Topoisomerase Inhibitors

Question 1

What drugs are in the Topoisomerase Inhibitors class?

Answer 1

Drugs in this class are:
- lrinotecan
- Topotecan
- Etoposide
- Teniposide
- Mitoxantrone

Question 2

What is the brand name of lrinotecan?

Answer 2

The brand name of this generic drug is:
- Camptosar

Question 3

What is the brand name of Topotecan?

Answer 3

The brand name of this generic drug is:
- Hycamtin

Question 4

What is the brand name of Etoposide?

Answer 4

The brand name of this generic drug is:
- Toposar, Vepesid, VP16

Question 5

What is the brand name of Teniposide?

Answer 5

The brand name of this generic drug is:
- VM26

Question 6

What is the brand name of Mitoxantrone?

Answer 6

The brand name of this generic drug is:
- Novantrone

Question 7

What is the generic of name of Camptosar?

Answer 7

The generic name of this brand name drug is:
- lrinotecan

Question 8

What is the generic of name of Hycamtin?

Answer 8

The generic name of this brand name drug is:
- Topotecan

Question 9

What is the generic of name of Toposar?

Answer 9

The generic name of this brand name drug is:
- Etoposide

Question 10

What is the generic of name of Vepesid?

Answer 10

The generic name of this brand name drug is:
- Etoposide

Question 11

What is the generic of name of VP16?

Answer 11

The generic name of this brand name drug is:
- Etoposide

Question 12

What is the generic of name of VM26?

Answer 12

The generic name of this brand name drug is:
- Teniposide

Question 13

What is the generic of name of Novantrone?

Answer 13

The generic name of this brand name drug is:
- Mitoxantrone

Question 14

What are the main indications for use of lrinotecan?

Answer 14

The main indications of this drug are:
- Non-Small Cell Lung Cancer
- Small Cell Lung Cancer
- Colorectal Cancer
- Esophageal Cancer
- Gastric Cancer
- Pancreatic Cancer

Question 15

What are the main indications for use of Topotecan?

Answer 15

The main indications of this drug are:
- Small Cell Lung Cancer
- Cervical Cancer
- CNS Malignancy
- Ewing Sarcoma
- Ovarian Cancer
- Rhabdomyosarcoma

Question 16

What are the main indications for use of Etoposide?

Answer 16

The main indications of this drug are:
- Breast Cancer
- Hematopoietic Stem Cell Transplant
- Hemophagocytic Lymphohistiocytosis
- Hodgkin Lymphoma
- Non-Hodgkin Lymphoma
- Non-Small Cell Lung Cancer
- Small Cell Lung Cancer
- Testicular Cancer

Question 17

What is the class and MOA of lrinotecan?

Answer 17

This drug in the following class:
- Topoisomerase I Inhibitors

This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase I introduces single stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.

Question 18

What is the class and MOA of Topotecan?

Answer 18

This drug in the following class:
- Topoisomerase I Inhibitors

This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase I introduces single stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.

Question 19

What is the class and MOA of Etoposide?

Answer 19

This drug in the following class:
- Topoisomerase II Inhibitors (Podophyllotoxin Derivative)

This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase II introduces double stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.

Question 20

What is the class and MOA of Teniposide?

Answer 20

This drug in the following class:
- Topoisomerase II Inhibitors (Podophyllotoxin Derivative)

This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase II introduces double stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.

Question 21

What is the class and MOA of Mitoxantrone?

Answer 21

This drug in the following class:
- Topoisomerase II Inhibitors (Anthracenedione)

This drug’s MOA is as follows:
- Topoisomerase is an essential enzyme found in all nucleated cells and is responsible for the regulation of DNA topology.
- DNA is wound around basic proteins called histones and supercoiled however, DNA must be relaxed before it can be copied. Topoisomerase II introduces double stranded nicks into DNA to allow DNA relaxation.
- In the presence of topoisomerase inhibitors, these nicks remain and the DNA is damaged causing cell death.

Question 22

What is the emetic potential of Etoposide?

Answer 22

The emetic potential of this drug is:
- Low

Question 23

What is the emetic potential of Topotecan?

Answer 23

The emetic potential of this drug is:
- Low

Question 24

What is the emetic potential of Irinotecan?

Answer 24

The emetic potential of this drug is:
- Moderate

Question 25

What is the emetic potential of Teniposide?

Answer 25

The emetic potential of this drug is:
- Low

Question 26

What is the emetic potential of Mitoxantrone?

Answer 26

The emetic potential of this drug is:
- Low

Question 27

Describe the emetic potential of the Topoisomerase Inhibitors class.

Answer 27

The emetic potential of this drug class is:
- All low except for topotecan (moderate)

Question 28

Describe the extravasation risk and management strategies for the Topoisomerase Inhibitors class.

Answer 28

The extravasation risk and management strategies for this drug class are as follows:
- All irritants except for mitoxantrone (irritant with vesicant like properties)

Question 29

Describe the metabolism of lrinotecan.

Answer 29

The metabolism of this drug is as follows:
- In patients with hepatic dysfunction, clearance is decreased and exposure to the active metabolite (SN-38) is increased proportional to the degree of hepatic impairment.

Question 30

Describe the metabolism of Etoposide.

Answer 30

The metabolism of this drug is as follows:
- In renal function impairment, total body clearance is reduced, AUC is increased, and Vd is lower.

Question 31

Describe the metabolism of Topotecan.

Answer 31

The metabolism of this drug is as follows:
- AUC after oral administration is 30% higher in Asian patients as compared to white patients.

Question 32

What are the notable ADRs of lrinotecan?

Answer 32

The notable ADRs of this drug are:
- Diarrhea
- Neutropenia if homozygous for the UGT1A1*28 allele

Question 33

What drug(s) of the Topoisomerase Inhibitors class is notable for causing Diarrhea?

Answer 33

The drugs in this class notable for cause this condition are:
- Irinotecan

Question 34

Describe the strategy and rationale for management of EARLY onset diarrhea caused by Irinotecan.

Answer 34

The strategy and rationale for management of this condition caused by this drug are:
- Early-onset diarrhea occurs during or within 24 hours of infusion.
- This is caused by direct inhibition of acetylcholinesterase by the drug and is accompanied with cholinergic symptoms such as cramps, diaphoresis, flushing, salivation, visual disturbances, and lacrimation.
- Acute diarrhea is treated with atropine 0.25-1 mg SO or IV. Patients may also be given atropine as secondary prophylaxis after experiencing acute diarrhea in previous chemotherapy cycles.

Question 35

Describe the strategy and rationale for management of LATE onset diarrhea caused by Irinotecan.

Answer 35

The strategy and rationale for management of this condition caused by this drug are:
- Late-onset diarrhea is the dose limiting toxicity of this drug and typically occurs >24 hours after drug administration (median time to onset is 6 days).
- This is thought to occur due to secretory processes caused by the active metabolite of the drug.
- Late onset diarrhea is treated with high dose loperamide and supportive care including fluids if needed.
- Patient should be instructed to take loperamide 4 mg at first sign of diarrhea, followed by 2 mg every 2 hours (4 mg every 4 hours at night) until 12 hours following last bowel movement up to 24 mg/day. Exceeding the daily limit of loperamide 16 mg/day is recommended for treatment of irinotecan-associated diarrhea in adults.
- Atropine has no role in the treatment of late onset diarrhea.

Question 36

Describe the strategy and rationale for management of neutropenia caused by Irinotecan.

Answer 36

The strategy and rationale for management of this condition caused by this drug are:
- A test is available for genotyping of UGT1A1, however, use of the test is not widely accepted as dose reductions are already recommended in patients who have experienced toxicity regardless of genotype.

Question 37

What are the risk factors for developing neutropenia with Irinotecan?

Answer 37

Risk factors for developing this ADR with this drug/class are:
- Homozygous for the UGT1A1*28 allele are at increased risk.
- Heterozygous carriers may also be at increased neutropenic risk, however, most patients have tolerated normal starting doses