Alkylating Agents (kursiv)

Cytotoxic agents

Cyclophosphamide

Alkylating agents —> further subgroup: Oxazaphosphorines

• Alkylation of DNA/RNA → cross-links DNA at guanine N–7 → ↓ DNA replication

• Cyclophosphamide and ifosfamide require activation in the liver.

• Active metabolites interfere with growth of rapidly proliferating malignant cells. 

• Polyfunctional alkylating agent, may cross-link DNA, interfering with DNA replication and transcription of RNA, disrupting nucleic acid function. 

• Also has potent immunosuppressive activity. 

• The drug exhibits phosphorylating properties that also enhance its cytotoxicit

• Malignancies

  • Solid tumors (e.g., breast cancer, ovarian cancer, small cell lung cancer)

  • Leukemias

  • Lymphomas

  • Multiple myeloma

• Nonneoplastic conditions

  • Autoimmune diseases (e.g., systemic lupus erythematosus, granulomatosis with polyangiitis)

  • Nephrotic syndrome

• Bladder toxicity: metabolism of oxazaphosphorines produces the urotoxic substance acrolein

  • Hemorrhagic cystitis: inflammation of the bladder, damaging to the epithelium and blood vessels

  • Bladder carcinoma

• Myelosuppression

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

• Pulmonary toxicity

• Cardiac toxicity

• Infertility

• Fanconi syndrome (ifosfamide)

• Neurotoxicity (ifosfamide)

• Hodgkins Disease

• Non-Hodkins Lymphoma

• Multiple Myeloma

• Leukemias (particulary CLL)

• Cutaneous T-cell Lymphoma

• Neuroblastoma

• Ovarian Cancer

• Retinoblastoma

• Breast Cancer

• Small cell lung cancer

• Sarcomas

• Nephrotic Syndrome

• Renal/Hepatic/Cardiac/Bone marrow transplantation (—> as immunosuppressant)

• Severely depressed bone marrow function. 

• Known hypersensitivity to cyclophosphamide or any ingredient in the formulation.

Leukopenia, anorexia, nausea, vomiting, sterile hemorrhagic cystitis, alopecia.