Adding gemcitabine to paclitaxel/carboplatin combination increases survival in advanced non-small-cell lung cancer: results of a phase II-III study

Purpose
Paclitaxel/carboplatin (PC) is one of the reference combinations in the treatment of non–small-cell
lung cancer (NSCLC). No triplet novel agent combination has until now shown superiority over a
two-drug combination for advanced NSCLC. We therefore conducted a clinical trial to test if
paclitaxel/carboplatin/gemcitabine (PCG) increases overall survival (OS) and response rate (RR)
over PC.
Methods
Stage IIIB patients not suitable for radical radiation treatment and stage IV chemotherapy-naive
patients with measurable disease and performance status of 0 to 2 were randomly assigned to PC
arm (paclitaxel 200 mg/m2 and carboplatin area under the concentration-time curve 6 day 1/q21
days) or the PCG arm (paclitaxel 200 mg/m2 and carboplatin area under the concentration-time
curve 6 day 1, and gemcitabine 1,000 mg/m2 days 1 and 8 every 21 days).
Results
A total of 324 patients were randomly assigned to the two arms. The RR for PC arm and PCG arm
were 20.2% and 46% (P .0001). The median time to the progression was 5.1 months in the PC
group and 7.6 months in the PCG group (P .012; hazard ratio [HR] 1.34; 95% CI: 1.06 to 1.72).
Median OS was 8.3 months and 10.8 months (P .032; HR 1.309; 95% CI: 1.03 to 1.67) in favor
of the PCG arm. One-year survival was 34% (PC arm) and 45% (PCG arm; P .032). Only
hematologic toxicity (neutropenia, thrombocytopenia, and anemia) was significantly increased in
the PCG arm and the experimental arm required more platelet and red blood cell transfusions, and
more granulocyte colony-stimulating factor usage. No toxic/early deaths were observed.
Conclusion
The PCG regimen offers a significant survival advantage over PC in advanced NSCLC, making PCG
a treatment option for advanced NSCLC patients.