Results presented at the 2006 San Antonio Breast Cancer Symposium (SABCS) continue to demonstrate efficacy of dose-dense chemotherapy over standard doses in early breast cancer.

Dose-dense chemotherapy, or shortening the interval between chemotherapy doses, has demonstrated improvement in outcomes compared to conventional-dose chemotherapy in patients with high-risk, early breast cancer. Due to concerns regarding toxicity associated with dose-dense therapy, long-term follow-up from comparative trials, including dose-dense therapy, continues.

Researchers affiliated with the German AGO Group conducted a multicenter phase III trial directly comparing dose-dense chemotherapy to conventional chemotherapy in high-risk early breast cancer patients. This trial enrolled 1,284 patients below the age of 65 years who had at least 4 involved axillary lymph nodes. Patients were randomized to dose-dense therapy (epirubicin 150 mg/m2, paclitaxel 225 mg/m2 and cyclophosphamide 2500 mg/m2) administered once every 2 weeks with granulocyte colony stimulating factor (G-CSF) support, or conventional therapy (four courses of conventional dosed epirubicin, cyclophosphamide followed by four courses of paclitaxel every 4 weeks. Median age of patients was 51 years, and the median number of positive nodes was 8. 

• Results from the third interim analysis of this trial included 1,255 evaluable patients.
• There were no treatment-related deaths during therapy.
• At 5 years, relapse-free survival was 70% in the dose-dense arm, compared with 62% in the conventional-dose arm (p=0.0285).
• At 5 years, overall survival was 82% in the dose-dense arm, and 77% in the conventional-dose arm.
• Quality of life declined during dose-dense therapy, but was recovered 3 months following completion of therapy.
• 7% of patients in the dose-dense arm were hospitalized for febrile neutropenia, compared with just 2% in the conventional-dose arm (p<0.0001).
• There was no severe cardiotoxicity, and no unusual toxicities noted.

The researchers concluded that longer follow-up continues to demonstrate a significant improvement in relapse-free survival for dose-dense chemotherapy compared to conventional-dose chemotherapy in high-risk early breast cancer patients. With the progression of newer agents emerging into earlier-stage settings, however, risks and benefits of dose-dense therapy must be weighed. However, the authors stated that “dose-dense chemotherapy will become a standard of care in the adjuvant treatment of high-risk breast cancer patients”.

Reference: Moebus V, Leuck H, Thomssen C, et al. Dose-Dense Sequential Chemotherapy with Epirubicin (E), Paclitaxel (T) and Cyclophosphamide (C ) (ETC) in Comparison to Conventional Dosed Chemotherapy in High-Risk Breast Cancer Patients (> (or equal to) LN), Mature Results of an AGO-Trial. Proceedings from the 2006 San Antonio Breast Cancer Symposium. San Antonio, Texas. Oral presentation December 17, 2006. Abstract # 53.