Combo Delivery

Question 1

5 curative cancers

Answer 1

1. Acute lymphocytic Leukemia (peds especially)
2. some pediatric sarcomas
3. germ cell tumors
4. aggressive and intermediate lymphomas
5. acute myeloid leukemia (in young)

Question 2

Mechanisms of chemo resistance?

Answer 2

Altered apoptosis threshold
Drug avoidance mechanisms
Toxicity to host

Question 3

Drug avoidance mechanisms

Answer 3

1. down regulating transport mechanism
2. upregulating drug efflux
3. down regulating metabolic pathways

Question 4

Venetoclax action

Answer 4

Targets Bcl-2 to restore pro-apoptotic signals

Question 5

Venetoclax

Answer 5

mimics BH3 domain which is a natural inhibitor of the anti-apoptotic Bcl-2

Question 6

How does BH3 promote apoptosis

Answer 6

promotes cytochrome C release from mitochondria

Question 7

why is Venetoclax so special?

Answer 7

rare to find small molecules that mimic protein-protein interactions

Question 8

Venetoclax DLT?

Answer 8

so potent that is causes excessive tumor lysis syndrome if not given carefully.

Question 9

Antagonistic

Answer 9

1 + 1

Question 10

Ineffective

Answer 10

1 + 1 = 1

Question 11

Additive

Answer 11

1 + 1 = 2

Question 12

Synergistic

Answer 12

1 + 1 > 2

Question 13

Curative

Answer 13

some fractions of patients will be cured.

curative intent - cures at least 5% of people

Question 14

Control

Answer 14

Less than 5% chance of cure, provides reasonable chance of altering natural history of disease so patients will live longer

Question 15

Palliative

Answer 15

Alleviates symptoms or pre emptively addresses an issue that will reliably be morbid,

Question 16

Textbook principles of combination chemo

Answer 16

• use agents with different MOA

- Use agents with non-overlapping toxicity

Question 17

catch phrase for using agents of different mechanistic classes?

Answer 17

non-cross resistant

Question 18

Bleomycin

Answer 18

natural, made by streptomyces. induces DNA strand breaks.

Question 19

Bleomycin

Answer 19

little myelosuppression, doesn’t drive down WBC

Question 20

Bleomycin use

Answer 20

lymphoma

Question 21

Bleomycin warning

Answer 21

causes fatal pulmonary fibrosis. Risk higher in smokers and is prohibited in the presence of pulmonary hemorrhage or pulmonary embolism.

Question 22

BEP stands for…

Answer 22

Bleomycin, Etoposide, Cisplatin

Question 23

BEP uses

Answer 23

Germ cell tumors

Question 24

RCHOP stands for…

Answer 24

Rituximab, Cytoxan, Doxorubicin, Vincristine, Prednisone

Question 25

RCHOP uses

Answer 25

intermediate risk non-Hodgkin lymphoma (curative 80% of time)

Question 26

ABVD stands for…

Answer 26

Doxorubicin, Bleomycin, Vinblastine, Dacarbazine

Question 27

ABVD use

Answer 27

Hodgkins (90% cure)

Question 28

3 + 7

Answer 28

Daunorubicin, Ara-C

Question 29

3 + 7 use

Answer 29

AML

Question 30

AC - T

Answer 30

Doxorubicin, Cyclophosphamide, Taxane

Question 31

AC-T use

Answer 31

breast cancer

Question 32

4 delivery systems

Answer 32

Liposomes
Targeted Liposomes
Antibody drug conjugates
Drugs with polymers

Question 33

Liposomal Doxorubicin

Answer 33

Safer cardiac

More hand/foot syndrome

Question 34

Brentuximab Vedotin

Answer 34

Very active drug against CD-30 expressing lymphomas (most all Hodgkin lymphomas)
Built from an antibody and a highly toxic anti-tubule drug that is way too toxic to be used in non-targeted way

Question 35

Trastuzumab - Maytansine (T-DM1)

Answer 35

Important for Her2 expressing breast cancers

Highly toxic antitubule that is too toxic to be used in non targeted way