Combination of Docetaxel and Gemcitabine Effective in Non-Small-Cell Lung Cancer

February 1, 2001

The combination of docetaxel (Taxotere) and 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

The combination ofdocetaxel (Taxotere) and gemcitabine (Gemzar) is active as first-line therapy foradvanced, metastatic non-small-cell lung cancer and appears to be generallywell tolerated, according to the results of a phase II study published in arecent issue of Cancer (89:516-522, 2000).

Of 34 patients, 15 (44%) had a partial response to treatmentand 2 (6%) had a complete response, for an overall response rate of 50%. Themedian 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 6months. Myelosuppression was the most common adverse reaction, but was usuallynot severe.

"We have not yet identified the optimal regimen for useas standard therapy in patients with advanced non-small-cell lung cancer, andthere is a strong need for an alternative to conventional cisplatin[Platinol]-based chemotherapy," said Michael Hejna, MD, department ofinternal medicine, division of oncology, University Hospital of Vienna, Austria,and the study’s principal investigator. "Our finding that the combinationof docetaxel and gemcitabine provides a good overall response rate with aparticularly impressive survival rate given our patients’ poor health statusis very encouraging."

Patient Characteristics and Dosing Schedule

Participants included 34 patients with advanced, measurablenon-small-cell lung cancer who had not undergone prior chemotherapy and whohad a life expectancy of at least 3 months. Three patients had stage IIIBdisease, and 31 patients had stage IV disease; 24 (71%) had a World HealthOrganization performance status of 1 or 2, and 21(62%) had involvement of morethan two organs. The median age of study participants was 61 years, with 16patients (47%) over the age of 65 years.

"The rationale for combining these two drugs includedtheir distinct mechanisms of action with different intracellular targets, highlevels of single-agent activity in non-small-cell lung cancer, and recentlypublished data in various tumor types, suggesting potential drug synergismbetween the taxanes and gemcitabine," said the study authors.

All patients received docetaxel at 80 mg/m2administered intravenously over 90 minutes on day 1 and gemcitabine at 1,000mg/m2administered on days 1 and 10. Granulocyte colony-stimulating factor (G-CSF[Neupogen]), 5 µg/kg, was administered subcutaneously once a day on days 2through 8. Treatment cycles were repeated every 3 weeks for a maximum of sixcycles. A total of 163 cycles of treatment were administered throughout theinvestigation.

Study Results

The median duration of response to treatment was6.5 months, and the median time to disease progression for all patients was6.8 months. Myelosuppression was the most common treatment-related side effect.Severe neutropenia occurred in eight patients (24%) but was rarely associatedwith infectious complications. Severe leukopenia occurred in six patients (18%),and severe thrombocytopenia occurred in only one patient (3%). There were nograde 4 nonhematologic toxicities reported, and alopecia, which occurred in lessthan 10% of patients, was the only grade 3 toxicity.

Because the combination of docetaxel and gemcitabine producesa favorable response with a good tolerability profile and can be administeredeasily on an outpatient basis, the regimen should be studied for its ability topalliate symptoms, Dr. Hejna noted.