title: Phase I study of temozolomide and lomustine in the treatment of high grade malignant glioma.
abstract: Systematic reviews and meta-analysis have demonstrated an improved prognosis by chemotherapy of malignant glioma patients. The effects of clinical research therefore have the aim to find more active drugs or new combination therapies. The combination of Temozolomide (TMZ) and nitrosoureas was evaluated preclinically with an evidence of therapeutic synergy. Based on these findings, we have carried out a phase I study with TMZ administered in low, prolonged doses of 75 mg/m2 per day, once a day for 21 days, escalated in cohorts of 3 patients, in combination with a fixed dose of Lomustine (CCNU) 100 mg/m2 orally on day 1. MTD was evident. The treatment was generally well tolerated. We did not observe bleeding or severe infections, as described for several combination chemotherapies with TMZ and other agents. In this study, for the first time in high grade malignant glioma, two orally administrated drugs were associated .TMZ 75 mg/m2 for 28 consecutive days and CCNU 100 mg/m2 on day 1 of every 6 weeks could be recommended as a safe treatment dosage. One of the ten patients evaluated for clinical response showed a partial response, while nine showed stability of disease, with a median duration of from 5 to 6 months.
authors.affiliation: Department of Medical Oncology, S. Maria delle Grazie Hospital, Pozzuoli, Italy. salvatore.tafuto@libero.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Tafuto
authors.forename: Paolo
authors.initials: P
authors.lastname: Muto
authors.forename: Anna
authors.initials: A
authors.lastname: Tortoriello
authors.forename: Agata
authors.initials: A
authors.lastname: Pisano
authors.forename: Pasquale
authors.initials: P
authors.lastname: Comella
authors.forename: Roberta
authors.initials: R
authors.lastname: Formato
authors.forename: Stefano
authors.initials: S
authors.lastname: Quattrin
authors.forename: Rosario Vincenzo
authors.initials: RV
authors.lastname: Iaffaioli
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D015331:Cohort Studies; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008130:Lomustine; D003606:Dacarbazine; D000077204:Temozolomide