Gemcitabine/Epirubicin/Paclitaxel Regimen Highly Active in Previously Treated Metastatic Breast Cancer

PISA, ITALY—Gemcitabine, epirubicin, and paclitaxel (GET) is a highly active regimen in previously treated metastatic breast cancer, Pierfranco Conte, MD, reported at a clinical investigators’ workshop sponsored by the University of Texas M. D. Anderson Cancer Center and Pharmacia Oncology. Dr. Conte is Chief of the Division of Medical Oncology at St. Chiara Hospital in Pisa, Italy.

The GET regimen includes gemcitabine (Gemzar) 1,000 mg/m² on days 1 and 4, epirubicin (Ellence) 90 mg/m² on day 1, and paclitaxel (Taxol) 175 mg/m² on day 1. Cycles repeat every 3 weeks for up to eight courses. Dr. Conte said that one advantage of this combination is that the combination produces higher plasma concentrations of the active metabolite epirubicinol than similar doses of epirubicin given alone.

GET was studied in 36 patients with stage IV metastatic breast cancer. Eighteen had prior adjuvant chemotherapy, two had prior anthracycline treatment, and two had prior hormonal therapy for metastasis. Median recurrence-free survival had been 36 months, and dominant metastatic sites were the viscera (23), soft tissues (10), and bone (3). Sixteen of 36 patients had three or more involved sites.

Dr. Conte reported an overall response rate of 92% (33/36), including complete responses in 31% of patients (11/36). He said that by comparison, the response rate after high-dose chemotherapy is about 96%, with 58% complete responses.

The GET regimen, which was given without growth factor support, caused grade 4 neutropenia in 305 courses, but there were only two episodes of febrile neutropenia. Grade 4 thrombocytopenia occurred in 6% of courses, but only two patients required platelet transfusions. There were no grade 4 nonhematologic toxicities, but alopecia was “universal.” Dose delays were required in 24% of courses, most for about 1 week.

“At median follow-up of more than 2 years, median progression-free survival is 19.4 months, and median overall survival has not yet been reached,” Dr. Conte said.

Multicenter GET Study

The regimen was subsequently studied in a multicenter trial of 39 patients. Dr. Conte said that in this study there were dose delays in 205 cycles, dose reductions in 16%, and episodes of febrile neutropenia in 5% of cases, all in patients who had received at least two prior courses of chemotherapy. The response rate was 58%, including 10% complete responses.

The GET regimen is now being tested as first-line therapy in a phase III trial of GET vs epirubicin/paclitaxel for metastatic breast cancer, as primary chemotherapy in a phase II study of patients with tumors of 3 cm or larger, and as adjuvant therapy compared to epirubicin/cyclophosphamide followed by paclitaxel in a phase III trial of patients with four or more positive nodes.

Dr. Conte also discussed the question of using anthracyclines again after relapse from an anthracycline-based regimen. He said that median overall survival with etoposide/paclitaxel in patients previously treated with 5-fluorouracil/epirubicin/cyclophosphamide was slightly less than in those without prior treatment (24.7 months vs 27.5 months), but still clinically significant. Progression-free survival was a median 12.4 months in previously treated patients vs 15.4 months in those who had not undergone prior adjuvant anthracycline treatment.