Alkylating Agents Flashcards
Name the 4 classes of alkylating agents. Are they cell cycle specific?
Nitrogen mustards, nitrosureas, triazenes, platinums. CCNS
Name the 3 nitrogen mustards. Which one can undergo spontaneous activation without going through the liver?
Mechlorethamine, cyclophosphamide, ifosfamide. Mechlorethamine can undergo spontaneous conversion to an active form.
Name the 2 nitrosureas.
Carmustine, lomustine
Name the 2 triazenes. Which one can be taken orally?
Dacarbazine, temozolomide. Temozolomide is taken orally and has good oral bioavailability.
Name the 3 platinum analogs. How are they activated and where do they commonly bind?
Cisplatin, carboplatin, oxaliplatin. They activate by reacting with water and bind to DNA guanine N7.
Which alkylating agents have the longest half lives? How long?
Cyclophosphamide and Ifosfamide, 7-15 hours
Which alkylating agent is always given via IV? What subclass does it belong to?
Dacarbazine - triazene
Name 4 alkylating agents that are activated by cytochrome P450 in the liver.
Mechlorethamine, cyclophosphamide, ifosfamide, and dacarbazine.
Which subclass of alkylating agents are used to treat brain tumors? What makes them so good for treating CNS problems?
The nitrosureas (carmustine and lomustine); they are lipid-soluble/lipophilic so can cross the BBB.
Which alkylating agent is often used in combination regimens, as well as for testicular, ovarian, cervical, and bladder cancers?
Cisplatin (platinum analog)
What cancer is carboplatin approved to treat?
Ovarian
What 2 cancers is oxaliplatin used to treat?
Gastric and colorectal
Alkylating agent for colorectal cancer that can cause peripheral neuropathies?
Oxaliplatin (platinum analog)
Name three organs that cisplatin causes side effects in (besides nausea/vomiting and myelosuppression)
Kidneys, ears, peripheral nerves
Which alkylating agent is used to treat malignant gliomas?
Temozolomide (triazene)
What are two significant side effects of the nitrosureas?
Renal toxicity and pulmonary fibrosis
Which 2 alkylating agents are used to treat Hodgkin’s disease, as well as cutaneous cancers?
Mechlorethamine, dacarbazine
Which alkylating agent has fallen out of fashion because it causes sterility?
Mechlorethamine
What is the most widely used alkylating agent, especially for blood, breast, ovarian, and lung cancers?
Cyclophosphamide
Which hematologic cancers is cyclophosphamide used to treat?
ALL, CLL, non-Hodgkins lymphoma
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?
Hemorrhagic cystitis (local bladder irritation) treated by hydration and MESNA (sodium 2-mercaptoethane sulfonate) administration
What is the nitrogen mustard ifosfamide typically used to treat?
Sarcomas and testicular cancer
How is temozolomide activated in the body?
Nonenzymatic conversion at physiologic pH
What cancers is dacarbazine used to treat, and which combination regimen does it belong to?
Hodgkin’s disease and malignant melanoma, ABVD for Hodgkin’s
