BACKGROUND: The role of cholesterol in neoplasic cell growth and its inhibition by drugs has recently been studied. Cholesterol biosynthesis inhibitors have been used as adjuvants in the treatment of cancer and possibly as prophylactic in carcinogenesis. OBJECTIVE: The objective of the study was to determine the maximal tolerated doses (MTD) and toxic effects of fluvastatin in pediatric cancer patients. METHODS: This study was carried out in a third level Social Security Hospital in Mexico City. We included pediatric patients from April 1996 to May 1997. All were terminal cancer patients who did not respond to conventional therapies. Fluvastatin was given p.o. at doses of 2 mg/kg/day for 14 days every 4 weeks in three patients. Subsequent cohorts of three patients each had 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, laboratory assays and a questionnaire given to each patient. RESULTS: Twelve patients were included. Diagnoses included two osteosarcomas, eight central nervous system tumors, one lung tumor, and one Ewing's sarcoma. Ten patients died within 1 to 18 months. Two are alive 22 months after 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 insomnia, nausea, vomiting, abdominal distention and myalgias. Toxicity was dose-dependent. Laboratory assays demonstrated no significant changes during treatment. CONCLUSIONS: Fluvastatin can be safely used at doses of 8 mg/kg/day in pediatric patients with cancer. This dose should be used in additional trials.
BACKGROUND: The role of cholesterol in neoplasic cell growth and its inhibition by drugs has recently been studied. Cholesterol biosynthesis inhibitors have been used as adjuvants in the treatment of cancer and possibly as prophylactic in carcinogenesis. OBJECTIVE: The objective of the study was to determine the maximal tolerated doses (MTD) and toxic effects of fluvastatin in pediatric cancerpatients. METHODS: This study was carried out in a third level Social Security Hospital in Mexico City. We included pediatric patients from April 1996 to May 1997. All were terminal cancerpatients who did not respond to conventional therapies. Fluvastatin was given p.o. at doses of 2 mg/kg/day for 14 days every 4 weeks in three patients. Subsequent cohorts of three patients each had 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, laboratory assays and a questionnaire given to each patient. RESULTS: Twelve patients were included. Diagnoses included two osteosarcomas, eight central nervous system tumors, one lung tumor, and one Ewing's sarcoma. Ten patients died within 1 to 18 months. Two are alive 22 months after 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 insomnia, nausea, vomiting, abdominal distention and myalgias. Toxicity was dose-dependent. Laboratory assays demonstrated no significant changes during treatment. CONCLUSIONS:Fluvastatin can be safely used at doses of 8 mg/kg/day in pediatric patients with cancer. This dose should be used in additional trials.
Authors: Jordan M Thompson; Alejandro Alvarez; Monika K Singha; Matthew W Pavesic; Quy H Nguyen; Luke J Nelson; David A Fruman; Olga V Razorenova Journal: Mol Cancer Ther Date: 2018-05-02 Impact factor: 6.261
Authors: Wesley Y Yu; Sheena T Hill; E Ricky Chan; John J Pink; Kevin Cooper; Sancy Leachman; Amanda W Lund; Rajan Kulkarni; Jeremy S Bordeaux Journal: J Invest Dermatol Date: 2021-01-06 Impact factor: 7.590
Authors: Elizabeth de Wolf; Marwan Ibrahim Abdullah; Stefanie M Jones; Karen Menezes; Darren M Moss; Falko P Drijfhout; Sarah R Hart; Clare Hoskins; Euan A Stronach; Alan Richardson Journal: Sci Rep Date: 2017-07-14 Impact factor: 4.379