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The combination of epirubicin and taxol has proven to be a very active regimen in patients with metastatic breast cancer that can be used also in combination with G-CSF followed by collection of peripheral blood progenitor cells (PBPC). Another approach for optimizing the efficacy of epirubicin plus taxol is the combination with gemcitabine which can be used without G-CSF. based on this experience a new study was designed by an Italian working group in order to maximize complete response.

Background

GET is a new treatment regimen that has been developed by Dr. Pier Franco Conte and coworkers in Pisa, Italy. The rationale for choosing gemcitabine in addition to epirubicin and taxol was the favourable tolerability profile of this agent. A pilot study was performed to investigate efficacy and safety of this new treatment schedule including patients with metastatic breast cancer without having received prior chemotherapy for metastatic disease. Gemcitabine was adminstered in a dosage of 1000mg/m² (day 1 and 4), combined with epirubicin (90mg/m², day 1) and taxol (175mg/m², day 1). Prior adjuvant chemotherapy was allowed if no anthracyclines have been used within 6 months before study entry with the exception of epirubicin (max. cumulative dose 360mg/m²) and doxorubicin (max. cumulative dose 240mg/m²) provided that therapy had ended at least 1 month prior to study entry.

A total of 122 cycles were administered (100%) in this study whereby 4 cycles led to febrile neutropenia only. A delay of cycles due to neutropenia was observed in 12% and 11% of the cycles had to be reduced on the basis of neutropenia. Blood transfusion was required in one percent only. As to grade III/IV hematologic toxicity the most frequent side effect was neutropenia (37% and 30% of all cycles respectively). Related to the number of patients affected neutropenia emerged in 27% (grade III) and 59% (grade IV). Thrombocytopenia (grade III) was seen in 18% of the patients. Efficacy data were also promising according to Dr. Conte. An overall response rate of 86% was observed while complete response was achieved in 36%. 14% of the patients presented with stable disease.

GET and high-dose CT

Patients entering the study received 6-8 cycles of the GET regimen followed by idarubicin at a dosage of 40mg/m² and PBPC. If this does not lead to complete response patients are treated with another high-dose regimen consisting of thiothepa (600mg/m²), L-PAM (180mg/m²) and PBPC. So far 26 patients have been treated with this regimen including 13 patients with prior adjuvant chemotherapy. Metastatic disease was predominant at visceral sites (10 patients), soft tissue (6 patients) or bone (1 patient).

The efficacy analysis included 20 out of 26 patients who had received 6 cycles of the GET regimen. As to the response rates very promising results were observed, according to Dr. Conte.

The overall response rate was 90% and in 45% of the patients a complete response could be verified. An additional high-dose chemotherapy was used in 14 out of the 20 patients. 4 patients (2 CRs and 2 PRs) refused treatment with high?dose chemotherapy and therefore received 2 more cycles of the GET regimen (not included in efficacy analysis). Another 2 patients (1 CR , 1 SD) were still waiting for high-dose chemotherapy at the time of evaluation and are also not included in this analysis. Thus at this point of analysis there are 18 patients who had received the entire treatment program, including 4 patients with additional GET cycles instead of high-dose chemotherapy. In this subset of patients an overall response rate of 100% could be observed, with a complete remission in 61% after a median follow-up of 8 months. So far all the patients are alive and progression-free.

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