Alkylating Agents Flashcards
Mechlorethamine
Class: Nitrogen mustard
Mechanism: Activated spontaneously in body fluids or activated enzymatically in the liver
Therapeutic uses: Hodgkin’s lymphoma
Topically for cutaneous T-cell lymphoma
Toxicity: severe nausea/vomiting, myelosuppression (leukopenia, thrombocytopenia)
Other: Do not use much anymore due to sterility
Cyclophosphamide
Class: Nitrogen mustard
Mechanism: Activated enzymatically in the liver by P450 into phosphamide mustard.
Therapeutic uses: ALL, non-Hodgkin’s lymphoma, breast, lung, ovarian
Toxicity: Hemorrhagic cystitis (local irritation in the bladder due to toxic drug metabolites (acrolein) in the urine)
Adequate hydration and administration of MESNA minimizes this problem.
Other: Relatively long half-life, taken orally
Ifosfamide
Class: Nitrogen mustard
Mechanism: Activated enzymatically in the liver by p450 into phophamide mustard.
Therapeutic uses: Sarcoma, Testicular cancer
Toxicity: Hemorrhagic cystitis (local irritation in the bladder due to toxic drug metabolites (acrolein) in the urine)
Adequate hydration and administration of MESNA minimizes this problem.
Relatively long half-life, taken orally
Carmustine
Class: Nitrosoureas
Mechanisms: Alkylating agent.
Therapeutic uses: Lipid soluble and therefore able to cross BBB and treat brain tumors.
Toxicity: Renal toxicity and pulmonary fibrosis.
Lomustine
Class: Nitrosoureas
Mechanism: Alkylating agent.
Therapeutic uses: Lipid soluble and therefore crosses the BBB and treats brain tumors
Toxicity: Renal toxicity and pulmonary fibrosis.
Dacarbazine
Class: Triazenes
Mechanism: Alkylating agent that is a prodrug and activated by cytochromes of liver.
Therapeutic uses: Hodgkin’s, melanoma
Toxicity: Flu-like symptoms
Other: IV administration
Procarbazine
Class: Triazenes
Mechanism: Alkylating agent that forms free radicals
Therapeutic uses: Hodgkin’s
Toxicity: May cause leukemia.
Temozoline
Class: Triazenes
Mechanism: Non-enzymatic conversion to methylhydrazine at physiological pH.
Therapeutic uses: Malignant gliomas
Toxicity: Flu-like symptoms
Other: taken orally
Cisplatin
Class: Platinum Analogs
Mechanism: Alkylating agents except do not formally alkylate via carbonium ion intermediate instead they are converted to active form by interacting with water and then bind to the nucleophilic sites on DNA to form intrastrand and interstrand crosslinks.
Therapeutic uses: testicular, ovarian, cervical, bladder, head and neck, lung.
Toxicity: Nephrotoxicity (limits dose), Ototoxicity, peripheral sensory and motor neuropathies at high doses.
Carboplatin
Class: Platinum Analog
Mechansim: Alkylating agents except do not formally alkylate via carbonium ion intermediate but rather are converted to active form by interacting with water and then bind to nucleophilic sites on DNA to form intrastrand and interstrand crosslinks.
Therapeutic uses: Ovarian
Toxicity: Only myelosuppression (thrombocytopenia)
Oxaliplatin
Class: Platinum Analog
Mechanism: Alkylating agents except do not formally alkylate via carbonium ion intermediate but rather are converted to active form by interacting with water and then bind to nucleophilic sites on DNA to form intrastrand and interstrand crosslinks.
Therapeutic uses: Gastric and colorectal cancer
Toxicity: cold induced sensory peripheral neuropathy, neutropenia
