Drugs Used in the Treatment of Leukemias/Lymphomas

Question 1

Doxorubicin (adriamycin) MOA and toxicity

Answer 1

Inhibits Topo 2

Cardio

Question 2

Bleomycin MOA

Answer 2

Causes DNA strand breaks by intercalating…can chelate metals and generate ROS..may target RNA

Question 3

Bleomycin side effects

Answer 3

Allergic runs, skin toxicity, pulmonary firbsosi…due to inflammation and can treat with TNF inhibitor…skin changes due to melanocyte/keratinocyte interaction changes

Question 4

Paclitaxel MOA and toxicity

Answer 4

Arrests MT depolarization

Immunosuppression

Question 5

Vinblastine MOA, metab

Answer 5

Inhibits MT formation
Neuropathy
P450 metab

Question 6

Dacarbazine side effects and metab

Answer 6

Toxic to bone marrow
Modified in by CYP1A1, CYP1A2, and CYP2E1 into active diazomethane form…these have low levels so limit activity in vivo

Question 7

Targets of ABVD

Answer 7

A - topo 2 in G2
B - G2
V - S prevent MT
D - G1 damage directly

Question 8

Bretuximab use and MOA

Answer 8

Second line refractory Hodgkin 
Targets CD30 (which is TNFR and receptor for CD153)
Conjugate of antibody to a mitotic inhibitor called auristatin via a peptide bond...goes into cell and releases auristatin

Question 9

NHL regiment

Answer 9

Cyclophosphamide, doxorubicin, vincristine, prednisone…may also add retixumab and ondansetron

Question 10

Rituximab

Answer 10

Another option for patient with TNF inhibitor restart RA…used with methotrexate

Binds to CD20(cell surface Ca channel needed on B cells) and triggers cell death

Used for Bcell lymphomas

Chimeric

Question 11

Rituximab side effect, preconditions

Answer 11

Immunosuppression

Worried about prior infections

Question 12

Antibody clearance

Answer 12

By RES, lived for 3-12 days

Can be affected by immune system status

Question 13

CLL tx

Answer 13

Nucleoside analog with Cyclophosphamide, vincristine, prednisone, or doxo

Almost identical to NHL

Question 14

Cytarabine MOA

Answer 14

Converted to mono, di, and triphosphate forms…latter is competitive inhibitor of DNA polymerase alpha (primate) and beta (base excision repair)

Also incorporated into RNA and DNA blocking chain elongation

Question 15

Cytarabine PK/PD ad main use

Answer 15

Cleared rapidly and must be continually infused

Only used for hematological cancers because of qukc clearance

Side effects typical for chemo

Question 16

Asparaginase

Answer 16

Used for ALL
Can cause tumor lysis syndrome
Deprive leukemic cells of asparagine that they cannot synthesize

Question 17

ALL tx

Answer 17

Methotrexate, cytarabine, vincristine, dexamethasone

Question 18

Blimatumomab

Answer 18

Used for ALL

Binding sites for CD3 (T) and CD19 (B)…activates T cell to kill B cell

Question 19

AML tx

Answer 19

Cytarabine plus anthracycline

Often get filgastrim as well

Question 20

G-CSF

Answer 20

Filgastrim

Enhance neutrophil recovery after chemotherapy

Question 21

CML tx

Answer 21

Imatinib

Question 22

MM tx

Answer 22

Bortezomib, lenalidomide, dexamethasone

Question 23

Bortezomib MOA

Answer 23

Inhibits IkB degradation…IkB inhibits NFkB that is often mutated in MM

Boron on one end and binds to 26s subunit of proteasome
Cleared quick
Neuropathy and myelosuppression…shingles

Question 24

Lenalidomide

Answer 24

Used for MM…don’t know mechanism

Question 25

Cyclophosphamide MOA

Answer 25

Alkylating agent targets DNA

Question 26

Prednisone MOA

Answer 26

Binds glucocorticoid receptors

Question 27

Crizotinib

Answer 27

Inhibits ALK