Randomized phase II trial of gemcitabine plus weekly versus three-weekly paclitaxel in previously untreated advanced non-small-cell lung cancer

• Published in: Annals of oncology Vol. 18; no. 1; pp. 110 - 115
• Main Authors: Belani, C.P., Dakhil, S., Waterhouse, D.M., Desch, C.E., Rooney, D.K., Clark, R.H., Monberg, M.J., Ye, Z., Obasaju, C.K.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2007; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - secondary; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Large Cell - drug therapy; Carcinoma, Large Cell - secondary; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - secondary; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Female; gemcitabine; Humans; Infusions, Intravenous; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; non-platinum doublets; non-small-cell lung cancer; paclitaxel; Paclitaxel - administration & dosage; Pharmacology. Drug treatments; Pneumology; Prognosis; Survival Rate; Treatment Outcome; Tumors of the respiratory system and mediastinum; paclitaxel; gemcitabine; non-platinum doublets; non-small-cell lung cancer; Antineoplastic agent; Human; Lung disease; Gemcitabine; Respiratory disease; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Randomization; Antimetabolic; Platinum; Taxane derivatives; Phase II trial; Paclitaxel; Bronchus disease; Pyrimidine derivatives; Clinical trial; Advanced stage; Fluorine Organic compounds; Antimitotic; Pyrimidine nucleoside; Comparative study
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdl344

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.