Security and maximal tolerated doses of fluvastatin in pediatric cancer patients

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. objetive. The objetive 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 thirid 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 give p.o. at doses of 2 mg/kg/day dor 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 aolive 22 months after inclusion into the study, both with anaplasic astrocytoma. A total of 27 courses wer administered. The MTD was 8 mg/kg/day. Toxic effects were insomnia, nausea, vomiting, abdominal distention and myalgias. Txocicity 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

Survival of patients with Medulloblastoma treated with carboplatin and etoposide before and after radiotherapy

Background. Medulloblastoma represents 20 percent of all tumors of the central nervous system. Patients with partial resection of the tumor and those with extension into the neuraxis at diagnosis have been identified as high-risk patients. The objective of our study was to determine tumor response, survival rates and toxicity with anew scheme of treatment with carboplatin, and etoposide and radiotherapy. Methods. All patients received chemotherapy with carboplatin and etoposide every 4 weeks for four courses, hyperfractionated radiotherapy, and another four courses of the above chemotherapy scheme. Tumor response was classified, and global and disease-free survival rates were calculated according to the actuarial survival method. Results. A total of 26 patients were included, with a median age of 6.9 years. Nineteen achieved complete response after the first four courses of chemotherapy, and two more had a complete response after radiotherapy. A total of seven children have died, three of whom did not respond to initial treatment. Global and disease-free survival rates were 69 percent and 64 percent, respectively, at 60 months of follow-up. There was no renal or auditory toxicity. Hematological toxicity was transitory and reversible. Conclusions. This scheme of treatment is effective and can be safely used for pediatric patients with hig-risk medulloblastomas. Toxicity was not significants, and survival is similar to other reports