PISA, ITALYGemcitabine, 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