Important note: Information in this article was accurate in September 2000. The state of the art may have changed since the publication date.
Although hydroxyurea (HU) may be falling out of favour as an anti-HIV treatment, it may yet be useful as a treatment for some AIDS-related cancers. Researchers in Memphis Tennessee have been conducting experiments on EBV-infected cells that turn into tumours. According to their results, HU can stop the growth of EBV driven cancer cells. The drug appears to work by cleansing the cells of EBV's genetic material. After this happens the tumours stop growing. Stimulated by these promising lab results, doctors designed a low-dose regimen of HU for EBV-related brain cancers called PCNSL (primary central nervous system lymphoma). They recently reported results from two patients with AIDS.
One patient was a 13-year old girl whose symptoms included problems walking, weak muscle control on the left side of her body and blindness in her left eye. Her CD4+ count was 3 cells/ml . CAT and magnetic (MRI) scans of her brain revealed a large tumour in the right part of her brain. Surgery did not stop the growth of the tumour so doctors gave her HU 400 mg/ square meter of skin/day for four weeks. Despite use of HU the tumour did not shrink so doctors increased her dose to 700 mg/square meter of skin/day.
After two months her muscle strength improved and by the 4th month her vision, reflexes and ability to walk also improved. By the 7th month her tumour had greatly shrunk and her CD4+ count reached 11 cells. The girl survived for two years after her cancer diagnosis and recently died from complications not related to lymphoma.
The second patient was a 37-year old male who had muscle weakness on the left side of his body. Magnetic scans revealed a tumour on the right part of his brain. He had no detectable CD4+ cells. Despite radiation and chemotherapy the tumour only decreased slightly. Doctors next tried HU 550 mg/square meter of skin/day for four weeks.
A year after he first sought help his muscle strength has improved as has his ability to walk. His CD4+ count rose to 12 cells. Two years later he is still alive and the tumour, although present, is not growing.
In both of these cases the symptoms caused by the brain tumours were the first indicator that these people were infected with HIV.
Although both patients received HAART, their viral loads "remained high", according to the doctors. As well their CD4+ cell counts were never elevated for long. This probably rules out a major benefit from HAART in these two people.
The dose of HU used was too low to have significant direct anti-cancer activity. So it appears that recovery in both cases was due to HU's anti-EBV effect.
Further research into the use of HU for the treatment of EBV-related cancers is underway at St Jude Children's Research Hospital, Memphis, Tennessee.
1. Maggiorella MT, Monardo F, Koanga-Mogtomo ML, et al.Detection of Infectious Simian Immunodeficiency Virus in B- and T-Cell Lymphomas of Experimentally Infected Macaques. Blood 1998 May 1;91(9):3103-11.
2. Chodosh J, Holder BP, Gan Y-J, et al. Eradication of latent Epstein-Barr Virus by hydroxyurea alters the growth-transformed phenotype. J Infect Dis 1998 May;177(5):1194-201.
3. Slobod KS, Tyalor GHT, Sandlund JT, et al. Epstein-Barr virus-targeted therapy for AIDS-related primary lymphoma of the central nervous system. Lancet 2000 Oct 28;356(9240):1493-4.
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