A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease.
BACKGROUND
This study compared irinotecan plus cisplatin (IP) with etoposide plus cisplatin (EP) in small-cell lung cancer patients with extensive disease.


METHODS
Patients were randomly assigned to receive cisplatin 80 mg/m(2) and either irinotecan 65 mg/m(2), days 1 and 8 or etoposide 100 mg/m(2), days 1-3, every 3 weeks.


RESULTS
Baseline characteristics were balanced between patients receiving IP (N = 202) or EP (N = 203). Median overall survival was nonsignificantly superior for patients receiving IP versus EP, 10.2 versus 9.7 months [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.65-1.01, P = 0.06] and 1- and 2-year survival rates were 41.9% versus 38.9% and 16.3% versus 8.2%, respectively. Noninferiority of IP versus EP was established, upper bound of the 95% CI of HR 1.01 (prespecified margin IP/EP <1.25). Overall response (39.1% versus 46.6%) and time to tumor progression (5.4 versus 6.2 months) were not superior for IP. Grade 3/4 vomiting (10.9% versus 4.4%) and diarrhea (15.4% versus 0.5%) were more common in the IP versus EP arm; grade 3/4 neutropenia was more frequent in the EP (59.6%) versus IP arm (38.1%).


CONCLUSIONS
Our data demonstrate the noninferiority of IP versus EP for survival in primarily Western patients with SCLC-ED. A meta-analysis is required to finally assess the role of irinotecan in this setting.
Department of Pneumology, Third Faculty of Medicine, Faculty Hospital Bulovka and Postgraduate Medical Institute, Charles University, Prague, Czech Republic. Electronic address: zatloukp@fnb.cz.
P
P
Zatloukal
Department of Medical Oncology, Institut Català d'Oncologia, Barcelona, Spain.
F
F
Cardenal
Regional Lung Diseases Hospital, Otwock, Poland.
A
A
Szczesna
Department of Chemotherapy, Cancer Research Centre, Moscow, Russian Federation.
V
V
Gorbunova
N.N. Petrov Research Institute of Oncology of Federal Agency of High-tech Medical Treatment, St Petersburgh, Russian Federation.
V
V
Moiseyenko
Pfizer Inc., New York, NY, USA.
X
X
Zhang
Pfizer Inc., New York, NY, USA.
L
L
Cisar
Department of Medicine, Lung Cancer Unit, Institut Gustave Roussy, Villejuif, France.
J-C
JC
Soria
Department of Medical Oncology, Hospital Fundación Jiménez Diaz, Madrid, Spain.
M
M
Domine
Department of Internal Medicine, Thoracic Oncology, Clinic for Thoracic Diseases at the University of Heidelberg, Heidelberg, Germany.
M
M
Thomas
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007390:International Agencies; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin