Considerable efforts have been made to improve the efficacy of interferon alfa in patients with chronic hepatitis C. Currently used regimens, including long-term interferon alfa alone or in combination with ribavirin, produce a sustained response rate of 40-50%. Other possibly effective strategies include a longer duration of treatment, higher fixed doses, and high-dose induction (2). A longer duration of treatment has been evaluated in patients with chronic hepatitis B. In 118 patients, treatment for 32 rather than 16 weeks enhanced the virological response to hepatitis B without increasing the severity of adverse effects, except for hair loss, which was more frequent during prolonged therapy (3).
A wide range of persistent symptoms has been reported during interferon alfa treatment for chronic hepatitis C. An analysis of 222 patients from the USA and France, enrolled in a multicenter trial, suggested that pretreat-ment symptoms were an important predictor of moderate or severe (defined as debilitating) adverse effects during treatment with interferon alfa (4). Compared with baseline, the incidences of moderate and severe fatigue, myalgia, arthralgia, headache, dry eyes, and dry mouth increased significantly after 6 months. In each case, the development of these debilitating adverse effects was associated with the presence of that symptom at baseline. They were more often reported in patients who received interferon alfa daily than three times weekly, and in US than French patients, suggesting possible differences in cultural attitudes toward illness. There was also increased use of antidepressants during the 6-month survey.
Low daily doses of interferon alfa have been used with small doses of cytarabine in the treatment of early chronic myelogenous leukemia (5). With doses sufficient to obtain a good cytogenetic response (for example 3.7 MU/m2/day plus cytarabine 7.5 mg/day) toxicity was considered acceptable. There was significant fatigue in 43% of cases, significant neurological changes in 27%, weight loss in 19%, and oral ulcers in 4%.
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