Karl Kölbeck

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

PURPOSE 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. PATIENTS AND 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. CONCLUSION In advanced NSCLC, gemcitabine/carboplatin therapy resulted in significant survival benefit compared with single-agent gemcitabine without undue increase in toxicity.

Pemetrexed and Gemcitabine Versus Carboplatin and Gemcitabine in Non-Small Cell Lung Cancer: A Randomized Noninferiority Phase II Study in One Center

BACKGROUND The standard treatment for non-small cell lung cancer (NSCLC) stages IIIb and IV is a platinum compound combined with a third-generation cytotoxic agent. We decided to conduct a phase II study to assess whether the platinum compound could be replaced with pemetrexed with similar results and without an increase in side effects. METHODS Consecutive eligible patients were randomized to either the standard arm of gemcitabine plus carboplatin (GC) or the experimental arm of gemcitabine plus pemetrexed (GP). RESULTS Fifty evaluable patients were enrolled in the GC arm, and 44 received GP. There were 10 partial responses in the GC arm and 16 in the GP arm. With GC, mean survival was 9 months compared with 15 months with GP. The side effects were similar in both groups. CONCLUSION Pemetrexed can replace platinum compounds in the first-line treatment of stage IIIb and IV NSCLC without increasing the side effects. A trend toward better survival was observed in the patients receiving pemetrexed instead of a platinum compound, and this should be studied further.

Pemetrexed plus gemcitabine versus gemcitabine plus carboplatin in patients with advanced nonoperable NSCLC: A randomized phase II study.

e18039 Background: The standard first-line treatment of inoperable Non-Small Cell Lung Cancer (NSCLC) is a combination of two drugs, one of which should be a platinum drug. We investigated a combination of two modern drugs without platinum in a single institute randomized study. Methods: Consecutive patients with NSCLC, stage III B inoperable or IV, PS 0-2, September 2006-October 2009, were randomized to pemetrexed, 500 mg/m2 + gemcitabine, 1,500 mg/m2 every second week (PG arm), or gemcitabine, 1,250 mg/m2 day 1 and 8 and carboplatin 5 AUC day 1 every 3 weeks (GC arm). Unless progression of disease, toxicity, or withdrawal of consent, 6 courses were given in the PG arm and 4 courses in the AG arm. Results: Forty-seven patients were randomized to the PG and 50 to the GC arm. Three patients were excluded, leaving 46 in the PG and 48 in the GC arm. In the PG arm, 22% stopped treatment due to side effects, and 4% in the GC arm. The only lethal side effect was seen in the GC arm. In the PG arm, 20% stopped tr...