treatment of brain tumors

Question 1

what two other classes may be used in the treatment of brain mets?

Answer 1

steroids (to treat brain edema)

anticonvulsants ( to treat seizures)

Question 2

what are some of the resistance mechanisms to antineoplastic agents?

Answer 2

decreased uptake of drug into cancer cell
failure to be metabolized into pharm. active drug
enhanced metab. to inactive product
incrased active transport of drug out of cancer cell

Question 3

what are some of the resistance mechanisms to DNA, Target enzyme or other macromolecule?

Answer 3

repair of drug-induced DNA damage
Gene amplification
reduced ability of drug to bind target enzume
increased levels of sulhydryl scavengers
altered concentrations of target proteins
increased expression of antiapoptotic genes like bcl-2

Question 4

how do astrocytes & tumor cells work together to have increased resistance to chemotherapy?

Answer 4

they have gap junctions between astrocytes and tumors cells (interrupt the apoptotic process and provide prevailing survival signaling)
-even if chemo agent could reach brain tissue, the drug probably won’t work

Question 5

MOA temozolomide

Answer 5

non-enzymatically activated pro-drug yielding a DNA methylating agent

Question 6

what are the key AEs for temozolomide?

Answer 6

myelosuppression; leukopenia & thrombocytopenia, usually midl-moderate (teratogen)

Question 7

temozolomide is labeled to treat what two types of brain tumors?

Answer 7

astrocytoma, glioblastoma multiforme

Question 8

why does temozolomide produce dose-dependent myelosuppressive effects?**

Answer 8

methylation damage to DNA that is repaired by tumor cells that make MGMT which can demethylate and fix DNA, normal stem cells lack MGMT and so stem cells die

Question 9

how does MGMT work?

Answer 9

DNA repair protein that excises toxic methyl lesions from the O6 position of guanine residues

Question 10

Carmustine (BCNU) is used to treat which brain tumors?

Answer 10

astrocytomas
brain mets
malignant glioma
medulloblastoma

Question 11

Lomustine is used to treat what brain tumors?

Answer 11

malignant glioma

Question 12

MOA Carmustine

Answer 12

alkylator that inhibits DNA repair, carmustine decomposition products carbamolyate proteins (has two mechanisms)

Question 13

MOA lomustine

Answer 13

alkylator

Question 14

how is lomustine administered?

Answer 14

oral

Question 15

how is carmustine administered?

Answer 15

parenteral

Question 16

describe the PK of carmustine & lomustine

Answer 16

highly lipophilic & non-ionized at physiologic pH

-enter the CNS in measurable concentrations

Question 17

what are some of the unique adverse effects of carmustine & lomustine?

Answer 17

delayed pulmonary fibrosis
endocrine dysfunction w/ brain irradiation (hyperprolactinemia & hypothyroidism)
Encephalopathy & seizures; deterioration –> dementia
Raised transaminases, AlkPhos, & hyperbilirubinemia

Question 18

which chemo drug used on brain cancers comes available in a wafer form that is put in the tumor site after surgical excision of the tumor?

Answer 18

carmustine

Question 19

what is the long term consequence of anti-braintumor treatment with cytotoxic agents?

Answer 19

chemo-fog

Question 20

describe chemofog

Answer 20

impaired verbal & visual memory, attention, concentration, language, motor skills, multitasking and ability to organize info

Question 21

cytotoxic antitumor drugs promote peripheral release of what inflammatory cytokine in response to cellular damage?

Answer 21

TNF-alpha (can cross the BBB)

Question 22

what happens after TNF-alpha gets inside the brain?

Answer 22

damages mitochondria and produces reactive nitrogen species via glial cell-related mechanism

Question 23

what is survivor care?

Answer 23

refers to the long term needs of pts who suffer impaired cognitive function from chemo therapy

Question 24

what is the term for drug delivery technique that involves the installation of a catheter and the infusion under pressure of a chemotherapeutic agent which will diffuse into the tumor and immediately surround tissue?

Answer 24

convection enhanced delivery