Annals of Oncology Advance Access originally published online on October 16, 2006
Annals of Oncology 2007 18(1):110-115; doi:10.1093/annonc/mdl344
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© 2006 European Society for Medical Oncology
lung cancer |
Randomized phase II trial of gemcitabine plus weekly versus three-weekly paclitaxel in previously untreated advanced non-small-cell lung cancer
1 University of Pittsburgh Cancer Institute, Pittsburgh, PA
2 Cancer Center of Kansas, P.A., Wichita, KS
3 The Jewish Hospital-Kenwood, Cincinnati, OH
4 Hematology and Oncology of Virginia, Richmond, VA
5 Hematology/Oncology, Inc., Canton, OH
6 Hematology/Oncology Associates, Jackson, MI
7 Lilly Research Laboratories, Indianapolis, IN, USA
* Correspondence to: C. P. Belani, Professor of Medicine, Co-Director, Lung and Thoracic Center Program, University of Pittsburgh Cancer Institute, 5150 Center Avenue, Pittsburgh, PA 15213, USA. Tel: +1 412-648-6619; Fax: +1 412-648-6579; E-mail: belanicp{at}upmc.edu
Introduction: Gemcitabine and paclitaxel (Taxol) each provides an efficacious non-platinum option for the treatment of advanced non-small-cell lung cancer (NSCLC), but the optimal dosage and schedule of the two agents used in combination are not well defined.
Methods: Previously untreated patients with advanced NSCLC were randomized to receive gemcitabine–paclitaxel on a traditional three-weekly schedule (Arm A) or a novel weekly schedule (Arm B) as follows—Arm A (three-weekly): gemcitabine 1000 mg/m2 infused >30 min on days 1 and 8 and paclitaxel 200 mg/m2 infused >3 h on day 1 of a 21-day cycle or Arm B (weekly): gemcitabine 1000 mg/m2 infused >30 min and paclitaxel 100 mg/m2 infused >1 h, both administered on days 1 and 8 of a 21-day cycle.
Results: One hundred patients received at least one dose of treatment. The weekly schedule, Arm B, was more efficacious and less hematologically toxic than Arm A. Confirmed complete and partial response rates were 28.2% and 26.8%, respectively. Median survival was 10.3 months on Arm B and 7.9 months on Arm A (log-rank P = 0.10); 1- and 2-year survival rates also favor Arm B: 42.0% versus 34.0% and 18.0% versus 6.0%. Progression-free survival was 5.8 versus 4.8 months, again favoring Arm B (log-rank P = 0.06). There was a two-fold lower frequency of grade 3/4 hematologic events with Arm B as follows: neutropenia (16% versus 30%), thrombocytopenia (4% versus 8%), and anemia (2% versus 6%). One patient (2%) in each treatment group developed febrile neutropenia.
Conclusion: In this trial, both schedules were efficacious and tolerable, although the weekly schedule resulted in improved survival and lower hematologic toxicity compared with a three-weekly schedule. The weekly schedule of gemcitabine–paclitaxel indicates an improved therapeutic index.
Key words: gemcitabine, non-platinum doublets, non-small-cell lung cancer, paclitaxel