Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial

Abstract

To explore the impact of dose intensity (DI) in the adjuvant setting of breast cancer, a randomized phase III trial was conducted comparing postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide, methotrexate and fluorouracil (CMF)in high-risk breast cancer patients. From Oct 2000 to June 2005, 1,121 node-positive patients were randomized to dose-dense sequential epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, NJ) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of "intensified" combination chemotherapy with CMF. By protocol design total cumulative dose and duration of treatment were identical in both groups. Dose intensity of epirubicin and paclitaxel was double in the dose-dense arm. Prophylactic treatment with granulocyte colony-stimulating factor was given with the dose-dense treatments. Disease-free survival (DFS) was the primary endpoint. At a median follow-up of 76 months, 253 patients (23%) had documented disease relapse (123 vs. 130 in groups A and B, respectively) and 208 deaths (101, group A and 107, group B) had been observed. The 5-year DFS rate of 74 and 74% and OS rate of 86 and 85% were observed for group A and group B, respectively. No differences were found in DFS or OS between the two treatment groups (P = 0.78 and P = 0.45 for DFS and OS, respectively). Safety analysis results showing that both regimens were well tolerated and safe have been previously published (Fountzilas et al. Ann Oncol 2008). No DFS or OS benefit from the dose-dense sequential epirubicin and paclitaxel was detected when compared to the concurrent administration of the same drugs. No additional safety issues were raised with long-term follow-up.

Adjuvant Dose-Dense Chemotherapy for Breast Cancer: Available Evidence and Recent Updates

“…The Hellenic Cooperative Oncology Group (HeCOG) conducted a randomized trial in Greece with node-positive breast cancer patients (n = 1,121) [26]. Patients were randomized to receive i) epirubicin every 14 days for 3 cycles followed by paclitaxel every 14 days for 3 cycles and then 3 more cycles of intensified CMF every 14 days or ii) paclitaxel and epirubicin every 21 days for 4 cycles followed by intensified CMF every 14 days.…”

Updated Survival Analysis after a Median Follow-up of 12 Years of an Anthracycline-Containing Adjuvant Prospective Multicentre, Randomised Phase III Trial on Dose-Dense Chemotherapy in Primary Node-Positive, High-Risk Breast Cancer Patients

“…The Hellenic Cooperative Oncology Group HE 10/00 phase II trial [8] investigated comparable regimens as adjuvant treatment for node-positive breast cancer. After a median follow-up of 5 years, the DFS (74% for both arms) and OS rates (86% for the dose-dense arm vs. 85% for the standard-dose arm) in patients receiving either dose-dense E(110)-P(250) q2w -CMF q2w or standard-dose E(83)-P(187) q3w -CMF q2w were comparable.…”

“…Despite comparable OS rates to our analysis after 5 years, the DFS rates of our analysis were worse with 63% and 55% in the dose-dense and standard-dose arm, respectively. The differences might be due to differences in the lymph node status [4,8].…”

“…Studies investigating this aspect have published diverse results. Some phase III trials demonstrated an improved disease-free survival (DFS) and overall survival (OS) especially in patients with high tumour burden [3][4][5][6][7], whereas other studies failed to prove this advantage [8][9][10][11].…”

1976 Significance of PIK3CA mutations in patients with early breast cancer treated with adjuvant chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) study

“…The characteristics of these trials are described in brief in S1 Table and detailed information about them can be found in the respective original papers [11][12][13]. At that time, trastuzumab was not licensed as adjuvant treatment; however it was administered in HER2 positive patients upon relapse [14].…”