Ana Carolina Sepúlveda-Vildósola

Palonosetron Hydrochloride Is an Effective and Safe Option to Prevent Chemotherapy-induced Nausea and Vomiting in Children

BACKGROUND Emesis and nausea are common adverse effects of chemotherapy. Consequences include dehydration, acute renal failure, esophageal rupture, electrolyte imbalance and undernutrition, among others. First-generation 5-HT3 antagonists significantly reduce these symptoms but are expensive and require administration every 8-12h. Palonosetron, a second generation 5-HT3 antagonist has proven better results in adult populations. Other benefits include a one-dose administration with effect for up to 7 days and a lower treatment cost. No clinical studies have evaluated the safety and efficacy of palonosetron in children. METHODS Prior to every course, patients were randomized to receive palonosetron or ondansetron. Patients or guardians recorded the number of emetic events and the intensity of nausea over a 7-day period. They also reported any possible adverse effects. Statistical analysis included chi(2) test, relative risk, and Students t test. RESULTS Fifty courses were analyzed for each group. There was a significant reduction in emesis on the first 3 days and in the intensity of nausea in the first four days in the palonosetron group. There was an increased risk of presenting emesis and nausea in the acute phase when treated with ondansetron. No adverse effects were reported. The cost of treatment was also reduced when using palonosetron. CONCLUSIONS Palonosetron is a safe and effective antiemetic treatment in children, as well as being cost effective.

Phase II Study of Metronomic Chemotherapy with Thalidomide, Carboplatin-Vincristine-Fluvastatin in the Treatment of Brain Stem Tumors in Children

BACKGROUND Brain stem tumors (BST) constitute 20% of all intracranial tumors. Survival for these patients has been very poor worldwide. Four different treatment schemes have been evaluated at our institution, with only a discrete increment in survival when treated with carboplatin-vincristine and fluvastatin (CVF). Low-dose, continuous antiangiogenic treatment has been recently introduced in the treatment of cancer. Our objective was to determine tumor response to metronomic chemotherapy combined with an antiangiogenic drug and fluvastatin and to calculate the survival of pediatric patients with brain stem tumors. METHODS This was a phase II study. A magnetic resonance (MRI) study was made at inclusion and after the fourth course. Routine laboratory analyses were performed prior to each treatment scheme. Patients received four courses of chemotherapy every 28 days consisting of thalidomide alternating with fluvastatin every 14 days and combined with carboplatin and vincristine every 14 days followed by radiotherapy (56 cGy) and four more courses of the same chemotherapy. Toxicity was evaluated according to Miller criteria. RESULTS Nine recently diagnosed BST patients were included. Five patients had low-grade astrocytomas, three patients had glioblastoma multiforme, and one patient presented high-grade astrocytoma. There was a significant reduction in tumor volume and a significant increase in survival at 24 months. Two patients died. Toxicity included carboplatin allergy in one patient, grades 1 and 3 neutropenia in two patients, and grade 4 thrombocytopenia in two patients. CONCLUSIONS Metronomic treatment with carboplatin and vincristine associated with fluvastatin and thalidomide significantly increased survival of pediatric brain stem tumor patients. Tumor volume showed a significant reduction. Quality of life was also increased. Sample size must be increased in order to make final conclusions.

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. 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 Ewings 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.

Preirradiation Ifosfamide, Carboplatin, and Etoposide for the Treatment of Anaplastic Astrocytomas and Glioblastoma Multiforme: A Phase II Study

BACKGROUND Central nervous system (CNS) tumors are the second most common pediatric tumors. Astrocytomas represent 35% of all CNS tumors in children. Traditional treatment of anaplastic astrocytoma (AA) and glioblastoma multiforme (GM) consisting of surgery-radiotherapy-chemotherapy with nitrosoureas has resulted in a survival rate of 26% at 1 year. Neoadjuvant chemotherapy has proven good results in the treatment of other solid tumors. Chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) permits synergism among the different drugs and sensitizes the tumor to radiotherapy. Our objective was to evaluate the efficacy, security, and survival rate of postoperative chemotherapy with ICE in pediatric patients with AA or GM. METHODS Phase II study. We evaluated 11 children with AA or GM who had received no prior treatment. A magnetic resonance image (MRI) study of the tumor was made after surgery to evaluate residual tumor and routine laboratory analysis. Chemotherapy with carboplatin, ifosfamide and etoposide was given every 3 weeks for four courses. MRI studies were repeated after the second and last courses and laboratory analyses were carried out before each course to evaluate toxicity. Each patient then received hyperfractionated radiotherapy and a final MRI was done at the end of the treatment. RESULTS Sixty percent of the patients had partial response, 30% complete response after two courses, and 60% of CR after four courses. Supratentorial and infratentorial tumors had a good response to chemotherapy. Brainstem tumors had an initial response after two courses and then increased in size. AA was the tumor with the greatest reduction of residual tumor after treatment. Overall and free survival at 53 months was 70%. To date, three patients have died secondary to tumoral progression. There have been no relapses in the seven patients with a CR. CONCLUSIONS Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity. Brainstem responded poorly to treatment.