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Onco Flashcards

1
Q

Carboplatin

A

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

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2
Q

Cisplatin

A

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

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3
Q

Cyclophosphamide

A

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

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4
Q

Dacarbazine

A

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

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5
Q

Melphalan

A

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

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6
Q

Mechlorethamine

A

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

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7
Q

Oxaliplatin

A

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

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8
Q

Procarbazine

A 
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
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9
Q

Temozolomide

A

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

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10
Q

Bleomycin

A

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

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11
Q

Dactinomycin

A 
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
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12
Q

Daunorubicin

A 
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
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13
Q

Doxorubicin

A 
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
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14
Q

Etoposide

A 
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
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15
Q

Mitoxantrone

A

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

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16
Q

Idarubicin

A 
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
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17
Q

Bevacuzimab

A 
Antibody antineoplastic agent
Anti-VEGF
- prevents angiogenesis
Use: tumors expressing VEGF
Toxicity:
- hypertension
- clotting
- bleeding
- perforation of viscus
- CNS dysfnx
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18
Q

Cetuximab

A 
Antibody antineoplastic agent
Anti-EGFR
- blocks immune activation 
Use: colon, head and neck cancer
Toxicity
- infusion rxn - fever, chills, hypotension, bronchospasm
- cutaneous - rash
- diarrhea
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19
Q

Rituximab

A

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

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20
Q

Trastuzumab

A

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

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21
Q

Blinatumomab

A

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

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22
Q

Ado-trastuzumab emtansine

A 
Antibody antineoplastic agent
Anti-Her2 
Toxicity:
- cytopenia
- liver damage
- heart failure
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23
Q

Ipilimumab

A 
Antibody antineoplastic agent
Anti-CTLA4
CTLA4 is a negative signal to T cell activation (like PD1)
Use: melanoma
Toxicity:
- autoimmune: gut, hepatic
- renal, thyroid
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24
Q

Brentuximab vedotin

A

Antibody antineoplastic agent
Conjugated antibody - has cytotoxic molecule attached
Anti-CD30 (on Reed Sternberg cells)
Use: Hodgkin’s lymphoma

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25
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 ```
26
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 ```
27
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
28
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
29
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
30
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
31
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
32
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
33
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 ```
34
Vinblastine
``` Anti-microtubular antineoplastic agent Mitotic inhibitor Vinca Alkaloid Mechanism: - disassemble microtubules Toxicity: - myelosuppression - more myelo than neuro - neuropathy - fluid retention - due to vehicle ```
35
Vincristine
``` Anti-microtubular antineoplastic agent Mitotic inhibitor Vinca Alkaloid Mechanism: - disassemble microtubules Toxicity: - myelosuppression - neuropathy - more neuro than myelo - fluid retention - due to vehicle ```
36
Erythropoietin
Growth/CS factor antineoplastic agent Toxicity: - clotting - may promote tumor growth
37
Sargramostim
``` Growth/CS factor antineoplastic agent Toxicity: - high incidence of fever - chills - bone pain - exacerbate inflammatory states ```
38
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
39
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 ```
40
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
41
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 ```
42
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 ```
43
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 ```
44
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 ```
45
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
46
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
47
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
48
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 ```
49
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 ```
50
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
51
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 ```
52
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 ```
53
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 ```
54
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
55
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) ```
56
Cis-retinoic acid (?)
Hematologic antineoplastic agent
57
GCSF (? same as Sargramostim)
Growth factor antineoplastic agent
58
Ondansetron (?)
Anti-emetic therapy
59
Cirzotinib/Xalkori (?)
Anti-ALK | anaplastic lymphoma kinase
60
Imid
``` Thalidomide, Lenalidomide - alter cytokine milieu Immunomodulator Use: multiple myeloma Toxicity: - thromboses - cytopenias ```
61
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
62
Alkylating agents
``` Platinum derivatives: - Oxiplatin, Carboplatin, Cisplatin Cyclophosphamide Dacarbazine Melphalan Mechlorethamine Procarbazine Temozolomide ```
63
Antibiotics
Bleomycin | Dactinomycin
64
Topo II inhibitors
``` Daunorubicin Doxorubicin Etoposide Mitoxantrone Idarubicin ```
65
Antibodies
``` Bevacuzimab Cetuximab Rituximab Trastuzumab Blinatumomab Ado-trastuzumab emtansine Ipilimumab Bretuximab Pembrolizumab Nivolumab ```
66
Anti-metabolites
``` Decitabine Azacitidine Cytarabine Fluorouracil Gemciabine Methotrexate ```
67
Anti-microtubule
Paclitaxel Vinblastine Vincristine
68
Growth/CS factors
Erythropoietin | Samgramostim
69
HDAC inhibitor
Romidepsin
70
Hormonal oncologics
``` Anastrazole Goserelin Letrozole Prednisone Tamoxifen ```
71
Topo I inhibitors
Irinotecan
72
Tyrosine kinase inhibitors
Erlotinib Imatinib Sorafenib Sunitinib
73
Other oncologics
Hydroxyurea
74
Antidote to folic acid antagonists
Leucovorin
75
Additional hematologics
Arsenic trioxide IL-2 IFN-a Tretinoin - all trans retinoic acid
76
Anti-emetic therapy
Ondansetron

Therapeutic Drugs (7 decks)

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