Randomized, multicenter, open-label phase II study of gemcitabine plus single-dose versus split-dose carboplatin in the treatment of patients with advanced-stage non-small-cell lung cancer.
BACKGROUND
Gemcitabine/carboplatin is a convenient and effective treatment for advanced-stage non-small-cell lung cancer (NSCLC), but modification of the schedule to diminish thrombocytopenia is worthwhile.


METHODS
One hundred fifty-eight chemotherapy-naive patients with stage IIIB/IV NSCLC were randomized from 15 centers in Germany to receive gemcitabine 1250 mg/m(2) on days 1 and 8 plus carboplatin area under the curve 5 on day 1 (arm A) or carboplatin area under the curve 2.5 on days 1 and 8 (arm B), every 21 days for 4 cycles.


RESULTS
The 2 arms (A vs. B) were well balanced with regard to patient baseline characteristics: stage IV 72.5% versus 69%, median Eastern Cooperative Oncology Group performance status 1 versus 1. The incidence of grade 3/4 hematologic toxicity was as follows (percentage of patients in arm A vs. B): leukopenia 37.5% versus 27% (P = 0.075), granulocytopenia 36% versus 36%, and thrombocytopenia 51% versus 35% (P = 0.017). Nonhematologic toxicity was modest and comparable with both schedules. The overall response rate was 46% versus 36% (P = 0.12), and 24% versus 42% had stable disease. Median progression-free survival (5.8 months vs. 6.1 months) and overall survival (11.7 months vs. 10.7 months) were not significantly different between arms A and B.


CONCLUSIONS
Splitting the dose of carboplatin between days 1 and 8 on the same days as gemcitabine results in a significantly decreased incidence of severe thrombocytopenia, without compromising the activity of the combination.
Schuette
Wolfgang
W
City Hospital Martha-Maria Halle Doelau, 2nd Medical Department, Roentgenstrasse 1, D-06120 Halle, Germany. schuette-wolfgang@web.de
Blankenburg
Thomas
T
Schneider
Claus-Peter
CP
von Weikersthal
Ludwig Fischer
LF
Guetz
Sylvia
S
Laier-Groeneveld
Gerhard
G
Virchow
Johann Christian
JC
Chemaissani
Assnad
A
Reck
Martin
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine