TANDEM HIGH-DOSE THERAPY WITH IFOSFAMIDE, EPIRUBICIN, CARBOPLATIN ANDPERIPHERAL-BLOOD STEM-CELL SUPPORT IS AN EFFECTIVE ADJUVANT TREATMENTFOR HIGH-RISK PRIMARY BREAST-CANCER
R. Haas et al., TANDEM HIGH-DOSE THERAPY WITH IFOSFAMIDE, EPIRUBICIN, CARBOPLATIN ANDPERIPHERAL-BLOOD STEM-CELL SUPPORT IS AN EFFECTIVE ADJUVANT TREATMENTFOR HIGH-RISK PRIMARY BREAST-CANCER, European journal of cancer, 33(3), 1997, pp. 372-378
We evaluated the therapeutic efficacy and toxicity of a tandem high-do
se therapy with peripheral blood stem cell (PBSC) support in 40 patien
ts with high-risk, primary breast cancer (stage IT-III) and involvemen
t of ten or more positive axillary lymph nodes. Their median age was 4
4 years (range 23-56), Two cycles of cytotoxic chemotherapy with ifosf
amide (10000 mg/m(2)) and epirubicin (100 mg/m(2)) were administered.
Granulocyte colony-stimulating factor (G-CSF) was given to hasten neut
rophil reconstitution and to mobilise PBSC during marrow recovery. Leu
kaphereses were performed following the first and/or second cycle. Tan
dem high-dose therapy consisted of two cycles with ifosfamide (15 or 1
2 g/m(2)) and epirubicin (150 mg/m(2)), while carboplatin (900 mg/m(2)
) was added for the last 24 patients included. Using an immunocytochem
ical method, two of 11 patients had cytokeratin-positive tumour cells
in three leukapheresis products that were collected following the firs
t G-CSF-supported cycle with ifosfamide and epirubicin, whereas only t
wo harvests obtained following the second cycle in 26 patients contain
ed cytokeratin-positive tumour cells. The number of CD34+ cells/kg re-
infused following both high-dose cycles was similar (4.20+/-0.29 x 10(
6), first cycle and 5.25 +/- 0.63 x 10(6), second cycle), and no notab
le difference was noted in the speed of haematological reconstitution.
An absolute neutrophil count (ANC) of 0.5 x 10(9)/l was reached after
a median time of 13 days, while an unsupported platelet count of 20.0
x 10(9)/l was achieved after a median time of 8 (first, cycle) and 9
(second cycle) days post-transplantation. Patients autografted with mo
re than 7.5 x 10(6) CD34+ cells/kg had platelet counts above 20 x 10(9
)/l within less than 10 days. 6 patients relapsed between 7 and 11 mon
ths (median 8 months) post-transplantation. 37 patients are alive and
in remission with a median follow-anp time of 11 months (range 1-38).
This translates into a probability of disease-free survival (DFS) of 7
7% (95% CI 32-95%) at 38 months. The probability of overall survival.
is 85%, since 3 patients with local relapse achieved, a second complet
e remission following surgery and involved-field radiotherapy. In conc
lusion, a sequential high-dose therapy including ifosfamide, epirubici
n, carboplatin and PBSC support is well tolerated and effective in pat
ients with high-risk primary breast cancer. Involved-field irradiation
should be performed post-transplantation to reduce the risk of local
relapse. (C) 1997 Elsevier Science Ltd.