Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial.
BACKGROUND
This phase III study compared efficacy and safety of topotecan-cisplatin (TP) versus topotecan-etoposide (TE) versus cisplatin-etoposide (PE) in chemo-naïve extensive disease small-cell lung cancer patients.


METHODS
Seven hundred and ninety-five previously untreated patients were randomly assigned to TP (topotecan 1mg/m IV, d1-5; cisplatin 75 mg/m IV, d5; n = 358), PE (cisplatin 75 mg/m IV, d1; etoposide 100 mg/m IV, d1-3; n = 345) or TE (topotecan 1mg/m IV, d1-5; etoposide 80 mg/m IV, d3-5; n = 92). Primary endpoint was superiority of TP compared with PE, with the possibility to switch to a noninferiority test.


RESULTS
The TE arm was closed after recommendations by the Independent Data Safety Monitoring Board. Median survival was similar and met the predefined endpoint of noninferiority of TP to PE (44.9 versus 40.9 weeks; p = 0.40). One-year survival rate showed 39.7% for TP versus 36.1% for PE (p = 0.29). Median time to progression was significantly longer with TP (27.4 versus 24.3 weeks, p = 0.01). Overall response rates were significantly higher for TP (55.5% versus 45.5%, p = 0.01).Hematologic toxicity was slightly higher for TP regarding G 3/4 neutropenia (35.7/35.8%), G 3/4 thrombocytopenia (18.7/4.8%), G 3/4 anemia (11.6/6.7%), febrile neutropenia (2.0/2.7%), sepsis (1.7/1.2%), and toxicity-related deaths (5.2/2.7%).


CONCLUSIONS
TP is noninferior to PE in overall survival and superior in time to progression and overall response rates. Because of slightly worse toxicity profile TP is not a first-line standard treatment for patients with extensive disease small-cell lung cancer.
Department of Pneumology, Rangauklinik Ansbach, Ansbach, Germany.
Thomas H
TH
Fink
Rudolf M
RM
Huber
David F
DF
Heigener
Corrina
C
Eschbach
Cornelius
C
Waller
Ernst U
EU
Steinhauer
Johann C
JC
Virchow
Frank
F
Eberhardt
Hans
H
Schweisfurth
Michael
M
Schroeder
Thomas
T
Ittel
Simone
S
Hummler
Norbert
N
Banik
Thomas
T
Bogenrieder
Thomas
T
Acker
Martin
M
Wolf
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D019772:Topotecan / Q000008:administration & dosage
D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin