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.
Zatloukal
P
P
Department of Pneumology, Third Faculty of Medicine, Faculty Hospital Bulovka and Postgraduate Medical Institute, Charles University, Prague, Czech Republic. Electronic address: zatloukp@fnb.cz.
Cardenal
F
F
Department of Medical Oncology, Institut Català d'Oncologia, Barcelona, Spain.
Szczesna
A
A
Regional Lung Diseases Hospital, Otwock, Poland.
Gorbunova
V
V
Department of Chemotherapy, Cancer Research Centre, Moscow, Russian Federation.
Moiseyenko
V
V
N.N. Petrov Research Institute of Oncology of Federal Agency of High-tech Medical Treatment, St Petersburgh, Russian Federation.
Zhang
X
X
Pfizer Inc., New York, NY, USA.
Cisar
L
L
Pfizer Inc., New York, NY, USA.
Soria
J-C
JC
Department of Medicine, Lung Cancer Unit, Institut Gustave Roussy, Villejuif, France.
Domine
M
M
Department of Medical Oncology, Hospital Fundación Jiménez Diaz, Madrid, Spain.
Thomas
M
M
Department of Internal Medicine, Thoracic Oncology, Clinic for Thoracic Diseases at the University of Heidelberg, Heidelberg, Germany.
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