28 Pharmacology and Toxicity of Antineoplastic Drugs

Question 1

For bilirubin >1.5 mg/dL reduce initial dose by

Answer 1

50%

Question 2

For bilirubin >3.0 mg/dL reduce initial dose by

Answer 2

75%

Question 3

TRUE OR FALSE

Individual agents in a combination should have different mechanisms of action and should have nonoverlapping and should not have overlapping mechanisms of resistance.

Answer 3

TRUE

Individual agents in a combination should have different mechanisms of action and should have nonoverlapping and should not have overlapping mechanisms of resistance.

Question 4

While most chemotherapy agents have toxicity for marrow and epithelium, certain drugs, such as____________ are particularly valuable because their toxicities do not overlap with cytotoxics, which allows them to be used in combination at full doses.

Answer 4

Bleomycin, prednisone, and antibodies

Question 5

____________ and __________ are potent radiosensitizers and are often used with radiation therapy to improve local tumor control of the head and neck and gastrointestinal cancers.

Answer 5

5-fluorouracil and cisplatin

Question 6

The toxicity of radiation therapy to normal tissues such as skin, lung, heart, and brain is markedly enhanced by concurrent administration of _____________________

Answer 6

Anthracyclines, bleomycin, or gemcitabine

Question 7

Antimetabolites are analogues of normal metabolites kill cells most effectively during the DNA _____________________.

Answer 7

Synthetic phase (S-phase) of the cell cycle

For these agents, a prolonged period of tumor exposure to drug is essential so as to maximize the number of cells exposed during the vulnerable period of the cell cycle.

Question 8

_______________________ do not require cells to be exposed during a specific phase of the cell cycle, although like the antimetabolites, these drugs are generally more effective against actively proliferating cells as compared to resting cells.

Answer 8

Topoisomerase inhibitors and alkylating agents

Question 9

_________________ and ____________, are equally toxic to dividing and nondividing cells, and at the same time, deplete marrow stem cells.

Answer 9

Nitrosoureas and busulfan

Question 10

TRUE OR FALSE

In general, the toxicity of alkylating agents is determined by the total dose of drug, whereas the toxicity of the cell-cycle-specific drugs (such as MTX and cytarabine) depends upon both drug concentration and duration of exposure.

Answer 10

TRUE

In general, the toxicity of alkylating agents is determined by the total dose of drug, whereas the toxicity of the cell-cycle-specific drugs (such as MTX and cytarabine) depends upon both drug concentration and duration of exposure.

Question 11

For taxanes, which block mitosis, myelosuppression correlates best with the duration of exposure above a threshold plasma concentration, which is approximately _________nM for paclitaxel and_______ nM for docetaxel.

Answer 11

50–100 nM : Paclitaxel

200 nM: Docetaxel

Question 12

Cells are thus most vulnerable during periods of active DNA synthesis __________, and least affected during quiescent (_______) stages of their life cycle.

Answer 12

S-phase

G0

Question 13

Enters cells by active uptake process mediated by the reduced folate transporter and is actively effluxed from cells by the MRP class of exporters.

Answer 13

MTX

Question 14

TRUE OR FALSE

MTX is well absorbed orally at low doses (5–10 mg/m2), but at doses above 30 mg/m2 absorption is variable, requiring the MTX to be orally administered.

Answer 14

FALSE

MTX is well absorbed orally at low doses (5–10 mg/m2), but at doses above 30 mg/m2 absorption is variable, requiring the MTX to be parenterally administered.

Question 15

MTX is primarily cleared by excretion of unchanged drug through the _______________.

Answer 15

kidney

Question 16

Patients receiving HD-MTX can be rescued from drug toxicity by administering small doses of ________________, which replenishes the intracellular pool of reduced folates in a competitive manner with MTX.

Answer 16

N-10-formyltetrahydrofolate (leucovorin)

Question 17

Dose of leucovorin

Answer 17

10–25 mg/m2 at 6-hour intervals, starting 6–24 hours after the infusion of MTX

Question 18

Leucovorin continues until plasma levels of MTX fall below ______ μM.

Answer 18

1 μM

Question 19

The primary cause of decreased drug clearance and overwhelming toxicity during HD-MTX treatment.

Answer 19

Drug-induced renal dysfunction

Question 20

Serious toxicity from MTX can be prevented by vigorous pretreatment hydration of _______L/24 h during drug infusion and by raising the urine pH higher than _______ with intravenous sodium bicarbonate prior to and during therapy.

Answer 20

2.5 L/24 h

higher than 7

Question 21

A commercially available bacterial enzyme that instantly degrades extracellular antifolates and prevents further toxicity

Answer 21

Glucarpidase