydrolase

• Folic acid analog that is a competitive inhibitor of dihydrofolate reductase
• Cells in S phase cannot synthesize DNA
• Toxicities: fatal myelosuppression; renal, hepatic and neuro toxicity; teratogenicity
• Resistance: Increased DHFR activity

• Used to abort MTX toxicity by supplying reduced folate to cells, thus bypassing the inhibited reductase.
• Can also be used to potentiate the activity of 5-FU

• Potent suicide inhibitor of thymidylate synthase
• Toxicities: myelosuppress, GI distress, acute or chronic conjunctivitis
• Resistance: Overexpression of TS

5-FU prodrug whose final step of activation is catalyzed by thymidine phosphorylase, an enzyme elevated in certain tumors

• Recognized as deoxycytidine by cytosine kinase, phosphorylated, and becomes a potent inhibitor of DNA polymerase and when incorporated into DNA causes defective ligation and premature chain termination
• Toxicities: Myelosuppression, nausea, vomiting, GI ulceration, and seizures
• Resistance: decreased cytosine kinase activity, increased cytosine deaminase activity

• 2'-2'-difluorodeoxycytidine
• Similar to cytosine arabinoside
• Good activity in advanced breast cancer, non-small-cell lung cancer, pancreatic adenocarcinoma, and ovarian carcinoma

• Inhibits DNA methyltransferase resulting in hypomethylation; incorporated into RNA
• Good for Tx of myelodysplastic syndrome

• Purine analog
• Converted by hypoxanthine-granine-phosphoribosyl transferase to monophosphates:
• Feedback inhibit de novo purine synthesis; competitively inhibit biosynthetic reactions, converted to triphosphates that are incorporated into DNA and RNA
• Toxicity: myelosuppression, hepatotoxicity
• Resistance: HPRT mutations, overexpression of thiopurine methyltransferase

• Catalyzes the conversion of asparagine to aspartate
• In some cancer cells asparagine is an essential amino acid (lack of asparagine synthetase)
• Pegylated form has longer t1/2
• Toxicities: reduction in concentration of secreted protiens, hypersensitivity, hepatotoxicity

• Competitively blocks the ATP-binding site of c-abl tyrosine kinase
• Tx for CML
• Toxicities: congestive heart failure, myelosuppression

• Inhibitor of EGF receptor-associated tyrosine kinase
• Tx for non-small cell lung cancer and pancreatic cancer
• Toxicity: congestive heart failure

• Inhibitor of EGF receptor-associated tyrosine kinase
• Tx for non-small cell lung cancer and pancreatic cancer
• Toxicity: congestive heart failure

• Inhibitor of BRAF serine-threonine kinase
• Good for Tx of melanoma

• Chimeric monoclonal Ab directed against the EGFR
• For use in head and neck and metastatic colorectal cancer

• Induces antibody-dependent cell-mediated cytotoxicity
• For the tx of p185-HER2 overexpressing breast cancer
• Toxicity: cardiotoxicity, especially when used with or after anthracyclines

• Humanized monoclonal Ab directed against VEGF
• designed to inhibit angiogenesis
• effective in tx of lung, colon, and kidney cancer
• use associated with increased risk of thromboembolic events

• Recombinant anti-CD20 monoclonal Ab that promotes complement mediated lysis of malignant B-cells
• Use can result in HBV reactivation

Recombinant monoclonal Ab directed against myeloid cell surface Ag CD33

• Histone deacetylase inhibitor
• Used to tx cutaneous T cell lymphoma

Proteosome inhibitor used for tx of multiple myeloma and mantle cell lymphoma

First line therapy for promyelocytic leukemia

• Selective estrogen receptor modulator
• Competitive partial agonist inhibitor
• In breast tissue acts like an antagonist, in endometrial tissue acts like an agonist
• Must be activated by CYP2D6
• Use in postmenopausal women with estrogen receptor positive breast cancer
• Only use for 5 years
• Adverse effects: Endometrial CA, thromboembolic events

• SERM
• As effective as tamoxifen
• Lower incidence of uterine cancer and fewer blood clots

• Pure estrogen receptor antagonist
• Given once a month IM
• Geven to postmenopausal women whose cancer has progressed on tamoxifen or other anti-estrogen

• Selective and irreversible inhibitors of aromatase
• Used only for postmenopausal women
• Continue to be effective beyond 5 years
• No risk of endometrial cancer or thromboembolic event
• Approved as first line therapy or as an alternative to tamoxifen

• Selective and irreversible inhibitors of aromatase
• Used only for postmenopausal women
• Continue to be effective beyond 5 years
• No risk of endometrial cancer or thromboembolic event
• Approved as first line therapy or as an alternative to tamoxifen

• Selective and irreversible inhibitors of aromatase
• Used only for postmenopausal women
• Continue to be effective beyond 5 years
• No risk of endometrial cancer or thromboembolic event
• Approved as first line therapy or as an alternative to tamoxifen

• Humanized monoclonal Ab against HER2/erbB-2 receptor
• Side effects: cardiomyopathy when combined with anthracyclines

• Orally active tyrosine kinase inhibitor that targets both erbB receptors
• Used for the tx of advanced breast cancer expressing high levels of HER-2 that no longer respond to trastuzumab

• GnRH analog
• For use in prostate cancer - equivalent to surgical castration or diethylstilbestrol tx
• Initial surge of LH and FSH compensated by administering biclutamide

• GnRH analog
• For use in prostate cancer - equivalent to surgical castration or diethylstilbestrol tx
• Initial surge of LH and FSH compensated by administering biclutamide

• GnRH antagonist
• Will inhibit LH and FSH release and testosterone production without a flare

• Pure androgen antagonist
• Prevents binding of endogenous androgens to the androgen receptor
• No intrinsic steroidal activity
• Side effects: diarrhea, gynecomastia, hepatotoxicity (rare)

• Newer nonsteroidal antiandrogen
• Could be more effective than flutamide
• Less side effects than flutamide