Cancer III Flashcards
What do DNA intercalating agents do?
Bind DNA through intercalation between specific bases, blocking DNA, RNA or both synthesis; cause DNA strands to break and interfere with cell replication; CCNS
Dactinomycin (Actinomycin D, Cosmegen): Mech, Thera, Important SE’s, SE’s, Misc
Class:
Mech: Intercalates G-C base pairs of DNA, interfering with DNA-dependant RNA polymerase; also causes ssDNA breaks
Thera: Pediatric tumors (Wilms’ tumor, rhabdomyosarcoma Ewing’s sarcoma); choriocarcinoma in women
Important side effects: Hematopoietic suppression with pancytopenia
Other side effects: Anorexia, nausea, vomiting
Daunorubicin (Cerubidine)
Class: Anthracyclines
Mech: Intercalate between DNA base pairs and donate electrons to O2 to form superoxide; superoxide reacts with itself to form H2O2 –> cleaved in the presence of Fe to form OH radical, which cleaves DNA
Thera: AML
Important SE’s: Irreversible dose-dependent cardiotoxicity; alopecia
Other SE’s: Myelosuppression (neutropenia), stomatitis, GI disturbances
Misc: Dexrazoxane is cardio-protective
Idarubicin (Idamycin)
Class: Anthracyclines
Mech: Intercalate between DNA base pairs and donate electrons to O2 to form superoxide; superoxide reacts with itself to form H2O2 –> cleaved in the presence of Fe to form OH radical, which cleaves DNA
Thera: AML
Important SE’s: Irreversible dose-dependent cardiotoxicity; alopecia
Important SE’s: Myelosuppression (neutropenia), stomatitis, GI disturbances
Misc: Dexrazoxane is cardio-protective
Doxorubicin (Adriamicin, Doxil)
Class: Anthracyclines
Mech: Intercalate between DNA base pairs and donate electrons to O2 to form superoxide; superoxide reacts with itself to form H2O2 –> cleaved in the presence of Fe to form OH radical, which cleaves DNA
Thera: Sarcomas, breast and lung carcinomas, malignant lymphomas
Important SE’s: Irreversible dose-dependent cardiotoxicity; alopecia
Other SE’s: Myelosuppression (neutropenia), stomatitis, GI disturbances
Misc: Dexrazoxane can be used to prevent cardiotoxic effects
Epirubicin (Ellence)
Class: Anthracyclines
Mech: Intercalate between DNA base pairs and donate electrons to O2 to form superoxide; superoxide reacts with itself to form H2O2 –> cleaved in the presence of Fe to form OH radical, which cleaves DNA
Thera: Metastatic breast cancer, gastric cancer
Important SE’s: Irreversible dose-dependent cardiotoxicity; alopecia
Other SE’s: Myelosuppression (neutropenia), stomatitis, GI disturbances
Misc: Dexrazoxane can be used to prevent cardiotoxic effects
Bleomycin (Blenoxane)
Mech: Acts in G2 phase of cell cycle. Binds to DNA, producing ss- and dsDNA breaks
Thera: Combination therapy for testicular tumors or Hodgkin’s disease; squamous cell carcinomas and lymphomas
Important SE’s: Pulmonary toxicity (pulmonary fibrosis); cutaneous toxicity (hyperpigmentation, hyperkeratosis, erythema); hyperthermia
Other SE’s: Minimally myelo- and immunosuppressive (often used in combo therapy); headache, nausea, vomiting
Misc: Dexrazoxane can be used to prevent cardiotoxic effects
What are microtubule inhibitors in general?
Inhibit mitosis and cause metaphase arrest by interfering with microtubule function (tubulin (de)polymerization); CCS
Vinblastine (Velban)
Class: Vinca alkaloids
Mech: Block tubulin polymerization into microtubules
Thera: Metastatic testicular tumors (with bleomycin, cisplatin); component of ABVD used for Hodgkin’s disease
Other SE’s: Myelosuppression, nausea, vomiting
Vincristine (Oncovin)
Class: Vinca alkaloids
Mech: Block tubulin polymerization into microtubules
Thera: Childhood ALL (with glucocorticoids); Hodgkin’s and non-Hodgkin’s lymphomas
Important SE’s: Dose-limiting neurotoxicity (peripheral neuropathy)
Other SE’s: Relatively low bone marrow toxicity
Paclitaxel (Taxol, Abraxane)
Class: Taxanes
Mech: Block microtubule depolymerization into tubulin
Thera: Metastatic breast, ovarian, lung, and head and neck cancers
Important SE’s: Peripheral neuropathy
Other SE’s: Neutropenia; hypersensitivity reactions
How does Docetazel (Taxotere) compare with Paclitaxel?
Thera: Metastatic breast, ovarian, lung, and head and neck cancers; ALSO!! hormone refractory prostate cancer
What do topoisomerase inhibitors do?
Prevent the resealing of topo I (ssDNA) and topo II (dsDNA); CCS
Etoposide (Etopophos)
Class: Epipodophyllotoxins
Mech: Inhibits topoisomerase II
Thera: Testicular carcinoma, lung cancer, and non-Hodgkin’s lymphoma
Other SE’s: Dose-limiting myelosuppression (neutropenia), oral mucositis
Teniposide (Vumon): how is it different from etoposide?
Thera: ALL
Irinotecan (Camptosar)
Class: Camptothecin analogs
Mech: Inhibits topoisomerase I
Thera: Advanced colorectal cancer; lung, ovarian, cervical and brain tumors
Other SE’s: Severe neutropenia, severe diarrhea
How does topotecan (hycamtin) differ from irinotecan?
Thera: Ovarian and small cell lung cancer
What does hormone therapy attempt to target?
Treatment of hormone-dependent neoplasms
Prednisone (Meticorten)
Class: Glucocorticoids
Mech: Inhibit mitosis in lymphocytes
Thera: ALL; combination for Hodgkin’s, non-Hodkin’s, multiple myeloma, and CLL
How is dexamethasone different from prednisone?
Thera: Reduces edema in brain and spinal cord tumors with radiation therapy
Tamoxifen (Soltamox)
Class: Selective estrogen-receptor modulators (SERMs)
Mech: Competes with estradiol for binding to estrogen receptor
Thera: ER-positive breast cancer, or as adjuvant therapy following primary breast tumor excision; prevention of breast cancer in high-risk patients
Important SE’s: Hot flushes, hair loss; increased risk of endometrial cancer; increased risk of thromboembolic events
Other SE’s: Nausea and vomiting
Fulvestrant (Faslodex)
Class: Selective estrogen-receptor downregulators (SERDs)
Mech: Binds with much higher affinity (>100-fold) to estrogen receptor than tamoxifen, inhibiting dimerization, increasing degradation, and reducing overall ER levels
Thera: Posmenopausal women with ER-positive metastatic breast cancer
Aminoglutethamide (Cytadren)
Class: Aromatase inhibitors
Mech: Inhibits function of aromatase
Thera: Relatively weak, used against breast cancer
Important SE’s: Significant
Anastrozole (Arimidex)
Class: Aromatase inhibitors
Mech: Inhibits function of aromatase
Thera: First-line for ER-positive breast cancer in postmenopausal women
Letrozole (Femara)
Class: Aromatase inhibitors
Mech: Inhibits function of aromatase
Thera: ER-positive breast cancer in postmenopausal women
Exemestane (Aromasin)
Class: Aromatase inhibitors
Mech: Steroidal inhibitor of aromatase
Thera: ER-positive breast cancer in postmenopausal women
Leuprolide (Lupron)
Class: GnRH analogs
Mech: Binds GnRH receptor; inhibits release of FSH & LH
Thera: Androgen ablation therapy, along with AR blockers
How is goserelin (Zoladex) different relative to leuprolide?
IT’S NOT!!!
Flutamide (Eulexin)
Class: Nonsteroidal androgen-receptor blockers
Mech: Competes with androgen for AR binding
Thera: Androgen ablation therapy, along with GnRH analogs
Bicalutamide (Casodex)
See flutamide (eulexin)
Imatinib (Gleevac): misc
Class: Tyrosine Kinase inhibitor
Mech: Inhibits Abl kinase by binding where ATP should go; also inhibits PDGFR and c-kit; metabolized by cytochrome P450
Thera: First line therapy for CML; also, gastrointestinal tumor (GIST)
Important SE’s: Nausea and vomiting, fluid retention, muscle cramps, arthralgia
Other SE’s: Myelosuppression
Misc: Oral (1/day)
Gefitinib (Iressa)/ Erlotinib (Tarceva)
Class: Tyrosine Kinase inhibitor
Mech: Inhibit epidermal growth factor receptor (EGFR) tyrosine kinase
Thera: Non-small lung cancer
Nilotinib (Tasigna)
Class: Tyrosine Kinase inhibitor Mech: Inhibits Abl kinase Thera: Imatinib-resistant CML Important SE's: Myelosuppression Other SE's: QT prolongation, hepatotoxicity, electrolyte abnormalities Misc: Oral (2/day)
Dasatinib (Sprycel)
Class: Tyrosine Kinase inhibitor
Mech: Inhibits Abl & Src kinases
Thera: Imatinib-resistant CML
Important SE’s: Myelosuppression, bleeding, fluid retention, pulmonary arterial hypertension
Other SE’s: Diarrhea, nausea and vomiting, weakness, infections
Misc: Oral (1/day)
Rituximab (Rituxan)
Class: Monoclonal antibody
Mech: CD20 B-cell antibody that can directly activate apoptosis, activate complement, or activate cell-mediated cytotoxicity (e.g., T cells, NK cells)
Thera: Non-Hodgkin’s lymphomas
Important SE’s: Infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML)
Other SE’s: Skin reactions, irregular heartbeat, muscle or joint pain
Misc: Patients need careful monitoring
Trastuzumab (Herceptin)
Monoclonal antibody
Mech: Unknown HER2/neu (ErbB2) receptor antibody mechanism (enhanced receptor endocytosis or blocking homo- or heterodimerization)
Thera: HER2/neu-overexpressing metastatic breast cancer
Important SE’s: Hypersentivity reaction; ventricular dysfunction
Misc: Usually combined with taxanes; enhances doxorubicin cardiotoxicity
Cetuximab (Erbitux)
Class: Monoclonal antibody
Mech: EGFR1 (ErbB1)
Thera: EGFR-positive metastatic colorectal cancer
Important SE’s: Allergic reactions, sudden cardiac death, dermatologic problems, infections, renal failure, electrolyte abnormalities
Other SE’s: Asthenia/malaise, fever, nausea, constipation, interstitial pneumonitis
Misc: Clinical trials, probably combine with cisplatin
Ipilimumab (Yervoy)
Class: Human monoclonal antibody
Mech: Cytotoxic T-Lymphocyte Antigen 4 inhibitor; stimulates immune system
Thera: Melanoma
Hydroxyurea (Hydrea)
Mech: Inhibits ribonucleoside diphosphate reductase
Thera: CML (replaced by Imatinib), polycythemia vera, essential thrombocythemia; treatment for sickle cell disease (increases Hb-F)
Retinoids
Mech: ATRA induces terminal differentiation in malignant immature promyelocytes, which subsequently apoptose
Thera: APL
Important SE’s: “Leukocyte Activation Syndrome” (LAS), an increase in WBCs (fever, weight gain, respiratory distress, serosal effusion, renal failure)
Misc: Combined w/anthracyclines; corticosteroids used to block “LAS”
Arsenic Trioxide (Trisenox)
Thera: Relapsed APL
Thalidomide (Thalomid)
Thera: Multiple myeloma and myelodysplastic syndromes
Interferons
Thera: Hairy-cell leukemia, CML, and AIDS-related Kaposi’s sarcoma
