A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse.
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.
Yung
W K
WK
Department of Neuro-Oncology, UTMD Anderson Cancer Center, Box 100, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA.
Albright
R E
RE
Olson
J
J
Fredericks
R
R
Fink
K
K
Prados
M D
MD
Brada
M
M
Spence
A
A
Hohl
R J
RJ
Shapiro
W
W
Glantz
M
M
Greenberg
H
H
Selker
R G
RG
Vick
N A
NA
Rampling
R
R
Friedman
H
H
Phillips
P
P
Bruner
J
J
Yue
N
N
Osoba
D
D
Zaknoen
S
S
Levin
V A
VA
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
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D011344:Procarbazine; D003606:Dacarbazine; D000077204:Temozolomide