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Single agents in the second-line treatment of non-small cell lung cancer
1Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, PA 15213, USA.
Abstract:
The options available to patients with advanced non-small cell lung cancer (NSCLC) resistant or refractory to first-line chemotherapy are very limited. The older-generation drugs (etoposide, vindesine, epirubicin, and cisplatin) that are active against previously untreated NSCLC do not achieve a response rate greater than 10% when used in the second-line setting. The newer-generation agents with activity in previously untreated NSCLC include carboplatin, paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan. Although NSCLC remains relatively resistant to chemotherapy, the fact that second-line chemotherapy is being considered is tribute to the progress being made with first-line therapy. The taxanes have clearly become the agents of the 1990s. The activity of paclitaxel in the second-line setting is not well-defined, and the response rates have ranged from 0% to 3 31% using various schedules. However, docetaxel achieved response rates of 15% to 22% in five phase II trials, with a clinically meaningful survival rate of 25% at 1 year in one of the studies. Randomized trials of docetaxel versus best supportive care and of docetaxel versus vinorelbine or ifosfamide are in progress. The efficacy of vinorelbine and irinotecan in the second-line setting have been dismal. Gemcitabine demonstrated a response rate of 25% in a recently reported trial and needs further investigation. Further progress may come from a wider investigation of novel agents and their combination with biological and other selective therapies.
Insights
Second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) offers limited options. Docetaxel shows promise with response rates up to 22%, while gemcitabine requires further study for NSCLC treatment.
Area of Science:
- Oncology
- Medical Oncology
- Pharmacology
Background:
- Patients with advanced non-small cell lung cancer (NSCLC) resistant to first-line chemotherapy have limited treatment choices.
- Older chemotherapy agents show less than 10% response rates in the second-line setting for NSCLC.
- Newer agents like taxanes, gemcitabine, and irinotecan are being investigated for advanced NSCLC.
Purpose of the Study:
- To review the efficacy of second-line chemotherapy agents in advanced non-small cell lung cancer (NSCLC).
- To evaluate the role of newer-generation drugs, particularly taxanes, in the treatment of refractory NSCLC.
- To identify promising agents for further investigation in advanced NSCLC.
Main Methods:
- Review of phase II trials and reported response rates for various chemotherapy agents in second-line NSCLC treatment.
- Analysis of efficacy data for paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan.
- Consideration of ongoing randomized trials comparing docetaxel with other treatments or best supportive care.
Main Results:
- Docetaxel demonstrated response rates of 15-22% in phase II trials for advanced NSCLC, with one study showing a 25% 1-year survival rate.
- Paclitaxel's efficacy in the second-line setting for NSCLC is variable, with reported response rates from 0% to 31%.
- Gemcitabine showed a 25% response rate in a recent trial, warranting further investigation; vinorelbine and irinotecan showed limited efficacy.
Conclusions:
- Docetaxel is a promising agent for second-line treatment of advanced non-small cell lung cancer (NSCLC), with ongoing trials to confirm its benefit.
- Gemcitabine requires further investigation for its potential role in advanced NSCLC treatment.
- Future progress in treating advanced NSCLC may involve novel agents and combination therapies, including biological treatments.