Security and maximal tolerated doses of fluvastatin in pediatric cancer patients

Background. The role of cholesterol in neoplasic cell growth and its inhibi tion by drugs has recently been studied. Cholesterol biosynthesis inhibitor s have been used as adjuvants in the treatment of cancer and possibly as pr ophylactic in carcinogenesis. Objective. The objective of the study was to determine the maximal tolerate d doses (MTD) and toxic effects of fluvastatin in pediatric cancer patients . Methods. This study was carried out in a third level Social Security Hospit al in Mexico City, We included pediatric patients from April 1996 to May 19 97. All were terminal cancer patients who did not respond to conventional t herapies. Fluvastatin was given p.o. at doses of 2 mg/kg/day for 14 days ev ery 4 weeks in three patients. Subsequent cohorts of three patients each ha d increments of 2 mg/kg/day of the drug until maximal tolerated doses were found. Toxic effects of the drug were evaluated by physical exploration, la boratory assays and a questionnaire given to each patient. Results. Twelve patients were included. Diagnoses included two osteosarcoma s, eight central nervous system tumors, one lung tumor, and one Ewing's sar coma, Ten patients died within 1 to 18 months. Two are alive 22 months afte r inclusion into the study, both with anaplasic astrocytoma, A total of 27 courses were administered. The MTD was 8 mg/kg/day, Toxic effects were inso mnia, nausea, vomiting, abdominal distention and myalgias. Toxicity was dos e-dependent. Laboratory assays demonstrated no significant changes during t reatment. Conclusions. Fluvastatin can be safely used at doses of 8 mg/kg/day in pedi atric patients with cancer. This dose should be used in additional trials. (C) 1999 IMSS. Published by Elsevier Science Inc.