Hem-Onc Drugs

Front 1

Nitrogen mustards (5)

Back 1

Mechloroethamine
L-phenylalanine (L-PAM)
Chlorambucil
Cyclophosphamide
Bendamustine

Front 2

Nitrogen mustards: mechanism

Back 2

classic alkylating agents -
cross link DNA so it can't uncoil for replication

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Nitrogen mustards: adverse effects

Back 3

N/V
myelosuppression
hair loss
male sterility

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Cyclophosphamide: classification/MOA

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nitrogen mustard alkylating agent

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Cyclophosphamide: clinical use

Back 5

NHL

CLL

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Cyclophosphamide: toxicity

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HEMORRHAGIC CYSTITIS - give with fluids!!!

acrolein (metabolite) causes cystitis, myelosuppression, hair loss

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Nitrosureas: MOA

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indirect alkylating agent (requires activation in liver)

covalently cross-linkes DNA at guanine N-7

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Nitrosureas: clinical use

Back 8

brain tumors

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Nitrosureas: toxicity

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dizziness, ataxia

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Busulfan

MOA -
Clinical use -
Toxicity -

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Busulfan

alkylating agent
CML
pulmonary fibrosis, hyperpigmentation, myelosuppression

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Cisplatin: MOA

Back 11

acts like alkylating agent

identical platinum DNA-leaving group to carboplatin

Front 12

Cisplatin: clinical use

Back 12

testicular, bladder, ovary, lung CA

Front 13

Cisplatin: toxicity

Back 13

nephrotoxicity (give fluids!)
peripheral neuropathy
ototoxicity

*accumulation can sensitize pt to radiation

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Carboplatin:
MOA -
clinical use -

Back 14

alkylating agent-like
clinical use: same as cisplatin

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Carboplatin: toxicity

Back 15

nephrotoxicity
ototoxicity
dose-dependent TCP

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Carboplatin: dosing

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based on GFR

Front 17

L-phenyalanine (L-PAM)
MOA-
Clinical use -
toxicity -

Back 17

L-PAM
MOA: nitrogen mustard alkylating agent
Clinical use: multiple myeloma
Toxicity: N/V, myelosuppression, hair loss

Front 18

Anti-metabolites are all specific for which cell phase?

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S phase

Front 19

Which drug class are universally taken as prodrugs and activated in the body?

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antimetabolites

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Methotrexate: MOA

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folic acid analog, inhibits DHFR

Front 21

MTX: clinical use

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leukemias, lymphomas, sarcomas, chorioangiomas

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MTX: adverse effects

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myelosuppression (leucovorin rescue!)

fatty change in liver, mucositis, GI bleeds, desquamation

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6-mercaptopurine (6-MP): MOA

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blocks de novo purine synthesis
activated by HGPRTase

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6-MP
clinical use -
toxicity -

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6-MP:

ALL
follicular lymphoma

toxicity: BM, GI, liver
metabolized by xanthine oxidase - therefore, does must be lowered if patient is on allopurinol

Front 25

Which drug can lead to 6-MP toxicity?

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allopurinol

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5-fluorouracil (5-FU): MOA

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pyrimidine analog bioactivated to 5-FU-dUMP

binds thymidylate synthase --> decreased dTMP

same effect as MTX

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Substance that acts as a rescue drug for 5-FU

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thymidine

Front 28

5-FU
clinical use -
toxicity -

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5-FU

colon cancers, other solid tumors
synergy with MTX

toxicity: myelosuppression, photosensitivity

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Paclitaxel (Taxol)
MOA -
clinical use -
toxicity -

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Paclitaxel
MOA - inhibits microtubule disassembly so anaphase cannot occur

clinical use - breast, ovarian CA

toxicity - myelosuppression, hypersensitivity

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Vincristine
MOA -
clinical use -
toxicity -

Back 30

Vincristine
MOA - M-phase specific, blocks mitotic spindle formation

clinical use: lymphoma, leukemia, Wilm's tumor, choriocarcinoma

toxicity: neurotoxicity (areflexia, peripheral neuritis), tingling in fingers & toes, paralytic ileus

Front 31

Doxorubicin (Adriamycin)
MOA -
clinical use -
toxicity

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Doxorubicin
MOA - generates free radicals, inhibits topoisomerase II

clinical use - Hodgkin, myeloma, follicular lymphoma, breast, ovary, lung

toxicity - dose dependent CARDIOTOXICITY due to free radicals, myelosuppression, alopecia

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Bleomycin
MOA -
Clinical use -
toxicity -

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Bleomycin
MOA - DNA strand breaks

Clinical use - Hodgkin, NHL, testicular CA

Toxicity - pulmonary fibrosis, skin changes, MINIMAL myelosuppression

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L-asparaginase
MOA -
Clinical use -
Toxicity

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L-asparaginase
MOA - depletes asparagine, which leukemic cells cannot synthesize

Clinical use - ALL

Toxicity - fever, TCP

Front 34

Cushing-like symptoms caused by high-dose corticosteroids

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- immunosuppression
- cataracts
- acne
- osteoporosis
- hypertension
- peptic ulcers
- hyperglycemia

Front 35

Tamoxifen (or raloxifene)
MOA -
Clinical use -
Toxicity -

Back 35

inhibits estrogen binding to ER+ cancer cells - prophylactic use

breast cancer, osteoporosis

only toxic in POSTmenopausal women: increased risk uterine cancer, VTE, hot flashes

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Aminoglutethimide
MOA -
Clinical use -
Toxicity -

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Aminoglutethimide
MOA - blocks aromatase (androgens --> estrogens), blocks chl --> pregnenolone (lowers levels of all steroid hormones)

Clinical use - hormone sensitive BRCA

Toxicity - rash, hepatotoxicity, osteoporosis risk

Front 37

Exemestane
MOA
Clinical use
Toxicity

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Exemestane
aromatase inhibitor
breast cancer - postmenopausal women
toxicity: usu. well tolerated; myalgia, myarthralgia

Front 38

Anastozole
MOA
clinical use
toxicity

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Anastazole
MOA - aromatase inhibitor
breast cancer - post-menopausal women
toxicity: bone weakness (may want to use bisphosphonates)

Front 39

Letrozole
MOA
clinical use
toxicity

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Letrozole
MOA - nonsteroidal inhibitor of aromatase - specific to estrogen synthesis

clinical use - ER(+) breast cancers in post menopasual women only

toxicity: hot flashes, arthralgia, night sweats, osteoporosis risk

Front 40

Flutamide
MOA -
Clinical use -
toxicity -

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Flutamide
MOA - androgen receptor antagonist, nonsteroidal

clinical use - prostate cancer

toxicity - may induce gynomastia

Front 41

Leukovorin, aka ____, aka _____

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luekovorin, aka: citrovorum factor, aka: folinic acid

Front 42

Trastuzumab (Herceptin)
MOA
Clinical use
toxicity

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Trastuzumab
MOA - monoclonal Ab against HER2/Neu receptors

Clinical use - BRCA c/ HER2/Neu overexpression

Toxicity - CARDIOTOXICITY

Front 43

3 cancer drugs that cause cardiotoxicity

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Cyclophosphamide
Anthracyclines (Doxorubicin/Adriamycin)
Trastuzumab (Herceptin)

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What causes resistance to trastuzumab?

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IGF-1R activation

Front 45

Rituximab: MOA

Back 45

anti-CD20 monoclonal Ab:

Fc portion activates ADCC & complement pathway to kill B cells

Front 46

Rituximab: clinical use, toxicity

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Rituximab
clinical use: NHL, CLL, Follicular lymphoma, leukemias

toxicity: cardiac arrest, infusion reaction, infection

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Imatinib: MOA

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Philadelphia chromosome bcr-abl tyrosine kinase inhibitor;

blocks ATP pocket so signal is not transmitted

Front 48

Imatinib
clinical use:
toxicity:

Back 48

Imatinib:
use: CML
toxicity: edema

Front 49

Dasanitib
MOA:
Clinical use
Toxicity

Back 49

Dasanitib
2nd generation BCR-ABL inhibitor
Clinical use: CML & t(9;22)+ ALL
Toxicity: : neutropenia, myelosuppression, pleural effusion

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Bortezomib: MOA

Back 50

which targets proteins for degradation via polyubiquitination-thus bortezomib Reversibly inhibits the 26S proteasome (prevents proteolysis) --> prevents NF-κβ (anti-apoptotic factor) from translocating to nucleus and activating transcription

Front 51

Bortezomib
Clinical use
toxicity

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Bortezomib

multiple myeloma, mantle cell lymphoma (MCL)

peripheral neuropathy, myelosuppression, GI effects

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Thalidomide and Lenalidomide: MOA

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immunomodulators:
- anti-angiogenesis
- inhibits IL-6 production (myeloma cell GF)
- activates apoptotic pathway
- activates T-cells & increases IL-2 production
- augments activity of NK-dependent cytotoxicity

Front 53

Thalidomide and Lenalidomide:
clinical use
toxicity

Back 53

Thalidomide, Lenolidomide

clinical use: multiple myeloma

toxicity: Teratogenic, polyneuropathy, VTE

Front 54

Nevacizumab (Avastin): MOA

Back 54

anti-angiogenesis

humanized monoclonal Ab against VEGF (binds and prevents it from entering endothelial cells)

Front 55

Nevacizumab (Avastin):
clinical use
toxicity

Back 55

Nevacizumab

colorectal cancer

Toxicity: deadly VTE & strokes in 5% of patients

Front 56

Bisphosphonates (2)

Back 56

pamidronate
zoledronate

Front 57

Bisphosphonates
MOA
Clinical use
Toxicity

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Bisphosphonates
MOA - prevent osteoclast activity
Clinical use - multiple myeloma
Toxicity - musculoskeletal pain, upset stomach, osteonecrosis of jaw, renal dysfunction*

Front 58

Renal dysfunction for each bisphosphonate

Back 58

pamidronate - glomerulosclerosis/albuminuria (--> azotemia)

zoledronate - tubular dysfunction (no albuminuria)

Front 59

Cytarabine (ara-C)
MOA -
Clinical use -
Toxicity -

Back 59

Cytarabine
MOA: antimetabolite, inhibits DNA (and RNA) polymerase
- activated in vivo: Ara-C --> Ara-CMP --> Ara-CDP --> Ara-CTP (active)

Clincal use: AML
continuous infusion x7 days needed b/c of rapid degradation

Toxicity: cerebral damage, leukopenia, thrombocytopenia, megaloblastic anemia