Alkylating Drugs (Cancer Therapy)

Alkylating agents have been around since the 1940's and are still valuable and widely used in chemotherapy. They work on all phases of the cell cycle and interfere with DNA synthesis preventing tumour cells dividing.¹

• Chronic leukaemias (cyclophosphamide, chlorambucil, busulfan and mitobronitol)
• Non-Hodgkin's Lymphoma (cyclophosphamide, chlorambucil)
• Hodgkin's disease (lomustine, chlorambucil)
• Recurrent glioblastoma multiforme (carmustine)
• Multiple myeloma (melphalan, carmustine)
• Prostate cancer (estramustine - a combination of oestrogen and chlormethine)
• Lung, breast and ovarian cancers(cyclophosphamide, melphalan, treosulfan)
• Polycythaemia vera (melphalan)

• Renal impairment
• Hepatic impairment
• Porphyria

• Pregnancy
• Breast feeding

• Nausea and vomiting - cyclophosphamide is moderately emetogenic and lomustine has severe emetogenic.
• Skin rashes - especially with chlorambucil.
• Extravasation of intravenous compounds.
• Gametogenesis severely affected - always consider pre-treatment discussion about fertility.³
• Prolonged use associated with increase in incidence of acute non-lymphocytic leukaemia. (More likely when used with irradiation).

Cyclophosphamide

• Used in chronic lymphocytic leukaemia, lymphomas, soft-tissue and osteogenic and solid tumours.
• Inactive, until metabolised by liver.
• One metabolite that is excreted in the urine (acrolein) can cause haemorrhagic cystitis - thus plenty of fluids advised for two days after therapy.
• If high doses given then mesna can be given to reduce haemorrhagic cystitis.
• Also used in auto-immune conditions e.g. rheumatoid arthritis, nephrotic syndrome (unlicensed).
• Ifosfamide is a related compound which is also given with mesna to reduce urothelial toxicity.

Chlorambucil

• Used in haematological malignancies including chronic lymphocytic leukaemia, non-Hodgkins lymphoma, Hodgkins disease and Waldenstrom's macroglobulinaemia.
• Bone marrow suppression and rashes are common and can include Stevens-Johnson syndrome.

Busulfan

• Used in Chronic myeloid leukaemia and prior to stem-cell transplantation.
• Can cause irreversible bone marrow suppression - thus need careful and regular monitoring of blood counts.²
• Rarely cause progressive pulmonary fibrosis.
• Oral busulfan is associated with skin hyperpigmentation.

For full indications, cautions, contra-indications and side effects see individual drug monographs