The combination of docetaxel(Drug information on docetaxel) (Taxotere) and gemcitabine(Drug information on gemcitabine) (Gemzar) is active as first-line therapy for advanced, metastatic non-small-cell lung cancer and appears to be generally well tolerated, according to the results of a phase II study published in a recent issue of Cancer (89:516-522, 2000).
Of 34 patients, 15 (44%) had a partial response to treatment and 2 (6%) had a complete response, for an overall response rate of 50%. The median overall survival was 13 months, and the actual 1-year survival was 55.8%. An additional 10 patients (29%) achieved stable disease for a median of 6 months. Myelosuppression was the most common adverse reaction, but was usually not severe.
"We have not yet identified the optimal regimen for use as standard therapy in patients with advanced non-small-cell lung cancer, and there is a strong need for an alternative to conventional cisplatin(Drug information on cisplatin) [Platinol]-based chemotherapy," said Michael Hejna, MD, department of internal medicine, division of oncology, University Hospital of Vienna, Austria, and the study’s principal investigator. "Our finding that the combination of docetaxel and gemcitabine provides a good overall response rate with a particularly impressive survival rate given our patients’ poor health status is very encouraging."
Patient Characteristics and Dosing Schedule
Participants included 34 patients with advanced, measurable non-small-cell lung cancer who had not undergone prior chemotherapy and who had a life expectancy of at least 3 months. Three patients had stage IIIB disease, and 31 patients had stage IV disease; 24 (71%) had a World Health Organization performance status of 1 or 2, and 21(62%) had involvement of more than two organs. The median age of study participants was 61 years, with 16 patients (47%) over the age of 65 years.
"The rationale for combining these two drugs included their distinct mechanisms of action with different intracellular targets, high levels of single-agent activity in non-small-cell lung cancer, and recently published data in various tumor types, suggesting potential drug synergism between the taxanes and gemcitabine," said the study authors.
All patients received docetaxel at 80 mg/m2 administered intravenously over 90 minutes on day 1 and gemcitabine at 1,000 mg/m2 administered on days 1 and 10. Granulocyte colony-stimulating factor (G-CSF [Neupogen]), 5 µg/kg, was administered subcutaneously once a day on days 2 through 8. Treatment cycles were repeated every 3 weeks for a maximum of six cycles. A total of 163 cycles of treatment were administered throughout the investigation.
Study Results
The median duration of response to treatment was 6.5 months, and the median time to disease progression for all patients was 6.8 months. Myelosuppression was the most common treatment-related side effect. Severe neutropenia occurred in eight patients (24%) but was rarely associated with infectious complications. Severe leukopenia occurred in six patients (18%), and severe thrombocytopenia occurred in only one patient (3%). There were no grade 4 nonhematologic toxicities reported, and alopecia, which occurred in less than 10% of patients, was the only grade 3 toxicity.
Because the combination of docetaxel and gemcitabine produces a favorable response with a good tolerability profile and can be administered easily on an outpatient basis, the regimen should be studied for its ability to palliate symptoms, Dr. Hejna noted.
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