Cell Cycle Specific Agents

Question 1

Gompertzian model

Answer 1

Human solid tumor
PT with advanced cancer is tx, tumor mass is larger, growth fraction low, fraction of killed cells low
Response to chemo depends on where tumor is in growth curve

Question 2

Cytotoxicity

Answer 2

Normal tissue that proliferates rapidly highly susceptible to damage from cytotoxic drugs

Question 3

Cell cycle specificity

Answer 3

The greater the fraction of cells in replicating cycle, the more susceptible to chemotherapy
Non cycle specific: activity against slowly growing cancers

Question 4

Chemotherapy regimen goals

Answer 4

Therapeutic yet non toxic outcome
As close and as frequent to max tolerance to discourage re growth
Avoid overlapping major toxicities
Efficacy: only drugs known to be somewhat effective alone should be given in combo
Toxicity: least toxic in class as possible
Mechanisms of interaction for each drug
Avoid arbitrary dose changes

Question 5

ADE common to most cytotoxic

Answer 5

Quickly replicating cells
Bone marrow: myelosuppression
Anemia, neutropenia, thrombocytopenia
Epithelial cells
Reproductive tissue
Activation of chemoreceptor trigger zone = n/v
CiSPLATin is highly emetigenic
Necrosis from extravasation of vesicants
Secondary malignancy

Question 6

Methotrexate

Answer 6

Interferes with formation of DNA, RNA, and key cellular proteins
Nonproliferating cells are resistant
Leucovorin (folinic acid) bypasses blocked enzyme and replenishes folate pool

Question 7

5-fluorouracil

Answer 7

Results in inhibition of DNA syn through “thymineless death”
Cytotoxicity -> combined effects on DNA and RNA mediated events
Enhanced by leucovorin

Question 8

Cytarabine

Answer 8

S phase specific
Active metabolite compatibly inhibits DNA polymerase resulting in blockade of DNA synthesis and repair
Toxicities: myelosuppression, panocytopenia

Question 9

6-Metacaptopruine (6-MP)

Answer 9

Inhibits enzymes of de novo purine syn
Inactivated by oxidation rxn catalyzed by XO
Allopurinol used as supportive care in tax of acute leukemia to prevent dev of hyperuricemia that occurs with tumor cell lysis

Question 10

Vinblastine

Answer 10

Vinca alkaloid
Inhibits tubular polymerization which disrupts assembly of microtubules resulting in mitotic arrest in M phase, halting cell division, leading to cell death

Question 11

Vincristine

Answer 11

Vinca alkaloid
Dose limiting neurotoxicity usually exp as peripheral sensory neuropathy through ANS dysfunction with orthostatic hypotension, urinary retention, constipation, ataxia, seizures, and coma

Question 12

Paclitaxel

Answer 12

Promotes microtubule assembly in absence of associated proteins and inhibits mitosis and cell division (spindle cannot break down)
Peripheral neuropathy

Question 13

Etoposide

Answer 13

Binds to topisomerase II and prevents resealing of break

Question 14

Irinotecan

Answer 14

Inhibits topisomerase I inhibits re-litigation and accumulation of single stranded breaks in DNA
Ongoing DNA syn necessary for cytotoxicity
Dose limiting toxicity is diarrhea w/ or w/o neutropenia

Question 15

Bleomycin

Answer 15

Inhibits DNA syn by single and double stranded breaks
Pulmonary toxicity is dose limiting
Pneumonitis with cough, dyspnea, dry inspirations crackles and infiltrates on X-ray

Question 16

Hydroxyurea

Answer 16

S phase specific
Inhibits ribonucleoside reductase
Radiation sensitizing activity by maintaining cells in G1-S boundary and interfering with DNA repair