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Docetaxel/gemcitabine or cisplatin/gemcitabine followed by docetaxel in the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC): results of a multicentre randomized phase II trial

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Abstract

Background

Most patients (pts) with metastatic non-small cell lung cancer (NSCLC) receive either single agents or chemotherapy doublets. Recent studies have demonstrated that triple-agent therapies may improve the response rate, but are associated with significant toxicity, and frequently do not prolong survival. A sequential triple-agent schedule may combine acceptable tolerability and good efficacy. We therefore conducted a multicentre, prospectively randomized study that evaluates a sequential three-drug schedule and a platinum-free doublet regimen.

Patients and methods

The pts with union international contre le cancer (UICC) stage IV NSCLC were randomized to one of two schedules: in arm Doc-Gem, they received gemcitabine (900 mg/m2, 30 min infusion) on days 1 and 8, and docetaxel (75 mg/m2, 1 h infusion) on day 1, repeated every 3 weeks up to six cycles. In arm Cis-Gem→Doc, gemcitabine (900 mg/m2, days 1 and 8) and cisplatin (70 mg/m2, 1 h infusion, day 1) were given for three cycles, followed by three cycles of docetaxel (100 mg/m2, day 1, repeated every 3 weeks).

Results

One hundred and thirteen pts were randomized to arms Doc-Gem (55 pts) and Cis-Gem→Doc (58 pts). With Doc-Gem, 20.4% of pts responded to the treatment whereas 31.0% responded in arm Cis-Gem→Doc (overall response, intent-to-treat, difference not significant). The median time to progression was 3.6 months in arm Doc-Gem [95% confidence interval (CI) 1.4, 5.9] and 5.2 months in arm Cis-Gem→Doc (95% CI 3.1, 7.3). The median survival was 8.7 months with treatment Doc-Gem (95% CI 5.7, 11.6) and 9.4 months with treatment Cis-Gem→Doc (95% CI 7.8, 11.0). The 1-year survival rates were 34 and 35%, respectively. Mild to moderate leukopenia was frequently seen with both schedules. Other common adverse events (AE) were nausea/vomiting, thrombocytopenia, anaemia, diarrhoea, and infections. No significant differences in AEs were observed between the schedules except for nausea/vomiting, which occurred more frequently with Cis-Gem→Doc.

Conclusion

The sequential therapy comprising cisplatin, gemcitabine, and docetaxel demonstrated promising tumour control whereas the platinum-free combination (docetaxel/gemcitabine) was very well tolerated. However, the schedules resulted in comparable survival to recent large trials in pts with advanced NSCLC. The present results do not justify further phase III investigation.

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Acknowledgments

This trial was supported by Sanofi-Aventis Deutschland GmbH, part of the Sanofi-Aventis Group. Dr. Binder has received lecture honoraria from Sanofi-Aventis.

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Authors and Affiliations

  1. Medizinische Klinik m. S. Infektiologie und Pneumologie, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    D. Binder, C. Schäper, B. Temmesfeld-Wollbrück & N. Suttorp

  2. III. Medizinische Klinik, Carl-Thiem-Klinikum, Cottbus, Germany

    H. Schweisfurth

  3. Medizinische Klinik m. S. Kardiologie Pneumologie, Gemeinschaftskrankenhaus Havelhöhe, Berlin, Germany

    C. Grah

  4. Institut für Medizinische Biometrie, Charité—Universitätsmedizin Berlin, Berlin, Germany

    G. Siebert

  5. Hämatologie und internistische Onkologie, Klinik Wartenberg, Wartenberg, Germany

    T. Beinert

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  1. D. Binder
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  2. H. Schweisfurth
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Correspondence to D. Binder.

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Binder, D., Schweisfurth, H., Grah, C. et al. Docetaxel/gemcitabine or cisplatin/gemcitabine followed by docetaxel in the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC): results of a multicentre randomized phase II trial. Cancer Chemother Pharmacol 60, 143–150 (2007). https://doi.org/10.1007/s00280-006-0358-7

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  • DOI: https://doi.org/10.1007/s00280-006-0358-7

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