Tx of Brain Tumors

Question 1

MCC of brain tumors?

Answer 1

Brain metastases

Question 2

Most common primary cancers resulting in metastases to the brain.

Answer 2

Lung, breast, melanoma, colon

Question 3

Where do most brain metastases occur?

Answer 3

Cerebral hemispheres

Question 4

Other drugs that may be used in treatment of metastases?

Answer 4

Steroids (edema) and anticonvulsants (Seizures)

Question 5

T/F: There is a lack of strong evidence to support the routine use of conventional chemo in the mgmt of patients with brain metastases.

Answer 5

True

Question 6

Two common resistance mechanisms seen in brain tumors.

Answer 6

Crossing BBB and overexpression of P-gp by tumor cells

Question 7

What cell type can aid tumor cells in increasing resistance to chemo?

Answer 7

Astrocytes

Question 8

How do tumor cells and astrocytes communicate?

Answer 8

Gap junctions

Question 9

What are the possible mechanisms utilized by astrocytes that helps them to cause an increased resistance to chemo?

Answer 9

Interrupting apoptotic signaling and providing survival signalling

Question 10

MOA of temozolomide

Answer 10

DNA methylating agent (pro drug)

Question 11

ADE of temozolomide

Answer 11

Myelosuppression, leukopenia, thrombocytopenia

Question 12

Is temozolomide a teratogen

Answer 12

Yes

Question 13

What cancers would temozolomide be used in?

Answer 13

Astrocytoma, glioblastoma multiforme, malig glioma, and malig melanoma

Question 14

What enzyme can be upregulated by tumor cells to help increase resistance to temozolomide?

Answer 14

MGMT

Question 15

If a patient’s tumor cells have increased MGMT, will ADEs associated with temozolomide still be seen?

Answer 15

Yes (hematopoietic cells lack the capability to upregulate MGMT)

Question 16

BCNU/carmustine used in what cancers?

Answer 16

Astrocytoma, brain met, malig glioma, medulloblastoma

Question 17

CCNU/lomustine used in what cancers?

Answer 17

Malig glioma

Question 18

MOA of BCNU and CCNU

Answer 18

Alkylators

Question 19

Special MOA of BCNU/carmustine.

Answer 19

Carbamoylate proteins (inhibits DNA repair!!!)

Question 20

T/F: Cross resistance with other alkylating agents is uncommon.

Answer 20

True

Question 21

How is lomustine given? carmustine?

Answer 21

Orally; parentally

Question 22

ADE of carmustine and lomustine.

Answer 22

Pulmonary fibrosis and endocrine dysfunction (hyperprolactinemia and hypothyroidism)

Question 23

Name two novel ways to use BCNU that help to minimize the affect the drug can have on other locations in the brain.

Answer 23

Local application technique (wafer) and convection enhanced delivery (catheter)

Question 24

What is chemo-fog?

Answer 24

chemo related cognitive impairment

Question 25

What areas can be impaired due to long-term consequence of chemo therapy?

Answer 25

Vebal and visual memory, attn, concentration, language, motor skills, etc

Question 26

What cytokine may be responsible for chemo-fog?

Answer 26

TNF-alpha

Question 27

How does TNF-alpha produce the effects seen in chemo-fog?

Answer 27

Damages mitochondria and produces ROS (Tnf-alpha can cross the BBB)