Hydroxycarbamide (Hydroxyurea)

Hydroxycarbamide was previously known as hydroxyurea. It is chemotherapy that is given as a treatment for some types of cancer.

• Hydroxyurea alters the cellular enzyme ribonucleotide reductase.
• The body uses ribonucleotide reductase to produce proteins called dNTPs which are normally used as building blocks to make DNA.

It is most commonly used to treat chronic myeloid leukaemia.
It is also used in:

• Melanoma
• Ovarian cancer
• Primary squamous cell carcinoma of the head and neck (excluding the lip)
• Sickle cell anaemia
• Psoriasis

Hydroxyurea is also used to treat essential thrombocythaemia,¹ polycythaemia vera, hypereosinophilic syndrome, lung cancer and a variety of other cancers. In addition, hydroxyurea has been used along with anti-infective and surgical therapy to treat chronic urinary tract infections caused by certain bacteria.

The Scotland Leukaemia Registry audit of chronic myeloid leukaemia in 1999 and 2000 identified 64 new cases of CML.

• These figures suggest an incidence 0.64/100,00/yr.
• For first line therapy 56% of patients received hydroxyurea with, or without interferon.²
• A randomised controlled trial in 2004 did not find any difference between hydroxyurea and busulfan treatment, either in overall survival or in blast crisis free survival. (Blast crisis is the final phase in the evolution of CML, and behaves like an acute leukaemia, with rapid progression and short survival.) However, transplanted patients survived significantly longer than non-transplanted patients.³

Hydroxyurea therapy can ameliorate the clinical course of sickle cell anaemia in some adults with three or more painful crises per year.⁴

• It inhibits sickling by increasing levels of fetal haemoglobin. This might decrease the frequency of painful crises.
• Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect.
• The beneficial effects of hydroxyurea do not become manifest for several months, and its use must be carefully monitored.
• The long-term safety of hydroxyurea in patients with sickle cell anaemia is uncertain.

An important efficacy multicentre trial of hydroxyurea in 299 adults with sickle cell anaemia, showed that hydroxyurea reduced by nearly half the frequency of hospitalisations and the incidence of pain, acute chest syndrome, and blood transfusion.⁵ A modest improvement in general perceptions of health and social function and recall of pain was found.
Hydroxyurea does not appear to prevent the cerebrovascular complications of sickle cell anaemia. However, in children aged 5 to 15 years, without a history of overt CVA and with more than three painful episodes yearly, hydroxyurea maintained their cognitive performance compared with their sibling controls, whereas performance was noted to deteriorate in untreated patients.⁶
While hydroxyurea appears both effective and safe in severely affected adults over a two-year period, further studies are required to elucidate its role for other patients.

Hydroxyurea is a second line treatment for psoriasis.⁷ It has been used since 1965.

• It is only used when other second line agents have failed or are contraindicated.
• It is generally considered to be effective although there is only one (low powered) controlled trial of its use.^8,9
• Hydroxyurea avoids the hepatotoxicity associated with methotrexate and the nephrotoxicity associated with ciclosporin. It can therefore often be useful when other drugs are contraindicated, although it should be avoided, if possible when renal function is markedly impaired.
• The main hazard is myelosuppression and careful monitoring of the full blood count is required. It is recommended prior to treatment and weekly for the first 6 weeks.
• Treatment selection must take into account both the patient's disease severity and expectations for improvement, as well as the risk-benefit ratio associated with each potential therapy.¹⁰

• Hydroxyurea may interfere with the normal menstrual cycle in women and may stop sperm production in men:
  • However sterility should not be assumed and a reliable method of birth control should be used.
  • It may harm the fetus, although pregnancy has been reported in at least 16 women receiving hydroxyurea without adverse outcomes.
• Long-term effects of hydroxyurea are still not defined:
  • Studies of hydroxyurea in patients with myeloproliferative disorders suggest that in this unique setting about 10% of patients treated with hydroxyurea develop acute leukemia.^11,12
  • There are reports of sickle cell patients treated with hydroxyurea who have developed leukaemia.
  • Even with a small risk of leukemogenesis, the benefits of this treatment in seriously ill patients predominate.
• Adverse effects on growth and development have not been reported:¹³
  • It is not yet known whether continued drug exposure starting at a very young age will be especially hazardous or beneficial.