Alkylating Agents

Question 1

Name the 4 classes of alkylating agents. Are they cell cycle specific?

Answer 1

Nitrogen mustards, nitrosureas, triazenes, platinums. CCNS

Question 2

Name the 3 nitrogen mustards. Which one can undergo spontaneous activation without going through the liver?

Answer 2

Mechlorethamine, cyclophosphamide, ifosfamide. Mechlorethamine can undergo spontaneous conversion to an active form.

Question 3

Name the 2 nitrosureas.

Answer 3

Carmustine, lomustine

Question 4

Name the 2 triazenes. Which one can be taken orally?

Answer 4

Dacarbazine, temozolomide. Temozolomide is taken orally and has good oral bioavailability.

Question 5

Name the 3 platinum analogs. How are they activated and where do they commonly bind?

Answer 5

Cisplatin, carboplatin, oxaliplatin. They activate by reacting with water and bind to DNA guanine N7.

Question 6

Which alkylating agents have the longest half lives? How long?

Answer 6

Cyclophosphamide and Ifosfamide, 7-15 hours

Question 7

Which alkylating agent is always given via IV? What subclass does it belong to?

Answer 7

Dacarbazine - triazene

Question 8

Name 4 alkylating agents that are activated by cytochrome P450 in the liver.

Answer 8

Mechlorethamine, cyclophosphamide, ifosfamide, and dacarbazine.

Question 9

Which subclass of alkylating agents are used to treat brain tumors? What makes them so good for treating CNS problems?

Answer 9

The nitrosureas (carmustine and lomustine); they are lipid-soluble/lipophilic so can cross the BBB.

Question 10

Which alkylating agent is often used in combination regimens, as well as for testicular, ovarian, cervical, and bladder cancers?

Answer 10

Cisplatin (platinum analog)

Question 11

What cancer is carboplatin approved to treat?

Answer 11

Ovarian

Question 12

What 2 cancers is oxaliplatin used to treat?

Answer 12

Gastric and colorectal

Question 13

Alkylating agent for colorectal cancer that can cause peripheral neuropathies?

Answer 13

Oxaliplatin (platinum analog)

Question 14

Name three organs that cisplatin causes side effects in (besides nausea/vomiting and myelosuppression)

Answer 14

Kidneys, ears, peripheral nerves

Question 15

Which alkylating agent is used to treat malignant gliomas?

Answer 15

Temozolomide (triazene)

Question 16

What are two significant side effects of the nitrosureas?

Answer 16

Renal toxicity and pulmonary fibrosis

Question 17

Which 2 alkylating agents are used to treat Hodgkin’s disease, as well as cutaneous cancers?

Answer 17

Mechlorethamine, dacarbazine

Question 18

Which alkylating agent has fallen out of fashion because it causes sterility?

Answer 18

Mechlorethamine

Question 19

What is the most widely used alkylating agent, especially for blood, breast, ovarian, and lung cancers?

Answer 19

Cyclophosphamide

Question 20

Which hematologic cancers is cyclophosphamide used to treat?

Answer 20

ALL, CLL, non-Hodgkins lymphoma

Question 21

What is a common side effect caused by the nitrogen mustards cyclophosphamide and ifosfamide (due to their toxic metabolite acrolein), and how is it ameliorated?

Answer 21

Hemorrhagic cystitis (local bladder irritation) treated by hydration and MESNA (sodium 2-mercaptoethane sulfonate) administration

Question 22

What is the nitrogen mustard ifosfamide typically used to treat?

Answer 22

Sarcomas and testicular cancer

Question 23

How is temozolomide activated in the body?

Answer 23

Nonenzymatic conversion at physiologic pH

Question 24

What cancers is dacarbazine used to treat, and which combination regimen does it belong to?

Answer 24

Hodgkin’s disease and malignant melanoma, ABVD for Hodgkin’s

Question 25

Which subclass of alkylating agents does not form carbonium or ethyleneimonium ion intermediates with DNA?

Answer 25

the platinum analogs

Question 26

What alkylating agent is used topically to treat cutaneous T-cell lymphoma, as well as Hodgkin’s disease?

Answer 26

Mechlorethamine