Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group.
OBJECTIVE
This phase III study compared overall survival in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) when treated with single-agent gemcitabine versus gemcitabine/carboplatin. Secondary objectives were to compare response, time to progression, toxicity, and quality of life.


METHODS
Chemotherapy-naive patients received either gemcitabine alone (1,250 mg/m2 on days 1 and 8; gemcitabine arm) or with carboplatin (area under the curve 5 on day 1; GC arm) every 21 days.


RESULTS
Demographics and disease characteristics of 334 randomly assigned patients were comparable on both arms. An intent-to-treat analysis showed significantly better overall survival (log-rank P = .0205) and 2-year survival (15% v 5%; P = .009) favoring the GC arm. Per Cox multivariate analysis, only two covariates, treatment arm (GC v G) and baseline performance status (0 or 1 v 2), independently influenced survival. Per-protocol analyses showed significantly longer median time to progression (5.7 v 3.9 months; P = .0001) and significantly higher objective response rate (29.6 v 11.3%; P < .0001) in the GC arm. Grade 3 to 4 leucopenia and thrombocytopenia were significantly more pronounced in the GC arm (P for both variables < .001) but importantly without associated increases in fever, infection, bleeding, or hospitalizations. There was no discernible difference in global quality-of-life patterns between treatment arms.


CONCLUSIONS
In advanced NSCLC, gemcitabine/carboplatin therapy resulted in significant survival benefit compared with single-agent gemcitabine without undue increase in toxicity.
Sederholm
Christer
C
Department of Pulmonary Medicine, Oncologic Center, University Hospital, Linköping, Sweden. christer.sederholm@lio.se
Hillerdal
Gunnar
G
Lamberg
Kristina
K
Kölbeck
Karl
K
Dufmats
Monika
M
Westberg
Ronny
R
Gawande
Sulochana R
SR
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011788:Quality of Life; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013548:Sweden / Q000453:epidemiology; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine