treatment of brain tumors Flashcards
what two other classes may be used in the treatment of brain mets?
steroids (to treat brain edema)
anticonvulsants ( to treat seizures)
what are some of the resistance mechanisms to antineoplastic agents?
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
what are some of the resistance mechanisms to DNA, Target enzyme or other macromolecule?
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
how do astrocytes & tumor cells work together to have increased resistance to chemotherapy?
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
MOA temozolomide
non-enzymatically activated pro-drug yielding a DNA methylating agent
what are the key AEs for temozolomide?
myelosuppression; leukopenia & thrombocytopenia, usually midl-moderate (teratogen)
temozolomide is labeled to treat what two types of brain tumors?
astrocytoma, glioblastoma multiforme
why does temozolomide produce dose-dependent myelosuppressive effects?**
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
how does MGMT work?
DNA repair protein that excises toxic methyl lesions from the O6 position of guanine residues
Carmustine (BCNU) is used to treat which brain tumors?
astrocytomas
brain mets
malignant glioma
medulloblastoma
Lomustine is used to treat what brain tumors?
malignant glioma
MOA Carmustine
alkylator that inhibits DNA repair, carmustine decomposition products carbamolyate proteins (has two mechanisms)
MOA lomustine
alkylator
how is lomustine administered?
oral
how is carmustine administered?
parenteral
describe the PK of carmustine & lomustine
highly lipophilic & non-ionized at physiologic pH
-enter the CNS in measurable concentrations
what are some of the unique adverse effects of carmustine & lomustine?
delayed pulmonary fibrosis
endocrine dysfunction w/ brain irradiation (hyperprolactinemia & hypothyroidism)
Encephalopathy & seizures; deterioration –> dementia
Raised transaminases, AlkPhos, & hyperbilirubinemia
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?
carmustine
what is the long term consequence of anti-braintumor treatment with cytotoxic agents?
chemo-fog
describe chemofog
impaired verbal & visual memory, attention, concentration, language, motor skills, multitasking and ability to organize info
cytotoxic antitumor drugs promote peripheral release of what inflammatory cytokine in response to cellular damage?
TNF-alpha (can cross the BBB)
what happens after TNF-alpha gets inside the brain?
damages mitochondria and produces reactive nitrogen species via glial cell-related mechanism
what is survivor care?
refers to the long term needs of pts who suffer impaired cognitive function from chemo therapy
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?
convection enhanced delivery
