Ketoconazole prophylaxis in patients with solid tumours receiving aggressive immunosuppressive therapy. An open randomized comparison between 200 mg/d and 400 mg/d doses

Abstract

Forty-three patients, most with solid tumours, were included in a study comparing the antifungal prophylactic effect of ketoconazole (Nizoral; Janssen) 200 mg/d and 400 mg/d during the period of immunosuppressive therapy. Seven patients were not seen for follow-up and 6 died of their underlying disease without clinical evidence of mycosis. Twelve of the patients who could be evaluated received ketoconazole 200 mg/d and 18 received 400 mg/d. No infections occurred during the period of prophylactic treatment. In the group receiving 200 mg/d 10 of 36 cultures (28%) were positive for Candida albicans before prophylaxis. During prophylaxis 5 of 18 cultures (28%) were positive and at the end of the prophylactic regimen 1 out of 37 cultures (3%) was positive. In the 400 mg/d group, 13 of 47 cultures (28%) were positive at the start, 2 out of 20 (10%) were positive during prophylaxis and 1 out of 45 (2%) was still positive at the end. The drug was clinically well tolerated. Twenty of the 30 evaluable patients had no significant biochemical abnormalities, 5 had an increased serum transaminase level, 2 had an increased alkaline phosphatase level, and 3 had combined increases of serum transaminase and alkaline phosphatase levels. These abnormalities are regularly seen in patients with metastatic malignant disease, and are not necessarily related to the ketoconazole prophylaxis.