title: A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.
abstract: A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.
authors.affiliation: Department of Neuro-Oncology, UTMD Anderson Cancer Center, Box 100, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Yung
authors.forename: R E
authors.initials: RE
authors.lastname: Albright
authors.forename: J
authors.initials: J
authors.lastname: Olson
authors.forename: R
authors.initials: R
authors.lastname: Fredericks
authors.forename: K
authors.initials: K
authors.lastname: Fink
authors.forename: M D
authors.initials: MD
authors.lastname: Prados
authors.forename: M
authors.initials: M
authors.lastname: Brada
authors.forename: A
authors.initials: A
authors.lastname: Spence
authors.forename: R J
authors.initials: RJ
authors.lastname: Hohl
authors.forename: W
authors.initials: W
authors.lastname: Shapiro
authors.forename: M
authors.initials: M
authors.lastname: Glantz
authors.forename: H
authors.initials: H
authors.lastname: Greenberg
authors.forename: R G
authors.initials: RG
authors.lastname: Selker
authors.forename: N A
authors.initials: NA
authors.lastname: Vick
authors.forename: R
authors.initials: R
authors.lastname: Rampling
authors.forename: H
authors.initials: H
authors.lastname: Friedman
authors.forename: P
authors.initials: P
authors.lastname: Phillips
authors.forename: J
authors.initials: J
authors.lastname: Bruner
authors.forename: N
authors.initials: N
authors.lastname: Yue
authors.forename: D
authors.initials: D
authors.lastname: Osoba
authors.forename: S
authors.initials: S
authors.lastname: Zaknoen
authors.forename: V A
authors.initials: VA
authors.lastname: Levin
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D018316:Gliosarcoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011344:Procarbazine / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D011788:Quality of Life; D012008:Recurrence; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D011344:Procarbazine; D003606:Dacarbazine; D000077204:Temozolomide