Cancer drugs Flashcards
Tamoxifen
- SERM (selective estrogen receptor modulator)
- Antagonist at breast, agonist at other tissues
- Prodrug (2D6, 3A4)
- Keeps cells in G0 or G1 phases and prevents them from dividing
- May also be anti-angiogenic
- Used in hormone positive patients (men and women)
- Used in early cancers alone, and in late stage with other agents
- May be used for prophylaxtic used in those with high risk of cancer development
- Increases the production of clotting factors→ thromboembolisms
- Increases TG levels
- Inc endometrial cancers
Raloxifene
• SERM
• Antagonist at breast and uterine tissues, agonists at other tissues
• Used for post-menopausal women and for osteoporosis
o Not as great for preventing invasive breast cancers from forming
• High first pass effect, and highly protein bound
• ADR: Hot flashes, leg cramps, less likely for thromboembolism to occur
Goserelin
- Ovarian ablation drugs
- May allow some hormonal therapies to work better
- Produces symptoms of menopause since the ovaries can’t produce estrogen
- Used in breast and prostate cancers
- Given in injectable form either 1 month or 3 month intervals
- Normal function should return after drug is stopped ~ 3 months
- Initially causes an increase in estrogen or testosterone
Leuprolide
- Ovarian ablation drugs
- Not used for breast cancer, only for prostate cancer
- Given 1/day SC
- Normal function should return after drug is stopped ~ 3 months
- Initially causes an increase in estrogen or testosterone
Anastrozole
• Aromatase inhibitor
o Used in hormone sensitive breast cancers for post menopausal women
• Reversible inhibitor
o Imidazole ring interacts with iron on the heme groups and prevents oxidation of normal substrates
• Nonsteroidal
• Used alone or after tamoxifen therapy
• Given orally
• Metabolized by CYP
• Inhibits CYP 3A4, 1A2, 2C9
• ADR: bone weakness, N/V, muscle weakness, hot flashes, vaginal dryness
Letrozole
• Aromatase inhibitor
o Used in hormone sensitive breast cancers for post menopausal women
• Reversible inhibitor
o Imidazole ring interacts with iron on the heme groups and prevents oxidation of normal substrates
• Nonsteroidal
• More potent than anastrozole
• Metabolized by CYP 2A6, 3A4
• Inhibits 2A6 and 2C19
• ADR: bone weakness, N/V, muscle weakness (less), hot flashes, vaginal dryness
Exmestane
• Aromatase inhibitor
o Used in hormone sensitive breast cancers for post menopausal women
• Suicide inhibitor (irreversible)
• Steroidal
• Poor absorption, but can be increased with high fat meal
• Metabolized by CYP 3A4
• ADR: hot flashes, N, Muscle pain
Trastuzumab
• Used in patients with metastatic breast cancer that have overexpression of HER2 receptors
• Given IV
• Its antibodies bind to the HER2 receptors on the breast cancer cells and are then recognized by phagocytic cells and are destroyed
• Can also bind to HER2 closer to cell membrane and prevent kinase pathways from occurring allowing apoptosis to occur more readily
o Would increase activity of other anticancer agents
• ADR: Cardiomyopathy, fever, chills, infections, increased cough, HA, rash, insomnia, D
Mertansine
- Used for patients that are resistant to Transtuzumab and taxanes that are HER2 positive metastatic cancer
- Tubulin inhibitor→ prevents cells from dividing→ death
- ADR: muscle pain, thrombocytopenia, HA, fatigue, increased liver enzymes, constipation
Pertuzumab
- Monoclonal antibody directed toward HER2 receptor binds distally and prevents dimerization
- Can be used with trastuzamab and docetaxol since binding sites are different
- Given IV
- DC if LVEF drops below 40% (cardiotoxic)
- ADR: D/N, hair loss, decreased WBC, fatigue, rash
Imatinib
• Used in CML (chronic mylogenous leukemia)
• Inhibits tyrosine Kinase by binding to the ATP binding site and prevents substrate from binding
o Useful for patients in chronic state, if they are in blast phase, will delay death by several months
• Metabolized by CYP 3A4, substrate for Pgp
• Resistance is due to tyrosine Kinases with altered amino acids which prevent the drug from binding
• ADR: ascites, neutropenia, thrombocytopenia, rash, pulmonary edema
Lapatinib
- Tyroskine Kinase inhibitor
- Used in breast cancers that overexpress HER2 for patients already recieveing capecitabine
- Used in post menopausal women who are already receiving hormonal therapy
- ADR: Skin rash, Diarrhea, decrease in LVEF (rare)
Bevacizumab
• Binds VEGF (angiogenic growth factors) and destroys them
• Monoclonal antibody
• Shuts of blood delivery to interior tumor → cell death (hopefully)
• Other agents should be used to kill exterior cells
• Used to treat colon and rectal cancers
• ADR: HTN, thrombosis, bleeding
o TONS of ADRS
Mechlorethamine
o Nitrogen Mustards
o Dialkylating agents (1 mustard- 2 nucleophiles)
o Can’t be given orally
o Given IV for leukemia/lymphomas
o Can be injected straight into solid mass tumor
o Effective from G0- M phase (not cell cycle specific agents)
o Less selective and more likely to mutate DNA
o Antidote= sodium thiosulfate
Cyclophosphamide
o Nitrogen Mustards o Used in breast cancer o Prodrug o Dose limiting myelosupression o Can be given orally and IV o Effective from G0- M phase (not cell cycle specific agents) o Less selective and more likely to mutate DNA F
Ifosfamide
o Nitrogen Mustards
o Used in other cancers
o bladder and nephrotoxicities are seen
o Effective from G0- M phase (not cell cycle specific agents)
o Less selective and more likely to mutate DNA
5-fluorouracil
- Antimetabolites- Pyrimidine drug
- Block the conversion of uridine to thymidine
- Forms a covalent bond
- Targeting thymidylate synthase inhibits the formation of DNA
- Replication and cell division
- Given IV or topically
- Used in Breast cancer, colorectal cancer, stomach, pancreatic, and basal cell cancers
- Can distribute to CNS
- Triphosphate is encorporated into DNA and Ribose triphosphate in RNA
- MOR: increased thymidylate synthase concentrations or decrease in folate substrate or increased concentrations of DPD
- Myelosuppression is dose limiting
- ADR: mucositis, D, hand food syndrome
Floxuridine
- Block the conversion of uridine to thymidine
* Antimetabolites- Pyrimidine drug
Capecitabine
- Antimetabolites- Pyrimidine drug
- Prodrug
- Block the conversion of uridine to thymidine
- Some activation steps take place at a higher rate in tumor tissues leading to selective accumulation
- Given orally
- Used for breast cancer and colorectal cancer
- Myelosuppression is dose limiting
- ADR: mucositis, D, hand food syndrome:
Methotrexate
- Competitively inhibits the binding of substrate (folic acid) to DHFR
- Reduces synthesis of nucleic acid bases
- Purine synthesis is inhibited
- Taken up by active transport
- NH2 is electron donating and increases the basicity which allows for protonation at physiologic PH
- Increase affinity
- ~ irreversible inhibition
- Given IV or orally
- Used to treat acute lymphoblatic and myeloblastic leukemias and other lymphomas and sarcomas, Breast cancer, bladder cancer, colorectal and head and neck cancers
- MOR: decreased carrier mediated transport into cells or increased concentrations of DHFR
- ADR: bone marrow suppression, pulmonary fibrosis, GI ulceration, myelosupression, N/V HA, renal toxicity, acute cerebral dysfxn, rash, hyperpigmentation
Pemetrexed
- Inhibits DHFR, Thymidlate synthase and GARFT
- Inhibits purine synthesis
- Taken up into tumor cells by reduced folate carrier systems and converted into polyglutamate which stays within the cells
Trimetrexate
Antifolate drug
Doxorubicin
o Anthracyclines
o MOA:
• Intercalation
• inhibition of topoisomerase II→ strand breakage
o Specific for S phase of cell cycle
o MOR: decreased concentrations of topoisomerase II and mutations of that enzyme
o Cardiotoxicity is dose limiting→ CHF
o Can be used for a wide variety of cancers including breast cancer
o Substrate for PGP
Epirubricin
o Anthracyclines
o Decreased cardiotoxicity
o Increased clearance, decreased toxicity
o MOA:
o Specific for S phase of cell cycle
o Given IV for breast cancer
• Can be used for other types of cancer—still has a limited use though
o Can be used in larger doses with LESS cardiotoxicity
