title: Feasibility study of 21-day-on/7-day-off temozolomide in children with brain tumors.
abstract: Temozolomide (TMZ) is an oral alkylating agent with proven antitumoral activity in preclinical and clinical studies in adults with high-grade glioma (HGG). However, only limited efficacy has been reported in children with HGG using the 5-day schedule. This study investigated the safety of administering TMZ to children and adolescents with brain tumors over an extended period. Extended schedules have been proven to overcome chemoresistance without any major toxicity. The toxicity of TMZ, administered at 70 mg/m(2)/day orally for 21 consecutive days every 28 days, was assessed in children with brain tumors. A total of 156 courses of TMZ were given to 17 patients (median age 12.5 years, range 1-17 years), who were recruited into the study. Eleven patients had progressive or relapsing disease, and six patients were newly diagnosed. In this cohort no cases of toxic death or nonhematological toxicity were reported. In comparison with the 5-day schedule, thrombocytopenia and neutropenia were noted to be less frequent. Grades 3 and 4 lymphopenia occurred in 10.8 and 22.4% of courses, respectively; among the lymphopenic patients there was one case of disseminated zoster (meningoencephalitis and cutaneous involvement), one case of rotavirus gastroenteritis, and two cases of herpetic stomatitis reported. The objective response rate was 11.8%. Overall, 82.3% of patients showed stable disease. The prolonged TMZ schedule appeared to be well tolerated, with few cases of neutropenia or thrombocytopenia recorded. Nevertheless, prolonged exposure to TMZ was associated with lymphopenia and may lead to a higher rate of viral infections.
authors.affiliation: Department of Pediatric Oncology, A. Gemelli Hospital, Catholic University of Rome, Largo A Gemelli 1, 00168 Rome, Italy. vita.ridola@rm.unicatt.it
authors.forename: Vita
authors.initials: V
authors.lastname: Ridola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Barone
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lazzareschi
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruggiero
authors.forename: Daniela
authors.initials: D
authors.lastname: Rizzo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Riccardi
mesh_terms: D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
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