gms | German Medical Science

Background: Dose dense chemotherapy has become a new treatment option in breast cancer patients (INT C9741, ETC trial). Long term survival and toxicity data of the two phase III trials are pending. We report the final results of the foregoing ETC phase I/II study with a median follow up of 6,5 years.

Methods: A multicenter phase I/II pilot study was conducted in Germany between 12/96 and 12/98. 102 patients with 4 9 positive lymph nodes were recruited, median age was 50 years. Patients received three courses each of epirubicin (120 150 mg/m2), paclitaxel (200 250 mg/m2) and cyclophosphamide (2.000 3.000 mg/m2) at seven different dose levels. Cycles were given at two weeks interval with G-CSF support (5g/kg, day 3 10).

Results: The median number of positive nodes was six. 90% of patients received all nine cycles. No cardiac toxicity was reported. Haematological toxicity was highest during treatment with cyclophosphamide and modest during treatment with paclitaxel. Grade III/IV neutropenia occured in 22,6% of epirubicin cycles, only in 1,7% of paclitaxel cycles and in 51,8% of cyclophosphamide cycles. 16 cases (16,7%) of febrile neutropenia were reported. Only one patient required platelets transfusion, but 26,4% of patients required red blood cell transfusion. Dose limiting non haematological toxicity (grade III neurotoxicity) was observed with paclitaxel (250 mg/m2) in 7/27 evaluable patients (25,9%). One patient experienced acute myelogenous leukemia. With a median follow up of 6,5 years, disease free survival is 73% and overall survival is 79%.

Conclusions: The final results of the ETC phase I/II trial confirm the acceptable long term toxicity of this regimen. Disease free survival and overall survival show very promising data in this high risk group of patients. The results of the long term follow up (6,5 years) correspond with the preliminary results of the ETC phase III trial reported at ASCO 2004.