RT Journal Article
SR Electronic
T1 Sequential Administration of Epirubicin and Paclitaxel for Advanced Breast Cancer. A Phase I Randomised Trial
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1211
OP 1217
VO 25
IS 2B
A1 C. FOCAN
A1 M.P. GRAAS
A1 M. BEAUDUIN
A1 J.L. CANON
A1 J.P. SALMON
A1 G. JERUSALEM
A1 D. FOCAN-HENRARD
A1 J.P. LOBELLE
A1 D. SCHALLIER
YR 2005
UL http://ar.iiarjournals.org/content/25/2B/1211.abstract
AB Forty-six previously untreated patients with advanced breast cancer were eligible for the present randomised phase I study. It aimed to evaluate the toxicity and activity of a therapeutic sequence with epirubicin on day 1 followed by paclitaxel on day 2 (sequence A) or the reverse sequence, i.e., paclitaxel on day 1 followed by epirubicin on day 2 (sequence B). The starting doses of epirubicin and paclitaxel, administered either according to sequence A or B, (level 1 cohort) were 90 mg/m2 and 175 mg/m2, respectively. Per cohort of 3 patients, the dose of paclitaxel was increased by 25 mg/m2 (levels 2 and 4) and of epirubicin by 10 mg/m2 (levels 3 and 5). Treatment was repeated with 3-week intervals. The maximal tolerated dose (MTD) was achieved at level 1 in sequence B (paclitaxel first) and level 3 (epirubicin100 mg/m2 followed by paclitaxel 200 mg m2) in sequence A. Dose limiting toxicity (DLT) was neutropenia (+/- febrile) in both sequences. Cardiac events occurred in 28% of the patients; significant decrease in left ventricular ejection function (LVEF) was observed in 8/33 and in 2/13 patients in sequence A and B, respectively. This was associated with 5 and 1 cardiac heart failure (CHF), respectively. In 43 evaluable patients, 10 CR and 25 PR were observed (overall response rate 81%). In the 20 patients with locally advanced disease (LABC), the respective numbers were 7 CR and 11 PR; in the 23 metastatic (MBC) patients, 3 CR and 14 PR were recorded. The median survival of the both groups was not reached at 33 + months. In conclusion, the combination of epirubicin and paclitaxel has significant activity in breast cancer. The recommended sequence of both drugs in combination therapy, mainly to avoid neutropenia, is epirubicin day 1 followed by paclitaxel on day 2. Cardiac toxicity remains problematic in either sequence of administration. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved