Treatment of brain tumors

Question 1

effect of astrocytes on cancer cells

Answer 1

tumor cells harness and adopt neuro-protective properties of astrocytes for their own survival; gap-junction mediated communication between astrocytes and tumor cells lead to the upregulation of genes that promote tumor cell survival; the protein products of these genes protect tumor cells by interrupt apoptosis and provide “survival signaling” in the presence of chemotherapeutic agents

Question 2

temozolomide moa

Answer 2

non-enzymatically activated pro-drug that is a DNA methylating agent

Question 3

temozolomide adverse effects

Answer 3

myelosuppression, leukopenia, and thrombocytopenia; n/v common; chills, fever, malaise, and myalgias; teratogenic

Question 4

tumors you can use temozolomide on

Answer 4

labeled: astrocytoma, GBM

off-labeled, recommended: malignant glioma, malignant melanoma

Question 5

TMZ resistance

Answer 5

upregulation of MGMT, excises methyl groups added by the TMZ from the O6 position of guanine residues

Question 6

carmustine (BCNU) moa

Answer 6

alkylating agent; decomposition products carbamolyate proteins and inhibit DNA repair

Question 7

lomustine (CCNU)

Answer 7

alkylating agent

Question 8

nitrosourea pharmacology

Answer 8

highly lipophilic and non-ionized; high conc. enter the CNS; hepatic metabolism

Question 9

lomustine route of administration

Answer 9

oral

Question 10

carmustine route of administration

Answer 10

parenteral

wafer insertion after surgical removal

Question 11

nitrosourea adverse effects

Answer 11

thrombocytopenia, leucopenia, N/V
delayed pulmonary fibrosis and/or infiltrates
endocrine dysfunction with brain irradiation - hyperprolactinemia and hypothyroidism (low T4)
encephalopathy and seizures; deterioration to dementia
increased transaminase, alk. phos. and bilirubin levels