Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group.
OBJECTIVE
Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation.


METHODS
In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain.


RESULTS
One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087).


CONCLUSIONS
Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.
Postmus
P E
PE
Departments of Pulmonary Diseases and Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, the Netherlands.
Haaxma-Reiche
H
H
Smit
E F
EF
Groen
H J
HJ
Karnicka
H
H
Lewinski
T
T
van Meerbeeck
J
J
Clerico
M
M
Gregor
A
A
Curran
D
D
Sahmoud
T
T
Kirkpatrick
A
A
Giaccone
G
G
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D013713:Teniposide / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D013713:Teniposide