Anti-neoplastic drugs Flashcards
-abine
cytosine analog (antimetabolite)
S phase active
-nib
kinase inhibitor
-platin
DNA damaging heavy metal (alkylating agent) bind N7 of guanine on single strand
-rubicin
anthracyclines (topo II directed agents)
-tecan
topo I directed agents
Dactinomycin
antibiotic
intercalates into DNA helix and inhibits RNA/protein synthesis
ADR: myelosuppression, nausea, mucositis, diarrhea, vesicant, radiation recall (skin reaction)
USE: pediatric cancers
Ado-trastuzumab emtansine
Anti-Her2 antibody conjugated with cytotoxin
ADR: cytopenias, liver damage, and cardiomyopathy (decreased EF)
alpha-interferon
cytokine
ADR: fever, chills, fatigue, cytopenias
USES: melanoma, myeloproliferative neoplasms
SAFE DURING PREGNANCY
Anastrazole
hormonal oncologic–> nonsteroidal (type II) cyp450 aromatase antagonist
acts in liver to prevent downstream production of estrogen
ADR: bone loss; fatigue
USE: breast cancer
Anti-metabolites are all active during which phase?
S phase
Arsenic Trioxide
generates free radicals–> cytotoxic
ADR: prolonged QT syndrome, hepatic, renal
USES: Acute promyelocytic leukemia
Azacytidine
antimetabolite (pyrimidine analog)
S phase active
cytosine analong; incorporation results in inhihibition of synthesis
hypomethylating agent which leads to increase in transcription
–> apoptosis
ADR: myelosuppression
metabolized by enzyme in tissue so useful for patients with hepatic or renal impairment
Bevacuzimab
Anti-VEGF antibody potentiates action of chemotherapy
ADR: bleeding/clotting, HTN, seizures/altered mental status, perforated viscus
Bleomycin
Antibiotic
produces free radicals and binds Fe–> damages DNA renal clearance
ADR: lungs and skin lack enzyme that clears bleomycin from tissue–> pulm and cutaneous toxicities fatal lung toxicity with high O2 (surgery risk) Raynaud’s syndrome, hypersensitivity
Use: hodgkin’s and germ cell cancers
Blinatumomab
Bispecific T cell engaging (BiTE) antibody against CD19 (on tumor cells) and CD3 (on T cells)–> acts as a bridge
ADR: cytokine release syndrome, neurotoxicity
Use: refractory B-precursor ALL
Bortezomib
proteasome inhibitor
ADR: thrombocytopenia, neuropathy, altered GI function
USES: Multiple myeloma
Brentuximab vedotin
Anti-CD30 antibody conjugated with cytotoxin
ADR: peripheral neuropathy, cytopenias, and upper respiratory symptoms
Carboplatin
Alkylating Agent–> DNA damaging heavy metal; crosslinks DNA
dose by AUC (patient’s renal function)
ADR: heme>>>>renal/neuro
Cetuximab
Anti-EGFR antibody–> blocks signaling and activates immune system
ADR: diarrhea, rash
Uses: Colon cancer (wt for ras); squamous head and neck cancer
Cisplatin
Alkylating Agent–> DNA damaging heavy metal; crosslinks DNA
requires hydration to avoid renal toxicity
ADR: renal > neuro/oto> heme
Common ADR of microtubule agents
myelosuppression, neuropathy
Cyclophosphamide
Alkylating Agent (Mustard)
PO
Prodrug- activated in liver
ADR: metabolites are toxic to bladder (high doses given with MESNA and hydration) high doses are cardiotoxic common- myelosuppression, alopecia, sterility, mucositis, carcinogenic, pulmonary fibrosis USES: non-hodgkin’s lymphoma
Cytarabine (Ara-C)
antimetabolite (pyrimidine analog)
S phase active
cytosine analog; inhibits synthesis –> apoptosis
ADR: myelosuppression, nausea, rash, mucositis, ocular irritation, and cerebellar toxicity at high doses
metabolized by enzyme in tissue so useful for patients with hepatic or renal impairment
USES: AML remission induction
Dacarbazine (DTIC)
Alkylating Agent–> alkylates O6 of guanine ADR: vomiting common- myelosuppression, alopecia, sterility, mucositis, carcinogenic, pulmonary fibrosis
Daunorubucin
Anthracycline–> Topo II inhibitor forms complex with DNA and Topo II and prevents re-ligation resulting in breaks in DNA –> apoptosis
ADR: interaction with radiation therapy common anthracycline- myelosuppression, vesicant, mucositis, GI, dose related cardiac toxicity
Decitabine
anti-metabolite (pyrimidine analog)
S phase active
cytosine analog; incorporation inhibits synthesis
hypomethylating agent resulting in increased transcription –> apoptosis
ADR: myleosuppression
metabolized by enzyme in tissue, so good for patients with hepatic or renal impairment
Doxorubicin
Anthracycline–> Topo II inhibitor forms complex with DNA and Topo II and prevents re-ligation resulting in breaks in DNA–> apoptosis
ADR: common anthracycline- mucositis, myelosuppression, vesicant, GI, dose related cardiac toxicity
Erlotinib
tyrosine kinase inhibitor
EGF-R
ADR: diarrhea, rash
Etoposide (VP-16)
Topo II inhibitor forms complex with DNA and Topo II and prevents re-ligation resulting in further breaks in DNA–> apoptosis
ADR: myelosuppression, alopecia reduce dose in proportion to creatinine clearance
Fluorouracil
antimetabolite (pyrimidine analg)
S phase active
inhibits thymidine synthesis by forming complex with folate and thymidylate synthase
ADR: myelosuppression, mucositis, CNS at high doses
Increased activity with Leucovorin
metabolized in tissue by DHPD, so good for patients with renal or hepatic dysfunction
Gemcitabine
Antimetabolite (pyrimidine analog)
S phase active
cytosine analog; inhibirs synthesis –> apoptosis
metabolized by enzyme in tissue, so useful for patients with hepatic and renal impairment
ADR: myelosuppression, “hand foot syndrome”
Goserelin
hormonal ongologic–> LHRH analog which results in disruption of normal pulsatile release and feedback mechanisms –> downregulation of testosterone and estrogen
ADR: bone pain, decreased sex drive
Hydroxyurea
USES: AML hyperleukocytosis
ADR: myelosuppression, mucositis
Idarubicin
Topo II inhibitor– anthracycline
complexes with DNA and Topo II to prevent re-ligation resulting in further DNA breaks–> apoptosis
less cardiotoxic than other anthracyclines
ADR: myelosuppression, vesicant, mucositis, GI
IL-2
cytokine–> induces T cell response, cytolytic for tumors
ADR: fever, chills, fatigue, cytopenias, infusion reactions with hypotension and vascular leak syndrome; altered mental status; cardiopulmonary
USES: high dose for metastatic renal tumors and melanoma
Imatinib
tyrosine kinase inhibitor
Bcr-abl, kit
ADR: fluid retention, hepatic, myelosuppression, rare cardiomyopathy
USES: CML, GIST
Ipilimumab
Anti-CTLA4–> stimulates immune system
ADR: infusion rxn (chills, fever, SOB, hypotension), exaggerated autoimmunity especially gut and hepatic dysfunction
Irinotecan (CPT 11)
Topo-I inhibitor
forms complex with DNA and Topo I, preventing re-ligation; breaks in DNA–> apoptosis Prodrug of SN38
Dose according to UGT allele status
ADR: myelosuppression, nausea, diarrhea (early and late onset), fatigue, alopecia
Letrozole
hormonal oncologic–> nonsteroidal (type II) cyp450 aromatase antagonist; acts in liver to prevent downstream production of estrogen
ADR: bone loss; musculoskeletal fatigue
USE: breast cancer
Leucovorin
Reduced folate
potentiates activity of 5-FU
rescue/protexts normal cells from methotrexate
Mechlorethamine
Alkylating Agent–> nitrogen mustard parent drug of class (chemical warfare)
ADR: blistering agent, vomiting common- myelosuppression, alopecia, sterility, mucositis, carcinogenic, pulmonary fibrosis
Melphalan
Alkylating Agent (Mustard)
PO
ADR: common- myelosuppression, alopecia, sterility, mucositis, carcinogenic, pulmonary fibrosis
Methotrexate
antimetabolite (folate antagonist)
S phase active
inhibits dihydrofolate reductase and thereby DNA synthesis
ADR: mucositis, myelosuppression, hepatic w/ chronic exposure
rescure/protect normal cell with Leucovorin
Renal clearance
Mitoxantrone
Topo II inhibitor
complexes with DNA and Topo II to prevent re-ligation resulting in further breaks in DNA–> apoptosis
less cardiotoxic than anthracycline
ADR: myelosuppression, mucositis, GI
Nivolumab
Anti- PD1 directed antibody
ADR: autoimmune like side effects including gut, hepatic, renal, thyroid
Ondansetron
type 3 serotonin antagonist
USES: nausea associated with chemo
Oxaliplatin
Alkylating Agent–> DNA damaging heavy metals; crosslinks DNA
ADR: neuro>>heme>>>>>renal
Paclitaxel
anti-microtubular agent
stabilizes tubules and prevents breakdown –> no progression to M phase
ADR: myelosuppression, neuropathy, vascular leak (=fluid retention), hypersentiviity to vehicle
Pembrolizumab
Anti-PD1 directed antibody
ADR: autoimmune like side effects including gut, hepatic, renal, thyroid
Prednisone
glucocorticoid receptor antagonist
ADR: glucocorticoid excess- hyperglycemia, fluid retention, gastric irritation, cushing’s syndrome, increased opportunitistic infections, myopathy, CNS changes
Procarbazine
Alkylating Agent
PO
crosses BBB
ADR: mood swings, somnolence common- myelosuppression, alopecia, sterility, mucositis, carcinogenic, pulmonary fibrosis
Rituximab
Anti-CD20 antibody–> inhibits lymphocyte signaling and activates immune response
ADR: infusion reaction (chills, fever, shortness of breath, hypotension)
Uses: B cell lymphomas
Romidepsin
Histone De-Acetylation (HDAC) Inhibitor
inhibits histone deacetylation –> apoptosis
ADR: cardiac, myelosuppression
Safe for pregnancy
Interferon Alpha
Sorafenib
tyrosine kinase inhibitor
VEGF-R, raf
ADR: HTN, proteinuria, rash, diarrhea, clotting/bleeding, hand-foot syndrome, rare hepatic
USES: Renal cell carcinoma
Sunitinib
tyrosine kinase inbihitor
VEGF-R, PDGF, kit
ADR: HTN, proteinuria, rash, clotting/bleeding, hand-foot syndrome, and rare hepatic
USES: Renal cell carcinoma
Tamoxifen
hormonal oncologic–> estrogen receptor antagonist; acts in cancer cell to prevent binding of estrogen to receptor
ADR: bone loss, thrombogenic, uterine neoplasms
Temozolomide
Alkylating Agent–> alkylates O6 of guanine
PO
crosses BBB
ADR: common- myelosuppresion, alopecia, sterility, mucositis, carcinogenic, pulmonary fibrosis
Toxicities common to alkylating agents
toxic to rapidly dividing cells–> myelosuppression, GI damage (mucositis), alopecia, impaired wound healing, impaired growth in children, immunosuppression, sterility, teratogenic, carcinogenic
Toxicities of anthracyclines
myelosuppression, vesicant, mucositis, GI, dose related cardiac toxicity
Trastuzumab
Anti-her2/neu antibody–> inhibits signaling (Herceptin)
ADR: cardiomyopathy (decrease EF), infusion reaction
Uses: Her2/neu + breast cancer (- hormone receptor)
Tretinoin (ATRA)
binds retinoic acid receptor
causes maturation of promyelocytes
ADR: teratogenic, increased intracranial pressure, cutaneous, hepatic, differentiation syndrome
USES: Acute promyelocytic leukemia t(15;17)
Vinblastine
Vinca alkaloid–> anti-microtubular agent
binds tubulin in M phase and blocks mitosis
ADR: myelosuppression; neuropathy
(in ABVD)
Vincristine
vinca alkaloid–> anti-microtubular agent
binds tubulin in M phase and blocks mitosis
ADR: neuropathy > myelosuppression
CAR
recognizes antigen on cancer cell, independent of MHCI
ADR: cytokine release syndrome (treat with antibody to IL-6)
USES: ALL
ABVD
A= Adriamycin= doxorubicin
B= bleomycin
V= vinblastine
D= dacarbazine
Hand Foot Syndrome
Gemcitabine
Cerebellar toxicity at high doses
Cytarabine
Uterine neoplasms
Tamoxifen
Prolonged QT
arsenic trioxide
Dosed according to UGT allele status (b/c of myelosuppression)
Irinotecan
Less cardiogenic anthracycline
mitoxantrone
Useful for patients with hepatic/renal impairment
cytosine analogs
fluorouracil
3 Drugs that are anti-VEGF
Sunitinib
Sorafenib
Bevacizumab
Asparaginase
treatment of ALL
ADR: thrombosis, pancreatitis
refractory B cell ALL
blinatumomab
major side effect of ATRA and treatment
differentiation syndrome- fever, pleural effusions, pericardial effusions, hypotension, etc.
dexamethasone
2 cycles of diarrhea
irinotecan
