Abstract
513 Background: Dose-dense chemotherapy will become a new treatment option in breast cancer patients (pts) (INT C9741). Here we report the initial results of a second prospective randomized trial that compares dose-dense vs. conventionally scheduled sequential chemotherapy in high-risk node positive pts. Methods: A multi-center phase-III trial of the German “Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO)” recruited 1284 pts from 12/98 until 4/03. Pts below 65 years of age were eligible if they had at least 4 involved axillary lymph nodes. In the experimental arm, pts were assigned to receive three courses each of epirubicin(150 mg/m2), paclitaxel (225 mg/m2) and cyclophosphamide (2500 mg/m2) at 2 weeks interval (q2wks) (ETC) with G-CSF support (5μg/kg/SC day 3–10). A second randomization ± Epoetin-alpha was performed (150 IU/kg/SC three times weekly). In the standard arm 4 courses of conventional dosed epirubicin/cyclophosphamide (90/600 mg/m2) followed by 4 courses of paclitaxel (175 mg/m2) (q3wks) were given. Results: Median patient age was 50 years. Risk factors were well balanced in both arms. 59% and 41% of the pts had 4–9 and ≥10 infiltrated nodes. The median number of positive nodes was 8. In this second interim analysis 1169 pts were fully evaluable. No unusual toxicities were seen, especially no severe cardiotoxicity. Hematological toxicity (anemia, neutropenia and thrombopenia) was more frequent in the ETC arm (p<0,0001) and varied distinctly between drugs. The incidence was highest during treatment with cyclophosphamide and lowest during treatment with paclitaxel. 7% of pts in the ETC arm vs. 2% in the standard arm were hospitalized for febrile neutropenia (p<0,0001). There were no treatment-related deaths during therapy. 82% of pts in the ETC arm vs. 90% in the standard arm received the planned number of cycles. The number of dose reductions was relatively small, ranging from 6,5% on the ETC arm to 2% on the standard arm. At a median follow-up of 28 months 94 pts in the ETC arm vs. 127 pts in the standard arm had relapsed. This difference was highly significant in the two-sided log-rank test (p=0,0009) with a HR of 0,64 (95% CI: 0,49–0,83). Estimated 3-year RFS is 80% in the ETC arm vs. 70% in the standard arm. 103 pts have died (43 events vs. 60 events) favoring again the ETC arm (two-sided log-rank test: p=0,030; HR: 0,65 (95% CI: 0,44–0,96). Estimated 3-year OAS is 90% in the ETC arm vs. 87% in the standard arm. There was a highly significant difference in anemia grade 1–4 as well as in the number of RBC's transfusions between ETC ± Epoetin alpha (p<0,0001). No difference in DFS (p=0,84) or OAS (p=0,98) was found between ETC ± Epoetin alpha. Conclusions: Evidence to date indicates that the dose-dense ETC-regimen as adjuvant therapy in high-risk breast cancer pts is well tolerated and significantly improves DFS and OAS. Confirming the results of INT C9741, dose-dense sequential regimens may become a future standard option in the adjuvant treatment of node positive breast cancer pts. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb; Amgen; Pharmacia; Ortho-Biotech
Published Version
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