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Cytotoxic Antibiotics

Cytotoxic antibiotics are used very commonly and widely in many malignancies.

Members

Bleomycin, daunorubicin, doxorubicin, dactinomycin, epirubicin, idarubicin, mitoxantrone and mitomycin.

Method of Action

Direct toxic action on cellular DNA.1

Important interactions of the group
  • Some cytotoxic antibiotics can react with radiotherapy enhancing the toxic effect.
  • Irreversible cardiotoxicity of this group means it must be used cautiously in patients with previous cardiac illness.2
  • Trastuzumab enhances the risk of cardiac toxicity.
Doxorubicin

Inhibits both DNA and RNA synthesis. It is associated with cardiotoxicity and severe skin reactions. Therefore, a liposomal formulation of doxorubicin is available which reduces the cardiotoxicity, but the skin reactions are still a problem.

Indications

  • Solid tumours e.g. bladder, gastric, pancreatic and oesophageal
  • Acute leukaemias
  • Lymphomas
  • Breast cancer

NICE guidance3

  • NICE guidance advises the use of pegylated liposomal doxorubicin hydrochloride (PLDH) in ovarian cancer patients who are allergic to platinum based compounds.
  • It is also recommended as a second line in ovarian cancer that is partially platinum-sensitive, platinum resistant or platinum refractory.
  • PLDH is also recommended following relapse after second-line chemotherapy and platinum based compounds.4

Cautions and contraindications

  • Patients with a cardiac history - total cumulative dose of doxorubicin limited to 450 mg/m2.
  • Liver impairment.
  • Phenytoin absorption is impaired - increased risk of seizures.
  • Increased risk of ciclosporin toxicity.

Initiation

  • Doxorubicin is given at 3 weekly interval via a continuous intravenous infusion.
  • It can also be instilled via the bladder for carcinoma of the bladder.

Side effects

  • Myelosuppression - usually occurs at 2 -4 weeks with complete recovery by 8 weeks.5
  • Extravasation causes severe skin necrosis.
  • Excreted in bile, therefore, need to monitor bilirubin levels - if high then need dose reduction.
  • Associated with cardiac toxicity - this is rare and includes SVT and cardiomyopathies (related to dose).
  • Red, painful skin (palmar plantar erythrodysesthesia) rash may develop on the hands and feet with the liposomal formulations called "Hand-foot syndrome". This can be reduced by lower doses and avoiding tight fitting gloves and socks.6
Bleomycin
  • Used in metastatic germ cell tumours and non-Hodgkin's lymphoma.
  • Can be given intravenously or intramuscularly
  • Myelosuppression is rare.
  • Causes pigmentation of the flexures, mucositis and Raynaud's phenomenon.
  • May cause hypersensitivity - occasionally hydrocortisone is given prior to administration.
  • Progressive pulmonary fibrosis with lung crepitations (usually bibasal) or CXR changes may occur which is dose related and an indication for therapy to stop.
Mitomycin
  • Leads to production of an alkylating metabolite.
  • Delayed bone marrow toxicity is seen at 6 weeks.
  • Can cause renal impairment.
  • Pulmonary fibrosis is also seen occasionally.7
Other members

Cytotoxic antibiotics are similar to doxorubicin in terms of toxicity, cautions and contraindications. However, there are a few differences.

  • Epirubicin - similar to doxorubicin.
  • Idarubicin - can also be given orally.
  • Daunorubicin - is also used in Kaposi's sarcoma.
  • Mitoxantrone - used in metastatic breast cancer, lymphoma and leukaemia.
  • Dactinomycin - used in paediatric neoplasms.
  • Mitomycin - used intravenously and intravesically. Can lead to lung fibrosis and renal impairment.

Document References
  1. American Cancer Society; What are the different types of chemotherpy drugs? Apr 2005
  2. Safra T; Cardiac safety of liposomal anthracyclines.; Oncologist. 2003;8 Suppl 2:17-24. [abstract]
  3. NICE; Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for the treatment of advanced ovarian cancer; May 2005.
  4. Thigpen JT, Aghajanian CA, Alberts DS, et al; Role of pegylated liposomal doxorubicin in ovarian cancer.; Gynecol Oncol. 2005 Jan;96(1):10-8. [abstract]
  5. Rang, H.P., Dale, M.M., Ritter, J.M. and Moore, P.K. (2003) Pharmacology, 5th ed, Bath, Churchill Livingstone.
  6. Hussein M; Pegylated liposomal doxorubicin, vincristine, and reduced-dose dexamethasone as first-line therapy for multiple myeloma.; Clin Lymphoma. 2003 Aug;4 Suppl 1:S18-22. [abstract]
  7. British National Formulary British Medical Association and Royal Pharmaceutical Society of Great Britain. London.
Internet and Further Reading AcknowledgementsEMIS is grateful to Dr Gurvinder Rull for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2007.
DocID: 310
Document Version: 1
DocRef: bgp25224
Last Updated: 2 Oct 2007
Review Date: 1 Oct 2008
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