Overview Alkylating Agents Mechanism of Action Cyclophosphamide and ifosfamide Crosslinks DNA Hemorrhagic cytitis and myelosupression Nitrosoureas Crosslinks DNA Dizziness and ataxia Busulfan Alkylates DNA Pulmonary fibrosis and hyperpigmentation Cyclophosphamide and Ifosfamide Mechanism covalently crosslinks DNA at guanine N7 position between strands and within strands requires bioactivation by liver Clinical use non-Hodgkin's lymphoma breast cancer ovarian cancer immunosuppression Toxicity hemorrhagic cystitis prevent with mesna or N-acetylcysteine thiol group binds acrolein, a toxic metabolite myelosuppression Nitrosoureas (Carmustine, Lomustine, Semustine, and Streptozocin) Mechanism crosslinks DNA crosses BBB and enters CNS requires bioactivation Clinical use brain tumors including glioblastoma multiforme Toxicity CNS toxicity dizziness ataxia Busulfan Mechanism alkylates DNA Clinical use CML was gold standard before imatinib was discovered hematopoietic stem cell transplants used for bone marrow ablation Toxicity pulmonary fibrosis hyperpigmentation