Cancer Chemotherapy Flashcards
Alkylating agents
Cyclophosphamide, cisplatin, Procarbazine, Dacarbazine, Busulfan, Carmustine
Antimetabolites
5-fluorouracil, methotrexate
gemcitabine, 6-mercaptopurine, cytarabine
Natural products
Etoposide, paclitaxel, vincristine, Vinblastine
Antitumor antibiotics
Bleomycine, doxorubicin, mitomycin, actinomycin D,
Miscellaneous
Imatinib, cetuximab
Hormonal
Prednisone, tamoxifen
Log-kill hypothesis
anticancer drugs kill a fixed proportion of a tumor cell population, not a fixed number of tumor cells
Cell Cycle Nonspecific Drugs (CCNS)
G0 phase (CCNS)
Cisplatin
Antitumor antibiotics,
Nitrosureas (Lomustine, carmustine)
Cell cycle Specific Drugs (CCS) S phase
S phase (66 MECH)
6-mercaptopurine, 6 thioguanine, Methotrexate
Etoposide, Cytarabine, Hydroxyurea,
Cell cycle Specific Drugs (CCS) G2 phase
Bleomycine
Cell cycle Specific Drugs (CCS) M phase
Vinblastine
Vincrisine
Paclitaxel
Use of chemotherapy in patients with localized cancer before performing local therapy (surgery)
Neoadjuvant Chemotherapy
Chemotherapy done after local treatment procedures such as surgery or radiation
Adjuvant chemotherapy
Rescue drug for methotrexate toxicity
Leucoverin
Rescue drug for cyclophosphamide toxicity
MESNA (mercaptoethane sulfate)
Rescue drug for doxorubicin toxicity
Dexrazoxane
Rescue drug for Cisplatin toxicity
Amifostine
Class Alkylating agent
MOA: Forms DNA cross-links resulting in inhibition of DNA synthesis and function.
Uses: Non-hodgkin’s lymphoma, CLL
AE: bone marrow suppression, HEMORRHAGIC CYSTITIS
Cyclophosphamide
Class Alkylating agent
MOA: Forms DNA cross-links resulting in inhibition of DNA synthesis and function.
Uses: Testicular CA, Ovarian CA, Advanced colon CA
AE: Nephrotoxicity
Cisplatin
Advanced colon CA (Oxaliplatin)
Class Alkylating agent
MOA: Forms hydrogen peroxide w/c generates free radicals that cause DNA strand scission
Uses: Hodgkin’s lymphoma, Non-hodgkin’s lymphoma
AE: Leukemogenic, Disulfiram rxn, BMS
Procarbazine
Class Alkylating agent
MOA: Forms hydrogen peroxide w/c generates free radicals that cause DNA strand scission
Uses: Hodgkin’s lymphoma, Non-hodgkin’s lymphoma
AE: BMS, Phototoxicity, Flu-like syndrome
Dacarbazine
Class Alkylating agent
MOA: Forms DNA cross-links resulting in inhibition of DNA synthesis and function.
Uses: CML
SE: Pulmonary fibrosis, Adrenal insufficiency , Skin pigmentation
Notes: SPAREs the bone marrow
Busulfan
Class Alkylating agent
MOA: Forms DNA cross-links resulting in inhibition of DNA synthesis and function.
Uses: BRAIN TUMORS, melanoma, skin CA
SE: CNS toxicity
Carmustine
- highly lipophilic, able to pass the BBB
Class: Antimetabolite, DMARD
MOA: Inhibits dihydrofolate reductase. Decrease synthesis of thymidylate, AA, purine nucleotides.
Uses: ChorioCA, Primary CNS lymphoma, RA, Psoriasis, Ectopic pregnancy
SE: BMS
Methotrexate
Class: Antimetabolite
MOA: Inhibits de novo purine nucleotide synthesis. Activated by HGPRT.
Uses Acute Leukemias (ALL, AML), CML
SE: BMS, Hepatotoxicity
6 Mercaptopurine (purine)
6 MP metabolism is inhibited by?
Allopurinol and febuxostat
Class Antimetabolite
MOA Inhibits thymidylate synthase
Uses: Colorectal CA, Bladder CA, Skin CA (basal cell ca, actinic keratoses)
SE: BMS
5 Fluorouracil (pyrimidine)
Class Antimetabolite
MOA: Inhibits DNA synthesis and repair. Inhibits ribonucleotide reductase with reduced formation of dNTPs.
Uses: Acute leukemias (ALL,AML), CML in blast crisis
Notes: Most specific for S phase cell cycle
Cytarabine (pyrimidine)
Class Antimetabolie
MOA: Inhibits DNA synthesis and repair. Inhibits ribonucleotide reductase with reduced formation of dNTPs.
Uses: Pancreatic CA
Gemcitabine
Class: Vinca Alkaloid MOA: Prevents microtubule assembly. Causes cell arrest at metaphase Use: Acute Leukemias, Lymphomas SE: Peripheral neuritis, paralytic ileus Note: Spares Bone marrow
Vinblastine
Class: Vinca Alkaloid
MOA: Prevents microtubule assembly. Causes cell arrest at metaphase
Uses: Testicular CA, Kaposi’s sarcoma
SE: BMS
Vincristine
Class: Podophyllotoxin
MOA: Inhibits DNA topoisomerase II. Inhibits mitochondrial electron transport.
Uses: Lung CA, Prostate CA, Hodgkin’s lymphoma
SE: BMS, GI irritation, Alopecia
Etoposide
Class Camptothecin
MOA Inhibits topoisomerase I
Uses: Advance ovarian ca (2nd line), small cell lung ca
Metastatic Colorectal CA
Topotecan: Advance ovarian ca (2nd line), small cell lung ca
Irinotecan: Metastatic Colorectal CA
Class: Taxane
MOA: interferes with mitotic spindle. Prevents microtubule disassembly into tubulin monomers.
Uses: Advance breast and ovarian CA
Paclitaxel
SE of Paclitaxel
Neutropenia, thrombocytopenia, peripheral neuropathy
SE of Docetaxel
Neurotoxicity, BMS
Class: Antitumor antibiotic
MOA: generates free radicals, w/c cause DNA strand breaks, Intercalates with DNA
Use: Testicular CA
SE: Pulmonary fibrosis
Notes: Specific for G2 phase of cell cycle
Bleomycin
Class: Antitumor antibiotic
MOA Binds to dsDNA. Inhibits DNA-dependent RNA synthesis. CCNS
Use: Melanoma, Wilm’s Tumor, Rhabdomyosarcoma
SE: BMS
Actinomycin D
Class Tyrosine Kinase Inhibitors
MOA: Inhibits tyrosine kinase activity of the protein product of bcr-abl oncogene in CML; Inhibits c-kit tyrosine kinase in GIST
Use: CML, GIST
SE: Fluid retention, Drug interactions
Imatinib
Class Monoclonal antibody
MOA: acts against breast ca cells that overexpress the HER2/neu receptor for epidermal growth factor
Uses: Metastatic breast CA
SE: Cardiotoxicity (CHF)
Trastuzumab
Class: Monoclonal antibody
MOA: inhibits binding of VEGF to VEGFR leading to inhibition of VEGF signaling. Inhibits tumor vascular permeability but enhances tumor blood flow and drug delivery
Use: Metastatic Colorectal CA, Non-small cell Lung CA, Diabetes retinopathy
SE: Gastrointestinal perforation
Bevacizumab
Class: Monoclonal antibody
MOA: Binds to surface protein in NHL cells. Induces complement mediated lysis. Direct cytotoxicity and induction of apoptosis
Uses: Nonhodgkins lymphoma (low grade)
Rituximab
Class Interferon
MOA: Endogenous glycoproteins with antineoplastic, immunosuppressive and antiviral actions
Uses: Hair cell leukemia, T-cell lymphoma
SE: Neurologic dysfunction, alopecia, myalgia, depression
Notes: CI include autoimmune disease, history of cardiac arrhythmias and pregnancy
Interferon Alpha
Class: substrate-depleting enzyme
MOA: depletes serum asparagine
Uses: ALL
SE Acute pancreatitis
Asparaginase
Class Vitamin A derivative MOA: Allows DNA transcription and differentiation of immature leukemic promyelocytes into mature granulocytes (differentiation therapy) Uses: Acute promyelocytic leukemia SE: Retinoic acid syndrome Notes: Only vitamin that can cure cancer Does not directly kill cancer cells
All trans retinoic acid
Retinoic Acid Syndrome
Dyspnea, fever, wt gain, peripheral edema
DOC Retinoic Acid Syndrome
Dexamethasone
MOA: suppresses inflammation and immune response. May trigger apoptosis and work on nondividing cancer cells
Use: CLL, Hodgkin’s lymphomas
SE: adrenal suppression, growth inhibition, muscle wasting
Prednisone
Class: Selective Estrogen Receptor modulator
MOA: Estrogen antagonist actions in breast tissue and CNS. Estrogen agonists effects in uterus, liver & bone
Uses: Hormone responsive breast ca
SE: Endometrial hyperplasia, endometrial ca
Notes: prevents osteoporosis and decrease risk for atherosclerosis
Tamoxifen
Class: Androgen antagonist
MOA Competitive antagonist at androgen receptor
Uses: Prostate CA, surgical castration
SE: gynecomastia, hot flushes
Flutamide
Surgical castration (nilutamide)
Notes: less hepatotoxicity with bicalutamide and nilutamide
GnRH analogs (leuprolide) must be co-administered with flutamide to prevent acute flare-up of prostate CA
Class: GnRH analog
MOA: Increased LH and FSH secretion with intermittent administration. Reduced LH and FSH secretion with prolonged continuous administration
Uses: Prostate CA, Precocious puberty
SE: Hot flushes, sweats, headache,
Leuprolide
Class: Estrogen synthesis inhibitor
MOA: Reduces estrogen synthesis by inhibiting aromatase
Uses: Breast CA, Precocious puberty
Notes: effective against Breast CA that have become resistant to tamoxifen
Anastrozole
