Platinum Analogues

Question 1

What drugs are in the Platinum Analogue class?

Answer 1

Drugs in this class are:
- Carboplatin
- Cisplatin
- Oxaliplatin

Question 2

What is the brand name of Carboplatin?

Answer 2

The brand name of this generic drug is:
- Paraplatin

Question 3

What is the brand name of Cisplatin?

Answer 3

The brand name of this generic drug is:
- Platinol

Question 4

What is the brand name of Oxaliplatin?

Answer 4

The brand name of this generic drug is:
- Eloxatin

Question 5

What is the generic of name of Paraplatin?

Answer 5

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

Question 6

What is the generic of name of Platinol?

Answer 6

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

Question 7

What is the generic of name of Eloxatin?

Answer 7

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

Question 8

What are the main indications for use of Carboplatin?

Answer 8

The main indications of this drug are:
- Anal Cancer
- Bladder Cancer
- Breast Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancer
- Hodgkin Lymphoma
- Non-Hodgkin Lymphoma
- NSCLC
- SCLC
- Gynecologic Cancer
- Testicular Cancer

Question 9

What are the main indications for use of Cisplatin?

Answer 9

The main indications of this drug are:
- Anal Cancer
- Bladder Cancer
- Breast Cancer
- Esophageal Cancer
- Gastric Cancer
- Head and Neck Cancer
- Hodgkin Lymphoma
- Non-Hodgkin Lymphoma
- NSCLC
- SCLC
- Gynecologic Cancer
- Testicular Cancer

Question 10

What are the main indications for use of Oxaliplatin?

Answer 10

The main indications of this drug are:
- Esophageal Cancer
- Gastric Cancer
- Non-Hodgkin Lymphoma
- Testicular Cancer
- Biliary Adencocarcinoma
- Colorectal Cancer
- Pancreatic Cancer

Question 11

What is the class and MOA of Carboplatin?

Answer 11

This drug in the following class:
- Platinum Analogues

This drug’s MOA is as follows:
- Alkylating agents which covalently binds to DNA and interfere with the function of DNA by producing interstrand DNA cross-links.
- They preferentially bind to the N-7 position of guanine.

Question 12

What is the class and MOA of Cisplatin?

Answer 12

This drug in the following class:
- Platinum Analogues

This drug’s MOA is as follows:
- Alkylating agents which covalently binds to DNA and interfere with the function of DNA by producing interstrand DNA cross-links.
- They preferentially bind to the N-7 position of guanine.

Question 13

What is the class and MOA of Oxaliplatin?

Answer 13

This drug in the following class:
- Platinum Analogues

This drug’s MOA is as follows:
- Alkylating agents which covalently binds to DNA and interfere with the function of DNA by producing interstrand DNA cross-links.
- They preferentially bind to the N-7 position of guanine.

Question 14

What are the notable monitoring parameters for the Platinum Analogues?

Answer 14

The notable monitoring parameters for this drug class are:
- S/Sx of nephrotoxicity - renal panel
- S/Sx of ototoxicity - consider audiometric and vestibular testing, particularly in all pediatric patients receiving cisplatin (pediatric patients should receive audiometric testing at baseline, prior to each dose, and for several years after discontinuing therapy).
- S/Sx of neuropathy - neurologic evaluation prior to each dose and periodically thereafter

Question 15

What is the emetic potential of Carboplatin?

Answer 15

The emetic potential of this drug is:
- High if AUC >4
- Moderate if AUC <4

Question 16

What is the emetic potential of Cisplatin?

Answer 16

The emetic potential of this drug is:
- High (commonly regarded as the most emetogenic of all chemotherapies)

Question 17

What is the emetic potential of Oxaliplatin?

Answer 17

The emetic potential of this drug is:
- Moderate

Question 18

Describe the emetic potential of the Platinum Analogues.

Answer 18

The emetic potential of this drug class is:
- Moderate (Oxaliplatin, Carboplatin AUC <4) to High (Carboplatin AUC >4, Cisplatin)

Question 19

What drugs in the Platinum Analogue class have a high emetic potential?

Answer 19

Drugs in the class with a high emetic potential are:
- Cisplatin (commonly regarded as the most emetogenic of all chemotherapies)
- Carboplatin if AUC >4

Question 20

What drugs in the Platinum Analogue class have a moderate emetic potential?

Answer 20

Drugs in the class with a moderate emetic potential are:
- Carboplatin if AUC <4
- Oxaliplatin

Question 21

What drugs in the Platinum Analogue class have a low emetic potential?

Answer 21

Drugs in the class with a low emetic potential are:
- None, N/A

Question 22

What drugs in the Platinum Analogue class have a minimal emetic potential?

Answer 22

Drugs in the class with a minimal emetic potential are:
- None, N/A

Question 23

Describe the extravasation risk and management strategies for Oxaliplatin.

Answer 23

The extravasation risk and management strategies for this drug are as follows:
- Irritant with vesicant- like properties
- If extravasation occurs, stop infusion and aspirate. Data conflicts regarding use of warm or cold compresses
- Cold compresses may reduce cellulary injury but could potentially precipitate or exacerbate peripheral neuropathy
- Warm compresses may increase local drug removal but may increase cellular uptake and injury

Question 24

Describe the extravasation risk and management strategies for the Platinum Analogue class.

Answer 24

The extravasation risk and management strategies for this drug class are as follows:
- Carboplatin may be an irritant
- Cisplatin is a vesicant at higher concentrations
- Oxaliplatin is irritant with vesicant like properties

Question 25

Describe the metabolism of the Platinum Analogues.

Answer 25

The metabolism of this drug is as follows:
- Clearance is renal
- The mean AUC of unbound platinum increases as renal function decreases
- 40% increase with mild (CrCl 50 to 80 ml /minute) renal impairment
- 95% increase with moderate (CrCl 30 to 49 ml /minute) renal impairment
- 342% increase with severe (CrCl <30 ml /minute) renal impairment

Question 26

What are the notable ADRs of Carboplatin?

Answer 26

The notable ADRs of this drug are:
- Chronic Peripheral Neuropathy
- Nephrotoxicity
- Hypersensitivity Reactions

Question 27

What are the notable ADRs of Cisplatin?

Answer 27

The notable ADRs of this drug are:
- Ototoxicity
- Chronic Peripheral Neuropathapy
- Nephrotoxicity
- Hypersensitivity Reactions

Question 28

What are the notable ADRs of Oxaliplatin?

Answer 28

The notable ADRs of this drug are:
- Chronic Peripheral Neuropathapy
- Acute Peripheral Neuropathy (unique to oxaliplatin vs other platinums)
- Nephrotoxicity
- Hypersensitivity Reactions

Question 29

What are the notable/common ADRs of the Platinum Analogue class?

Answer 29

The notable/common ADRs of this drug class are:
- Chronic Peripheral Neuropathy (acute is unique to oxaliplatin)
- Nephrotoxicity
- Ototoxicity (cisplatin)
- Hypersensitivity Reactions (especially carboplatin and oxaliplatin)

Question 30

What drug(s) of the Platinum Analogue class is notable for causing electrolyte wasting?

Answer 30

The drugs in this class notable for cause this condition are:
- All can but it is especially notable for Cisplatin

Question 31

What drug(s) of the Platinum Analogue class is notable for causing ototoxicity?

Answer 31

The drugs in this class notable for cause this condition are:
- Cisplatin (especially in children and even moreso in pediatrics)

Question 32

What drug(s) of the Platinum Analogue class is notable for causing acute peripheral neuropathy?

Answer 32

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

Question 33

What drug(s) of the Platinum Analogue class is notable for causing hypersensitivity reactions?

Answer 33

The drugs in this class notable for cause this condition are:
- All can but it is especially notable for Carboplatin and Oxaliplatin

Question 34

Describe the strategy and rationale for management of Peripheral Neuropathy caused by Platinum Analogues.

Answer 34

The strategy and rationale for management of this condition caused by this drug class are:
- This can be broken down into two types: acute and chronic
- Chronic mimics traditional peripheral neuropathy with numbness/tingling in the fingers and toes.
- This can occur >14 days after the dose.
- Can be persistent and interfere with daily activities like writing or walking.
- Symptoms may improve in some patients upon discontinuing treatment.
- Acute is unique to oxaliplatin and presents as cold-induced neuropathy.
- Often occurs within hours of the oxaliplatin infusion and resolves within 7 days.
- Symptoms may include transient paresthesia, dysesthesia, and hypoesthesia (in the hands, feet, perioral area, or throat), jaw spasm, abnormal tongue sensation, or a feeling of chest pressure.
- Patients should be counseled to avoid ice chips, exposure to cold temperatures, and cold food/beverages during or within hours after oxaliplatin infusion.

Question 35

Describe the strategy and rationale for management of nephrotoxicity caused by Platinum Analogues.

Answer 35

The strategy and rationale for management of this condition caused by this drug class are:
- All of the platinum agents have the potential to cause nephrotoxicity.
- Patients should receive aggressive pre and post platinum hydration with normal saline, ideally targeting urine output of 100 ml/hour prior to the chemotherapy infusion.
- Patients also should receive potassium and magnesium replacement as these agents (especially cisplatin) can cause electrolyte wasting.

Question 36

Describe the strategy and rationale for management of ototoxicity caused by Platinum Analogues.

Answer 36

The strategy and rationale for management of this condition caused by this drug class are:
- Cisplatin may cause cumulative and severe ototoxicity.
- Manifested by tinnitus, high-frequency (4,000 to 8,000 Hz) hearing loss, and/or decreased ability to hear normal conversational tones.
- May occur during or after treatment and may be unilateral or bilateral.
- More common in children and even moreso in pediatrics (40%-60%).
- Consider audiometric and vestibular testing, particularly in all pediatric patients receiving cisplatin.

Question 37

Describe the strategy and rationale for management of hypersensitivity reactions caused by Platinum Analogues.

Answer 37

The strategy and rationale for management of this condition caused by this drug class are:
- Platinum agents are the second most common source of hypersensitivity reactions among chemotherapy agents (following asparaginase products).
- Especially common with Carboplatin and Oxaliplatin
- For Carboplatin:
- The incidence of carboplatin hypersensitivity reactions is between 1-44%.
- Most common after 6 -8 doses
- Patients with mild-moderate reactions can be desensitized and may continue to receive infusions
- For Oxaliplatin:
- The incidence of acute reactions is between 12-25% with up to 30% of those being severe infusion reactions.
- Reactions may occur within minutes of drug administration and with any cycle
- Similar to carboplatin, the risk of hypersensitivity reaction is higher with multiple cycles of therapy.
- Patients with mild reactions may be re-challenged.

Question 38

What are the clinical pearls of Carboplatin?

Answer 38

The clinical pearls of this drug are as follows:
- Dosing is based off target AUC (usually 2-6)

Question 39

Describe the use of the Calvert formula.

Answer 39

This use of this formula is as follows:
- Used to calculate Carboplatin dose using target AUC
- Total dose (mg) = Target AUC x (GFR + 25)
- If estimating instead of measuring GFR (as with Cockroft Gault), protocols typically cap GFR at a maximum of 125 ml/minute to avoid potential toxicity (although this does vary per indication)

Question 40

What are the clinical pearls of the Platinum Analogue class?

Answer 40

The clinical pearls of this drug class are as follows:
- They are the second most common source of hypersensitivity reactions among chemotherapy agents (following asparaginase products).