Adding Gemcitabine to Paclitaxel/Carboplatin Combination Increases Survival in Advanced Non–Small-Cell Lung Cancer: Results of a Phase II-III Study

• Published in: Journal of clinical oncology Vol. 24; no. 4; pp. 681 - 687
• Main Authors: Paccagnella, Adriano, Oniga, Francesco, Bearz, Alessandra, Favaretto, Adolfo, Clerici, Maurizia, Barbieri, Fausto, Riccardi, Alberto, Chella, Antonio, Tirelli, Umberto, Ceresoli, Giovanni, Tumolo, Salvatore, Ridolfi, Ruggero, Biason, Rita, Nicoletto, Maria Ornella, Belloni, Paolo, Veglia, Fabrizio, Ghi, Maria Grazia
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 01.02.2006
• Subjects: Adult; Aged; Aged, 80 and over; Anemia - chemically induced; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Middle Aged; Multivariate Analysis; Neutropenia - chemically induced; Paclitaxel - administration & dosage; Prognosis; Risk Factors; Survival Rate; Thrombocytopenia - chemically induced; Treatment Outcome
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.03.2722

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. 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/m(2) and carboplatin area under the concentration-time curve 6 day 1, and gemcitabine 1,000 mg/m2 days 1 and 8 every 21 days). A total of 324 patients were randomly assigned to the two arms. The RR for PC arm and PCG arm were 20.2% and 43.6% [corrected] (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. The PCG regimen offers a significant survival advantage over PC in advanced NSCLC, making PCG a treatment option for advanced NSCLC patients.