where do most brain mets go?
cerebral hemispheres
What is the main concern for treating brain tumors?
BBB is hard to cross for traditional chemo. Astrocytes may be involved in tumor cell survival (cross talk and gene upregulation, decrease tumor cell apoptosis
- gap junctions help mediate communication btw tumor cells and astrocytes
What are resistance mechanisms for tumors to evade chemo?
decrease drug uptake, decrease drug metabolic activation, increase drug metabolism, increase drug efflux, repair of drug induced DNA damage, gene alteration, binding site alteration, increase sulfhydryl scavengers, increase Bcl-2
MOA temozolomide
prodrug DNA methylating agent. Cat X
ADE Temozolomide
myelosuppression, leukopenia, thrombocytopenia, N/V, chills, fever, malaise, myalgia
How can tumor cells get resistance to temozolomide?
- express WT MGMG - a DNA repair protein that excises toxic methyl lesions from O6 position of guanine residues
- – hematopoietic stem cells have very low levels of MGMT and thus killed by TMZ
MOA of nitrosoureas - mustines!
DNA alkylators; decreased cross resistance w/ others
- Carmustine - also carbamoylates (inhibits DNA repair)
ADE of mustines?
- regular chemo ADE
- Pulmonary fibrosis
- Endocrine dysfunction w/ brain irridation
- Encephalopathy and seizures –> dementia
- increases transmainases, ALP, and high bilirubin
What is the convection enhanced delivery?
- installation of catheter and infusion under pressure
- catheter can be placed directly into the tumor and drug can bypass the BBB
What is the chemo fog?
long term AE of chemo
- damage to hippocampus, amygdala, cerebellum
- impaired memory, learning, language, attention, etc
- may be from increased TNF alpha - it can cross BBB and may damage mitochondria
- TNFalpha mabs may be used in future
