Multicenter randomized open-label phase III study comparing efficacy, safety, and tolerability of conventional carboplatin plus etoposide versus dose-intensified carboplatin plus etoposide plus lenograstim in small-cell lung cancer in "extensive disease" stage.
BACKGROUND
The combination of carboplatin and etoposide (CE) is one of the most effective regimens in the treatment of small-cell lung cancer (SCLC). The aim of this study was to investigate whether dose-intensified CE with the supplementation of granulocyte-colony-stimulating factor (G-CSF) is more effective than conventional CE in terms of survival with acceptable toxicity.


METHODS
In a 2-arm multicentric prospective open label study, adult patients with SCLC in "extensive disease" stage were randomized either to conventional CE (carboplatin AUC 5 on day 1 IV and etoposide 140 mg/m IV on days 1-3, q28 days) or to dose-intensified therapy (carboplatin AUC 5 on day 1 IV and etoposide 190 mg/m days 1-3 IV with lenograstim 263 microg subcutaneously on days 4-13, q21 days). Primary end point was overall survival; secondary endpoints were toxicity, quality of life, and disease-free survival.


RESULTS
Seventy-nine patients were included. Thirty-seven received conventional CE and 42 received the dose-intensified regimen. Median survival in the conventional group and the dose-intensified group were 11.2 months [confidence interval (CI) 9.1-15.2] and 11.7 months (CI 8.8-14.7), respectively. Progression-free survival was 6.7 (CI 5.8-7.5) and 7.4 months (CI 6.2-9.0), respectively. There was no statistically significant difference between these groups. Grade 3/4 neutropenia occurred in 69.4% in the conventional arm versus 37.5% in the dose-intensified group (P = 0.009).


CONCLUSIONS
Dose-intense CE with GM-CSF support can be administered safely but does not prolong overall or progression-free survival compared with standard therapy.
Heigener
David Felix
DF
Department of Oncology, Krankenhaus Grosshansdorf, Grosshansdorf, Schleswig-Holstein, Germany.
Manegold
Christian
C
Jäger
Elke
E
Saal
Johannes-Georg
JG
Zuna
Ivan
I
Gatzemeier
Ulrich
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D000078224:Lenograstim; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins / Q000627:therapeutic use; D012449:Safety; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D000078224:Lenograstim; D016190:Carboplatin