chemotherapy

Question 1

which cells represent majority of cells in tumor

Answer 1

stromal cells

Question 2

malignant vs benign tumors

Answer 2

malignant- non differentiated, grow faster, not encapsulated, metastasis and invasion
benign- differentiated, grow slow, encapsulated, NO metastasis or invasion

Question 3

cell cycle specific vs non specific cytotoxic drugs

Answer 3

cell cycle specific: paclitaxel, vincristine. treat high growth fractions, toxicity depends on duration of exposure
nonspecific: nitrosourea, cyclophosphamide. treat high and low growth fractions, toxicity dose dependent

Question 4

Chemo drug resistance mechanisms

Answer 4

upregulation of inactivating enzymes, downregulation of activating enzymes, more abundant target molecules, mutation in target, more DNA repair enzymes, ABCB1 (transporter responsible for efflux of chemo drugs)

Question 5

adjuvant, neoadjuvant, and radiosensitization

Answer 5

adjuvant- surgery then chemo to get any residual
neoadjuvant- chemo before surgery so less to take out
radiosensitization- chemo to make radiation more effective

Question 6

Direct DNA Damaging cytotoxic drugs

Answer 6

hot dog mnemonic
nitrogen mustards (alkylating crosslinkers): mechlorethamine and cyclophosphamide
platinum drugs (non alkylating cross linkers): cisplatin, oxaliplatin

Question 7

Direct DNA damaging cytotoxic drugs TOXICITIES

Answer 7

nitrogen mustards/alkylating drugs:
mechlorethamine and cyclophosphamide DLT myelosuppression
***cyclophosphamide- doesnt directly interact w DNA. needs p450, makes acrolein which causes HEMORRHAGIC CYSTITIS. MESNA helps this.

platinum/nonalkylating drugs:

cisplatin: renal DLT cumulative
oxaliplatin: neurotoxicity DLT cumulative

Question 8

special points about Direct DNA Damaging cytotoxic drugs (cyclophosphamide, mechlorthamine, cisplatin, and oxaliplatin)

Answer 8

vesicants (except cyclophosphamide)
renal excretion (except cyclophosphamide)
cyclophosphamide hemorrhagic cystitis can be prevented with hydration and MESNA
platinum drugs (cisplatin and oxaliplatin) interact with aminoglycosides, furosemide and vinca alkaloids)

Question 9

Other Direct DNA Damaging agents (besides nitrogen mustards and platinum drugs)

Answer 9

ifosfamide (bladder toxicity)
temozolomide (crosses BBB)
Bleomycin (lung toxicity, for Hodgkins Lymphoma)
Dacarbazine (Hodgkins Lymphome)

Question 10

Antimetabolite cyctotoxic drugs

Answer 10

5-FU (pyrimidine analog)-Leukovorin increases potency, Methotrexate (folate analog)-Leukovorin decreases toxicity, 6-mercaptopurine (Purine analog)

Question 11

MTX resistance

Answer 11

decreased folate transporters, increased DHFR expression, less polyglutamylation (glu-glu-glu allows MT to “stick” around longer in the cell)

Question 12

Antimetabolite toxicities (MTX and fluorouracil)

Answer 12

Fluorouracil (5-FU)- myelo suppression DLT with bolus injection. GI DLT with cont IV infusion
MTX- myelo suppression and GI DLT

Question 13

Other antimetabolites besides 5FU and MTX

Answer 13

cytarabine, mercaptopurine, fludarabine (leukemias)
gemcitabine (radiosensitizer)
capecitabine (oral fluorouracil)
pemetrexed (inhibits thymidylate synthesis)

Question 14

Chromosomal structure antagonists

Answer 14

pacman microtubules drinking wine, dan rubinger topoisomerase
Microtubule antagonists- paclitaxel and vincristine
Topoisomerase antagonists- doxorubicin and irinotecan

Question 15

Chromosomal antagonists toxicities

Answer 15

vincristine- neurotoxicity
paclitaxel- myelosuppression
doxorubicin- myelosuppression and cardiotoxic
irinotecan- myelosuppression and GI

Question 16

chromosomal antagonists special points

Answer 16

irinotecan needs an activator, and the enzyme required for elimination causes toxicity
most are vesicants

Question 17

other chromosomal antagonsits

Answer 17

“vins”
“tax”
“rubicin”
“tecans”

Question 18

target therapy: nibs vs mabs

Answer 18

nibs: small molecules, tyrosine kinase
mabs: target is receptor ectodomain, most specific