CHEMOTHERAPEUTIC AGENTS

CELL CYCLE DEPENDENCE

        Cell cycle dependent drugs have a killing effect on cells in

a particular phase of the cell cycle

        These drugs are usually anti-metabolites and are most

effective in tumours with a large proportion of actively
dividing cells

        Methotrexate - S-phase

        Mercaptopurine, flurouracil - S-phase

        Vinca alkaloids - M-phase

        Women should be formally assessed by a medical

oncologist for their suitability for chemotherapy. Such
assessment would include FBC, renal and hepatic function
and ECG.

        Drugs used in gynaecological malignancies include

alkylating agents, platinum agents, taxanes, anti-metabolites
(methotrexate) and vinca alkaloids. The side-effect profiles
of these drugs vary but include nausea & vomiting, myelo-
suppression with neutropaenia and risk of sepsis,
neuropathy and long term risk of leukaemia.
        Nausea & vomiting can be reduced by use of 5HT
antagonist ondansetron, H2 antagonists and corticosteroid
        Other side-effects can be monitored by regular FBC, renal
and liver function tests
        No proven mechanisms to reduce the risk of alopecia -
appropriate drug selection

ALKYLATING AGENTS *****

        Form covalent bonds with DNA side chains, causing

depurination, strand breaks and cross-linking.
        Active throughout all phases of the cell cycle; kill both rapidly
and slowly proliferating cells, causing delayed, prolonged and
even permanent bone marrow failure.
        Cause amenorrhoea and oligospermia / azospermia
        Mutagenic and carcinogenic effect on bone marrow,
causing acute myeloid leukaemia - risk related to drug dose
and peak incidence is between 5-10 years post-treatment.
Risk may be as high as 5-10% following treatment for
ovarian cancer

1
 

        Aactive orally

        Drugs include Cyclophosphamide, chlorambucil,

melphalan, treosulfan, ifosfamide *
        Cyclophosphamide * - inactive, converted in liver to active
drug 4-hydroxy-cyclophosphamide. Decomposes within
cells to form phosphoramine mustard (anti-tumour activity)
and acrolein (excreted in urine and responsible for urothelial
toxicity). Less myelotoxic with lower risk of leukaemia
compared to other alkylating agents. Associated with acute
haemorrhagic cystitis (as with its analogue ifosfamide) - can
be prevented by maintaining high urine out-put or by the co-
administration of N-acetylcysteine or mesna - neutralise
acrolein.
        Other side effects include reversible alopecia, darkened
skin and nails, pneumonitis and pulmonary fibrosis; renal
failure.