P3-14-02: Sequential Versus Upfront Intensified Neoadjuvant Chemotherapy in Patients with Large Resectable or Locally Advanced Breast Cancer (INTENS), Toxicity Results from a Phase III Study of the Dutch Breast Cancer Trialists' Group (BOOG).

Abstract

Abstract Background Taxanes have an established role as (neo-)adjuvant treatment of breast cancer. In the present study, we compared 4 AC - 4 T with 6 cycles of TAC in the neo-adjuvant setting (A=adriamycine, C=cyclophosphamide, T=docetaxel). Previously, we reported that AC-T resulted in a trend for improved outcome (odds ratio pCR of the breast 1.61; 95% CI 0.79−3.33). Now we report the safety data. Methods Women presenting with breast cancer, cT2≥3cm, cT3, cT4 and/or cN+, with measurable disease and no prior treatment, age ≥18 and ≤70 years and Karnofsky Score ≥70% were eligible. Patients were randomized to AC (60/600 mg/m2 q3wk x 4 cycles) followed by T (100 mg/m2 q3wk x 4 cycles) without primary G-CSF prophylaxis, or to TAC (75/50/500 mg/m2 q3wk x 6 cycles) with primary G-CSF prophylaxis. If indicated, trastuzumab and/or endocrine therapy were given as adjuvant treatment. This present analysis focuses on the toxicity profile of the two treatment arms. Results In total, 201 patients (n=100 AC-T, n=101 TAC) were included between February 2006 and April 2009. Baseline characteristics (AC-T/TAC) were well balanced. Patients in the AC-T arm had more frequently grade 3 / 4 toxicities as compared to the TAC arm, respectively in 57% and 28% (p=0.001). Grade 3 / 4 neutropenia without fever was more frequently reported with AC-T (35% vs. 4%; p=0.001). Grade 3 / 4 febrile neutropenia was also more frequent with AC-T (17% versus 5%; p=0.0062) and significantly increased during docetaxel treatment after AC. Notably, diarrhea was also more frequently seen in the AC-T arm (4% versus 0%, p=0.0423). Other grade 3 / 4 toxicities more frequently reported in the AC-T arm were neuropathy - sensory (5% vs. 0%; p=0.229) and pain other than muscle or bone pain (4% vs. 0%; p=0.0423). There were no grade 3 / 4 toxicities more frequently observed in the TAC arm. Conclusion In the comparison of two taxane-anthracycline-cyclophosphamide regimens in the neo-adjuvant setting, it is observed that the sequential approach with a lower cumulative dose tends to have a slightly better efficacy outcome, but at the cost of increased grade 3 / 4 toxicity. However, considering the use of primary G-CSF prophylaxis in the TAC arm, and the fact that the incidence of febrile neutropenia was higher during taxane containing chemotherapy in the AC-T arm, the difference might (partly) disappear if primary G-CSF prophylaxis would be used in the sequential arm. Primary G-CSF prophylaxis may be considered during docetaxel if used sequentially after anthracycline-containing chemotherapy. Support: Unrestricted grants from sanofi-aventis NL BV and Amgen BV. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-02.