Monday 1 - fitz - Antineoplastics

Question 1

Vincristine

other name
used in what combinations for what disease

Answer 1

Onvcovin

MOPP for Hodgkin’s disease
CHOP for non-Hodgkin’s lymphoma

Question 2

vinblastine

used in what combination for what disease

Answer 2

ABVD for Hodgkin’s disease

PVB for testicular cancer

Question 3

toxicity of vincristine vs vinblastine

toxicity of both

Answer 3

vinCristine - more CNS tox (fatal if intrathecal)

vinBlastine - more Bone marrow suppression

vesicant, alopecia, depression of deep tendon reflexes within 2-3 weeks in 100% of patients (this sign is used to tell that its working)

Question 4

Taxanes

Answer 4

capazitaxel, docataxel, paclitaxel

stabilize tubulin, too much spindle activity
pumped out by p-glycoprotein

hypersensitivity RXN can occur, new forms of paclitaxel are albumin bound and cause less of this4peripheral neuropathy

Question 5

Ixabepilone

main points,
3rd line Tx for what

Answer 5

enhances stability of tubules, like paclitaxel but it is an antibiotic

DOESN’T produce a multidrug resistant tumor, like most other natural products do (via upregulation of P-glycoprotein)

used with capecitabine to Tx breast cancer (third line Tx)

Question 6

DEXAMETHASONE, PREDNISONE

Answer 6

Glucocorticoids, immunosuppressants

treatment of cancers that express the requisite receptors

Question 7

CYCLOSPORINE, TACROLIMUS

Answer 7

Antibiotics, mTOR inhibitors. immunosuppressants

used to prevent rejection following bone marrow transplants

CYCLOSPORINEbinds tocyclophilin, inhibitscalcineurin, stops NFAT, which usually helps produce IL-2

TACROLIMUSbinds toFK-binding protein, inhibitscalcineurin, stops NFAT

Question 8

EVERLOLIMUS, TEMSIROLIMUS)

Answer 8

Antibiotics, mTOR inhibitors . immunosuppressants, angiogenesis inhibitor

mTOR upregulates cell growth and angiogenesis, and regulates the synthesis of D1

Question 9

ALEMTUZUMAB

Answer 9

antibody mimmunosuppressant\

used for specific leukemia and lymphomas because they target unique CDs

targets CD52

Specific SE: cough, tightness in chest

Question 10

DENILEUKIN DIFTITUX

Answer 10

fusion protein immunosuppressant

used for specific leukemia and lymphomas because they target unique CDs

diphtheria toxin coupled to IL-2

diphtheria toxin catalyzes the ADP-ribosylation of elongation factor-2inhibits protein translationby inactivating EF2

Question 11

IBRITUMOMAB

Answer 11

antibody
immunosuppressant\

used for specific leukemia and lymphomas because they target unique CDs

targets CD20

may be more likely to cause birth defects

Question 12

RITUXIMAB

Answer 12

antibody
immunosuppressant

used for specific leukemia and lymphomas because they target unique CDs

targets cd20

Question 13

TOSITUMOMAB

Answer 13

antibody
immunosuppressant

used for specific leukemia and lymphomas because they target unique CDs

targets CD20

may be more likely to cause birth defects

Question 14

Mechanism of immunosuppressive antibiotics

Answer 14

immunosuppressive antibiotics interfere with intracellular processes that are key for cell proliferation and cytokine production and release
the 1st step in the process that leads to IL-2 mediated cell proliferation is activation ofreceptor tyrosine kinases (RTKs)
immunosuppressive antibiotics do not interfere with this process; they interfere with one of two intracellular signaling cascades

Question 15

calcineurin

Answer 15

necessary for activation of NFAT, a T cell-specific transcription factor that is involved in the synthesis of interleukins by activated T cells

If we have decreased cacimurin then we get decreased releaseofIL-2→decreased activation of IL-2 receptor → decreased cell proliferation

Cyclosporine and tacrolimus inhibit this

Question 16

Do a mantoux test before giving what for cancer

Answer 16

anthing anti immune, esp antibodies apparently

Question 17

Toxicities of anti CD antibodies

Answer 17

cardiac arrhythmias

tumour lysis syndrome

Question 18

INTERLEUKIN 2

side effects of high doses:

Answer 18

activation and expansion of lytic lymphocytes causes inflammation, vascular leak and secondary release of other cytokines (such as TNF, interferon α) = cytokine storm

can produce mild/moderate symptoms such as fever/chills, diarrhea and weight gain or hand-foot syndrome (palmar-plantar erythrodysesthesia)

serious toxicities such as thrombocytopenia, shock, respiratory distress, coma andfatal hypotension

Question 19

INTERFERON α

three mechanisms of anti-tumour activity

unique SE

Answer 19

decreasesthe production offibroblast growth factor (FGF)
anti-FGF actions may be responsible for actions against leukemic stem cells inchronic myeloid leukemia
FGF isangiogenic
inhibition of cell division of both normal and tumour cells
increases class I MHC expression on tumour cells(actually restores normal MHC expression levels>increased activity of cytotoxic T lymphocytes)

SE: depression

Question 20

TUMOUR NECROSIS FACTOR α

Answer 20

similar to IL-1 in terms of actions: causes fibroblast proliferation, chemokine induction (IL-6, IL-8), T and B cell activation
effects on many cell types (at least 17 different kinds) - causes a decrease in the rate of proliferation of tumour cells while sparing normal cells
intra-arterial administrationdue to extremely short half-life and toxicity
severe dose-limiting toxicity ismalaise and flu-like symptoms- can cause hemorrhagic necrosis

Question 21

Erythropoietin

Answer 21

makes RBCs

Question 22

Filgrastim (g-csf)

Answer 22

makes neutrophils

Question 23

Sargramostim (gm-csf

Answer 23

Makes Granulocytes, eosinophils, basophils, monocytes

Question 24

Interleukin 11

Answer 24

makes platelets

Question 25

Thrombopoietin

Answer 25

makes platelets

Question 26

PDGF-R, VEGF-R, and VEGF inhibitors of tyrosine kinase

Answer 26

Bevacizumab (VEGF) - first line treatment, can be used for glioblastoma,

STIs: PAZOPANIB, SORAFENIB, SUNITINIB (VEGF-R) - these are not as specific in which kinases they inhibit - first line Tx for renal cell carcinoma

Very expensive

Question 27

Tyrosine kinase inhibitors - inhibitors of EGFR

Answer 27

Cetuximab, panitumumab - bind EGFR

erlotinib, gefitinib - bind to the ATP binding site on the receptor for EGFR

epithelial derived cancers

Question 28

Tyrosine kinase inhibitors - inhibitors of HER2

Answer 28

pertuzumab (first antineoplastic dimerization inhibitor),

trastuzumab (makes HER2 overexpressing cells seem foreign. SE: ventricular dysfunction and CHF.

Ado-trastuzumab emtansine (makes trastuzumab and DM1 (small molecule inhibitor that binds tubulin - like vincristine) in cancer cells)

Question 29

L-asparaginase

what other drug is given with and what is the dosing order

Answer 29

“alterer of intracellular processes”

depletes asparagine

L=asparaginase converts all of the asparagine into aspartate, which the cancer cells (ALL) cannot convert back to asparagine if they have no asparagine synthetase

if methotrexate is given first, you get synergy

If L-asparaginase is given first, MTX is not as effective

Question 30

Bortezomib, carfilzomib

Answer 30

inhibit proteosome

build up of ubiquitin

bort - reversible
car - irreversible

SE: thrombocytopenia, neutropenia, anemia, peripheral neuropathy

Question 31

Romidespin, Vorinostat

Answer 31

inhibit histone deacetylases (HDAC) which are sometimes more active in cancers to silence p53 and other tumor suppressor genes

(deacetylation causes heterochromatin)

IT FREES THE TUMOR SUPPRESSOR GENES

se: pulmonary embolism, deep vein thrombosis

severe thrombocytopenia and GI bleeding result from coadministration with valproic acid
PT and INR are prolonged if given withWARFARIN

Question 32

What type of leukima does differentiation block occur in a lot?

What drugs can you give that help differentiate the cells, leading to their apoptosis?

Answer 32

acute promyelocytic leukemia (APL)

bexarotine - retinoid that activates retinoid X receptors. doesn’t kill cells

Tretinoin (atra) (promotes degredation of PML-RAR fusion protein) - doesn’t kill cells. SE: differentiation syndrome (fever, dyspnea, weight gain, pulminary infiltrates), CNS tox, teratagenic.

Co administered with *arsenic trioxide or *anthracyclin antibiotic to cause cell death. SE: arrhythmias, leukocyte maturation syndrome

Question 33

Bexarotene

Answer 33

Retinoid that activates retinoid X receptors

used for cutaneous T-cell lymphoma

metabolized by CYP3A4

SE: lipid abnormalities, pancreatitis, TERATOGENIC

Question 34

inhibitors of BCR-ABL

Answer 34

bosutinib, dasatinib, imatinib, nilotinib

Question 35

the complicated thing that mTOR does

Answer 35

mTOR regulates translation of p21, which in normally under the control of p53.

mTOR usually stops the cell from progressing through the cell cycle if DNA is damaged.

If we stop mTOR, the cell will keep going and die

Question 36

Immunomodulatory drugs

Answer 36

Lenalidomide
Pomalidomide

Thalidomide - developmental toxin approved for use in Tx of hansen’s disease and MM - SIGNIFICANTLY TERATOGENIC - ALMOST KILLED FITZ AS A FETUS - sedating, restores appetite and decreases wasting “wonder drug to prevent morning sickness” - SE: peripheral neuropathy, DVT, Phocomelia (abbreviated arms and legs in fetuses)

Question 37

MOPP

Answer 37

Mechlorethamine, oncovin = vincristine, prednisone, procarbazine

hodgkin lymphoma

Question 38

COP +/-D

Answer 38

Cyclophosphamide, oncovin = vincristine, prednisone, doxorubicin

non hodgkin lymphoma

Question 39

PVB

Answer 39

testicular cancer

platin (carbo or cis), vinblastine, bleomycin

Question 40

FAC and CMF

Answer 40

breast cancer

5-FU, cyclophosphamide, adriamycin = doxo, methotrexate

Question 41

R-CHOP

Answer 41

rituximab, cyclophosphamide, adriamycin (hydroxydanorubicin - or doxorubicin), vincristine (oncovin), prednisone

Question 42

diffuse large b-cell lymphoma pearls

Answer 42

40% of lymphomas
average age 67

Tx - CHOP

Question 43

what do you do if you suspect lymphoma?

Answer 43

EXCISIONAL BIOPSY OF THE LYMPH NODE