Effects of concurrent topotecan and radiation on 6-month progression-free survival in the primary treatment of glioblastoma multiforme.
OBJECTIVE
To report a prospective, randomized, Phase II trial of radiotherapy with and without topotecan for the treatment of glioblastoma.


METHODS
Inclusion criteria were histology of glioblastoma, age <60 years, and Eastern Cooperative Oncology Group status 0-2. Patients were stratified according to recursive partitioning analysis class, center, and enzyme-inducing antiepileptic medication. Magnetic resonance imaging scans, neurologic examinations, and quality of life assessments were done every 3 months. The primary endpoint was the progression-free survival rate at 6 months (6-m-PFS). This trial was designed as an exploratory, randomized, Phase II trial with an accrual of 140 patients to detect a difference of 15-20% in 6-m-PFS. An interim analysis was scheduled after 60 patients. Median follow-up was 14 months (range, 1-50 months).


RESULTS
The 6-m-PFS was 56% and 40% for patients with and without topotecan, respectively. This benefit disappeared within 2 months. Mean (range) progression-free survival time was 8 (5-10.9) months and 6.7 (4-9.5) months for patients with and without topotecan, respectively. The corresponding 2-year-overall survival rates were 28% vs. 22% (nonsignificant difference), and mean (range) survival time was 20.7 (13.9-27.5) months vs. 18.9 (13.5-24.4) months (nonsignificant difference).


CONCLUSIONS
A slight but measurable increase of 16% was detected in 6-m-PFS for patients receiving topotecan with radiation as compared with patients having radiotherapy alone. These data might support further investigations into topotecan for the treatment of glioblastoma.
Grabenbauer
Gerhard G
GG
Department of Radiation Oncology, University Hospitals of Erlangen, Erlangen, Germany. gg@diacura.de
Gerber
Klaus-Dieter
KD
Ganslandt
Oliver
O
Richter
Andrea
A
Klautke
Gunther
G
Birkmann
Josef
J
Meyer
Martin
M
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D011879:Radiotherapy Dosage; D019772:Topotecan / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
D000970:Antineoplastic Agents; D019772:Topotecan