Onco Flashcards
Carboplatin
Alkylating antineoplastic agent
Platinum derivative
Mechanism:
- bind N7 of guanine on single strand, cross links DNA
- binds NH2 or SH groups on proteins
Dosed according to pt renal fnx (AUC), doesn’t cause renal dysfnx
Toxicity:
- hematopoietic toxicity mostly, less toxic to kidney and neuro
Cisplatin
Alkylating antineoplastic agent
Platinum derivative
Mechanism:
- bind N7 of guanine on single strand, cross links DNA
- binds NH2 or SH groups on proteins
Requires hydration otherwise get renal damage
Toxicity:
- renal toxicity mostly, less neuro toxic
- ototoxicity
Cyclophosphamide
Alkylating antineoplastic agent
Mustard
Prodrug - requires hepatic activation - modify dose based on LFTs
Toxicity:
- alkylating common: myelosuppression, mucositis, alopecia, impaired wound healing, impaired growth in children, reduced resistance to infxn, nausea/vomit, sterility, TERATOGENIC, carcinogenic
- leukopenia and thrombocytopenia; recovers in about 20 days
- mucositis
- bladder toxic in high or prolonged oral dosing; give MESNA with hydration to protect bladder
- high doses - cardiotoxicity, SIADH, lung toxicity
Dacarbazine
Alkylating antineoplastic agent
Emetogenic
Toxicity:
- alkylating common: myelosuppression, mucositis, alopecia, impaired wound healing, impaired growth in children, reduced resistance to infxn, nausea/vomit, sterility, TERATOGENIC, carcinogenic
Melphalan
Alkylating antineoplastic agent
Mustard
Toxicity:
- alkylating common: myelosuppression, mucositis, alopecia, impaired wound healing, impaired growth in children, reduced resistance to infxn, nausea/vomit, sterility, TERATOGENIC, carcinogenic
Mechlorethamine
Alkylating antineoplastic agent
Nitrogen Mustard
Toxicity:
- alkylating common: myelosuppression, mucositis, alopecia, impaired wound healing, impaired growth in children, reduced resistance to infxn, nausea/vomit, sterility, TERATOGENIC, carcinogenic
- leukopenia and thrombocytopenia, recover after 20 days
- vesicant
- emetogenic
Oxaliplatin
Alkylating antineoplastic agent
Platinum derivative
Mechanism:
- bind N7 of guanine on single strand, cross links DNA
- binds NH2 or SH groups on proteins
Toxicity:
- mostly neurotoxic, little renal toxicity
Procarbazine
Alkylating antineoplastic agent Oral bioavailability CNS penetration Hodgkin's lymphoma use use in gliomas/brain tumors Toxicity: - CNS toxicity: somnolence, mood swings - alkylating common: myelosuppression, mucositis, alopecia, impaired wound healing, impaired growth in children, reduced resistance to infxn, nausea/vomit, sterility, TERATOGENIC, carcinogenic
Temozolomide
Alkylating antineoplastic agent
Alkylate O6 position of guanine - distinct repair pathway
Alkylguanine alkyl transfer - low leves are a predictive marker
Use in glioma
Toxicity
- alkylating common: myelosuppression, mucositis, alopecia, impaired wound healing, impaired growth in children, reduced resistance to infxn, nausea/vomit, sterility, TERATOGENIC, carcinogenic
Bleomycin
Antibiotic antineoplastic agent
Binds iron - produces free radicals that damage DNA
Toxicity increased by presence of O2
Renal clearance - reduce dose in renal dysfnx
Toxicity:
- pulmonary and cutaneous, especially with decreased renal fnx - increased toxicity with cumulative dose; underlying pulmonary disease and radiation make this worse
- persists in lungs fatal activation of lung toxicity during surgery with high O2
- raynaud’s phenomenon
For Hodgkins and Germ cell
Dactinomycin
Antibiotic antineoplastic agent Intercalate into DNA helix - inhibit RNA and protein synthesis Use in pediatric neoplasm regimens Toxicity: - myelosuppression - mucositis - diarrhea - nausea/vomit - vesicant - damages skin if gets outside the vein - avoid extravasation - radiation recall
Daunorubicin
Topo II inhibitor antineoplastic agent - topo II makes double strand break, drug binds and stabilizes Anthracycline Radiation sensitive Elimination by liver Toxicity: - myelosuppression - mucositis - alopecia - cardiac toxicity - due to free radical generation - vesicant - extravasation damage
Doxorubicin
Topo II inhibitor antineoplastic agent - topo II makes double strand break, drug binds and stabilizes Anthracycline Radiation sensitive Elimination by liver Toxicity: - myelosuppression - mucositis - alopecia - cardiac toxicity - due to free radical generation - vesicant - extravasation damage
Etoposide
Topo II inhibitor antineoplastic agent - topo II makes double strand break, drug binds and stabilizes Reduce dose with creatinine clearance Used in lung cancers Toxicity: - neutropenia, thrombocytopenia - alopecia - not much end organ damage
Mitoxantrone
Topo II inhibitor antineoplastic agent
- topo II makes double strand break, drug binds and stabilizes
Less cardiotoxic and less emetogenic than anthracyclines
Toxicity:
- myelosuppression, mucositis, GI
Idarubicin
Topo II inhibitor antineoplastic agent - topo II makes double strand break, drug binds and stabilizes Anthracycline Radiation sensitive Elimination by liver Toxicity: - less cardio-toxic than the others on a weight basis - preferred in adults - myelosuppression - mucositis - alopecia - cardiac toxicity - due to free radical generation - vesicant - extravasation damage
Bevacuzimab
Antibody antineoplastic agent Anti-VEGF - prevents angiogenesis Use: tumors expressing VEGF Toxicity: - hypertension - clotting - bleeding - perforation of viscus - CNS dysfnx
Cetuximab
Antibody antineoplastic agent Anti-EGFR - blocks immune activation Use: colon, head and neck cancer Toxicity - infusion rxn - fever, chills, hypotension, bronchospasm - cutaneous - rash - diarrhea
Rituximab
Antibody antineoplastic agent
Anti-CD20
- blocks CD20 on B cells, inhibit lymphocyte signaling and immune activation
Use: non-Hodgkin’s lymphoma
Toxicity:
- infusion rxn - fever, chills, SOB, hypotension
Trastuzumab
Antibody antineoplastic agent
Anti-Her2/neu
- inhibits signaling and immune activation
Use: Her2 positive breast cancer
Toxicity:
- infusion rxn - fever, chills, SOB, hypotension
- cardiomyopathy - decreased EF
Blinatumomab
Antibody antineoplastic agent
Conjugated antibody
Bi-specific T cell engager for CD3 and CD19 BiTE
- bridges T cells and tumor B cells in ALL
Toxicity:
- cytokine release syndrome
- neurotoxicity
Ado-trastuzumab emtansine
Antibody antineoplastic agent Anti-Her2 Toxicity: - cytopenia - liver damage - heart failure
Ipilimumab
Antibody antineoplastic agent Anti-CTLA4 CTLA4 is a negative signal to T cell activation (like PD1) Use: melanoma Toxicity: - autoimmune: gut, hepatic - renal, thyroid
Brentuximab vedotin
Antibody antineoplastic agent
Conjugated antibody - has cytotoxic molecule attached
Anti-CD30 (on Reed Sternberg cells)
Use: Hodgkin’s lymphoma
Pembrolizumab
Antibody antineoplastic agent Anti-PD1 receptor PD1 - tumor antigen that makes cancer cells invisible to immune system Use: melanoma Toxicity: - auto-immune: gut, hepatic - renal, thyroid
Nivolumab
Antibody antineoplastic agent Anti-PD1 receptor PD1 - tumor antigen that makes cancer cells invisible to immune system Use: melanoma Toxicity: - auto-immune: gut, hepatic - renal, thyroid
Decitabine
Antimetabolite antineoplastic agent
DNA hypomethylating agent (methylation silences genes, increased in tumorigenesis)
Nucleoside
Mechanism:
- incorporation into DNA leads to inactivation of DNA methyl transferase - alters gene expression
Not orally bioavailable
Use: sickle cell anemia, acute myeloid leukemia, myelodysplastic syndrome
Toxicity:
- myelosuppression
Azacytidine
Antimetabolite antineoplastic agent
DNA hypomethylating agent (methylation silences genes, increased in tumorigenesis)
Nucleoside
Mechanism:
- incorporation into DNA leads to inactivation of DNA methyl transferase - alters gene expression
Not orally bioavailable
Use: sickle cell anemia, acute myeloid leukemia, myelodysplastic syndrome
Toxicity:
- myelosuppression
Cytarabine
Antimetabolite antineoplastic agent
- S phase active, get incorporated into DNA/RNA and result in cell death - inhibit normal nucleotide synthesis
Inhibits DNA synth from deoxyribonucleotides
Cytosine analog
Metabolized by cytidine deaminase - useful in hepatic and renal dysfnx
Toxicity:
- myelosuppression especially with continuous IV
- hand foot
- eye irritation
- cerebellar
Fluorouracil
Antimetabolite antineoplastic agent
- S phase active, get incorporated into DNA/RNA and result in cell death - inhibit normal nucleotide synthesis
Inhibits DNA synth from deoxyribonucleotides
Mechanism:
- inhibit thymidine synthesis, forms covalent complex with folate and thymidylate synthase
Useful in hepatic and renal impairment
Enhance activity by giving leucovorin with 5FU
Metabolized by dihydropyrimidine dehydrogenase; if DHPD deficiency, severe toxicity - rescue via uridine
Toxicity:
- myelosuppression
- GI
- cerebellar and neurocognitive at high doses
- coronary spasms - rare
Gemcitabine
Antimetabolite antineoplastic agent
- S phase active, get incorporated into DNA/RNA and result in cell death - inhibit normal nucleotide synthesis
Cytosine analog
Metabolized by cytidine deaminase - useful in hepatic and renal dysfnx
Toxicity:
- myelosuppression especially with continuous IV
- hand foot prominent
- eye irritation
- cerebellar
Methotrexate
Antimetabolite antineoplastic agent
- S phase active, get incorporated into DNA/RNA and result in cell death - inhibit normal nucleotide synthesis
Inhibits ribonucleotide synthesis from purines at high doses
Inhibits DNA synth from deoxyribonucleotides at all doses
Mechanism:
- inhibits dihydrofolate reductase, blocking DNA/RNA precursor formation
Toxicity:
- myelosupprsion
- mucositis
- hepatic toxicity in chronic exposure
- pulmonary fibrosis/interstitial lung disease
If giving high dose - use leucovorin and hydration/alkalinize urine
Paclitaxel
Anti-microtubular antineoplastic agent Microtubule polymer stabilizer Taxane Mechanism: - stabilize microtubules, but they are abnormal and poorly functional Toxicity: - myelosuppression - neuropathy - fluid retention - due to vehicle - taxane specific: fluid retention/vascular leak; hypersensitivity rxn to vehicle
Vinblastine
Anti-microtubular antineoplastic agent Mitotic inhibitor Vinca Alkaloid Mechanism: - disassemble microtubules Toxicity: - myelosuppression - more myelo than neuro - neuropathy - fluid retention - due to vehicle
Vincristine
Anti-microtubular antineoplastic agent Mitotic inhibitor Vinca Alkaloid Mechanism: - disassemble microtubules Toxicity: - myelosuppression - neuropathy - more neuro than myelo - fluid retention - due to vehicle
Erythropoietin
Growth/CS factor antineoplastic agent
Toxicity:
- clotting
- may promote tumor growth
Sargramostim
Growth/CS factor antineoplastic agent Toxicity: - high incidence of fever - chills - bone pain - exacerbate inflammatory states
Romidepsin
Histone De-Acetylase inhibitor antineoplastic agent
Mechanism:
- blocks HDAC which would normally silence transcription; downregulates genes associated with growth, upregulates genes associated with inhibition of cell proliferation, leads to differentiated fnxs
Use: Cutaneous T cell Lymphoma
Toxicity:
- cardiac
- myelosuppression
Anastrazole (Arimidex)
Hormonal oncologic antineoplastic agent Aromatase inhibitor Type II - nonsteroidal Mechanism: - blocks estrogen synthesis at cyp450 aromatase Use: - breast/endometrial cancer Toxicity: - bone loss - fatigue
Goserelin
Hormonal oncologic antineoplastic agent
LHRH analog
Mechanism:
- hypothalamic stimulator of continuous LH release therefore lose normal pulsatile release and decrease net LH release
- therefore decrease testosterone production
Letrozole
Hormonal oncologic antineoplastic agent Aromatase inhibitor Type II - nonsteroidal Mechanism: - blocks estrogen synthesis at cyp450 aromatase Use: - breast/endometrial cancer Toxicity: - bone loss - MSK fatigue
Prednisone
Hormonal oncologic antineoplastic agent Mechanism: - induce apoptosis via glucocorticoid receptor action Use: - leukemia Toxicity (related to glucocorticoid excess): - hyperglycemia - fluid retention - gastric irritation - Cushing's syndrome - myopathy - CNS changes - increased opportunistic infxns
Tamoxifen
Hormonal oncologic antineoplastic agent Anti-estrogen Mechanism: - blocks estrogen receptor, estradoil cannot bind ER Toxicity: - bone loss - thrombogenic with DVT and large organ thromboses - uterine neoplasms
Irinotecan
Topo I inhibitor antineoplastic agent - topo I makes single strand break Prodrug of SN38 - made in liver Toxicity: - diarrhea: early onset - atropine sensitive; late onset - reflects clearance of SN38 - myelosuppression - alopecia - nausea/vomit - fatigue
Erlotinib
Tyrosine kinase inhibitor antineoplastic agent
Target: EGF receptor
Use: non-small cell lung cancer and pancreatic
More specific binding to kinase has more specific inhibitor action
Toxicity:
- cutaneous - rash
- GI - diarrhea
Imatinib
Tyrosine kinase inhibitor antineoplastic agent
Target: p210bcr-abl, kit
Use: chronic myelogenous leukemia with bcr-abl
More specific binding to kinase has more specific inhibitor action
Toxicity:
- cytopenias
- liver abnormalities
- fluid retention
- rare cardiomyopathy
Sorafenib
Tyrosine kinase inhibitor antineoplastic agent
Multikinase antagonist
Targets: VEGF receptor, raf (FLT3)
Use: renal cell and hepatocellular carcinoma
More specific binding to kinase has more specific inhibitor action
Toxicity - related to vascular system:
- hypertension
- proteinuria
- perforated viscus (spontaneous)
- clotting/bleeding
- hand/foot syndrome due to extravasation
- rash
- diarrhea
Sunitinib
Tyrosine kinase inhibitor antineoplastic agent Multikinase antagonist Targets: VEGF receptor, PDGF, kit (FLT3) Use: renal cell carcinoma More specific binding to kinase has more specific inhibitor action Toxicity - related to vascular system: - hypertension - proteinuria - perforated viscus (spontaneous) - clotting/bleeding - hand/foot syndrome due to extravasation - rash - diarrhea
Hydroxyurea
Oncologic antineoplastic agent DNA directed agent Orally bioavailable Mechanism: - reversible inhibition of ribonucleotide reductase by chelation of non-heme iron at reactive center - decreases dNTP pools, stalls replication Toxicity: - myelosuppression - mucosal damage - enhanced effect in renal failure
Leucovorin
Antidote to folic acid antagonists
- reduced folate, does not require dihydrofolate reductase for action
- rescues normal cells, loads cancer cells with MTX
- also used to enhance 5FU toxicity to cancer cells
Arsenic trioxide
Hematologic antineoplastic agent Use: Acute Promyelocytic Leukemia Mechanism: - receives and donates electrons, generates free radicals Toxicity: - heavy metal toxicity - kidney, hepatic - cardiac conduction problems - long QT
IL-2
Hematologic antineoplastic agent Induces T cell response - cytolytic to tumors Use: melaoma, renal cell carcinoma Toxicity: - hypotension, vascular leak - headache/fever/chills/fatigue (flu-like) - altered mental status - cardiopulmonary
alpha-interferon
Hematologic antineoplastic agent Biological response modifier Use: adjuvant for melanoma; myeloproliferative neoplasms (CML); Kaposi's sarcoma Safe in pregnancy Toxicity: - fatigue, fever, chills (flu-like) - cytopenias - hypotension due to vascular leak - chronic use: depression
Tretinoin (all-trans retinoic acid)
Hematologic antineoplastic agent
Mechanism:
- binds retinoic acid receptor, induces differentiation of leukemic cells
Use: Acute Promyelotic Leukemia with 15;17 translocation
Toxicity:
- teratogenic
- cutaneous - dry skin, ocular keratitis
- increased intracranial pressure - headaches, papilledema
- differentiation syndrome - differentiated tumor cells release cytokines in tissues and cause organ damage
Bortezomib
Proteosome inhbitor antineoplastic agent Mechanism: - Block digestion of proteins targeted for degradation, prevents cytokine action that would occur through NF-kB Use: multiple myeloma and lymphoma Toxicity: - neuropathy - thrombocytopenia - altered GI fnx - cardio and pulmonary toxicity (prominent)
Cis-retinoic acid (?)
Hematologic antineoplastic agent
GCSF (? same as Sargramostim)
Growth factor antineoplastic agent
Ondansetron (?)
Anti-emetic therapy
Cirzotinib/Xalkori (?)
Anti-ALK
anaplastic lymphoma kinase
Imid
Thalidomide, Lenalidomide - alter cytokine milieu Immunomodulator Use: multiple myeloma Toxicity: - thromboses - cytopenias
CAR-T
Genetically modified T cell - given new genes that allow production of a TCR that does not need MHC
- has internal region that acts as a co-stim
- grow up the T cells with IL-2 before giving back to host
Mechanism:
- allow for non-MHC recognition of tumor antigen
Toxicity:
- cytokine release syndrome
Alkylating agents
Platinum derivatives: - Oxiplatin, Carboplatin, Cisplatin Cyclophosphamide Dacarbazine Melphalan Mechlorethamine Procarbazine Temozolomide
Antibiotics
Bleomycin
Dactinomycin
Topo II inhibitors
Daunorubicin Doxorubicin Etoposide Mitoxantrone Idarubicin
Antibodies
Bevacuzimab Cetuximab Rituximab Trastuzumab Blinatumomab Ado-trastuzumab emtansine Ipilimumab Bretuximab Pembrolizumab Nivolumab
Anti-metabolites
Decitabine Azacitidine Cytarabine Fluorouracil Gemciabine Methotrexate
Anti-microtubule
Paclitaxel
Vinblastine
Vincristine
Growth/CS factors
Erythropoietin
Samgramostim
HDAC inhibitor
Romidepsin
Hormonal oncologics
Anastrazole Goserelin Letrozole Prednisone Tamoxifen
Topo I inhibitors
Irinotecan
Tyrosine kinase inhibitors
Erlotinib
Imatinib
Sorafenib
Sunitinib
Other oncologics
Hydroxyurea
Antidote to folic acid antagonists
Leucovorin
Additional hematologics
Arsenic trioxide
IL-2
IFN-a
Tretinoin - all trans retinoic acid
Anti-emetic therapy
Ondansetron
