Abstract P4-11-05: Acute and Late Toxicity Results from the SECRAB Trial: The Optimal SEquencing of Adjuvant Chemotherapy (CT) and RAdiotherapy (RT) in Early Breast Cancer (EBC)

Abstract

Abstract Background: SECRAB is a large multicentre randomised controlled trial designed to determine the optimal sequence of CT and RT for women with EBC. The second objective of this trial was to determine if CT and RT treatment modalities could be given together without increased toxicity or compromising either modality. See abstract no 851519 for details of CT and RT scheduling. Methods: Data on acute skin reaction was collected on completion of RT and graded as mild, moderate or severe. Late toxicity data was collected annually and included lymphoedema, telangiectasia, severe subcutaneous fibrosis, brachial plexopathy, rib fracture, ischaemic heart disease, symptomatic lung fibrosis, and clinical radiation pneumonitis. Results: Between Jul 98 and Mar 04, 2296 women were randomised. Acute toxicity data was collected on 2267 patients who received RT. The distribution of RT schedules was balanced across treatment arms, with the majority of patients (67%) receiving 40Gy/15F (15F). Significantly more patients in the Syn arm experienced a delay of >10 days in CT delivery (11% vs 5%, p < 0.0001). Very few patients experienced a >7 days delay in RT in either arm (Syn n=12 vs Seq n=3). In a sub-set of 880 patients dose intensity of CT was not significantly different between the two arms. Percentage skin toxicities for the Syn and Seq arms respectively were: None 22.9 vs 36.3; Mild 52.4 vs 48.1; Moderate 20.2 vs 13.6; Severe 3.8 vs 1.1. A significantly (p < 0.001) higher proportion of patients on the Syn arm suffered a moderate or severe skin reaction compared to those on the Seq arm. An unplanned exploratory analysis by duration of RT showed that patients receiving >15F (45Gy/20F or 50Gy/25F) had a significantly worse acute skin reaction than those receiving 15F (25% vs 16%, p=<0.001). 5 patients on the Syn arm were admitted to hospital as a result of a severe RT reaction, 3 received >15F. Acute radiation pneumonitis was 0.3% in both arms (n=5 in total). Percentage late toxicities for the Syn and Seq arms respectively were not significantly different for: moderate/severe lymphoedema 6.1 (n=70) vs 5.5 (n=64); severe subcutaneous fibrosis 1.3 (n= 15) vs 0.6 (n=7); brachial plexopathy 0.2 (n=2) vs 0.1 (n=1); rib fracture 0.6 (n=7) vs 0.4 (n=5); ischaemic heart disease 0.4 (n=5) vs 0.4 (n=2); symptomatic lung fibrosis 0.3 (n=15) vs 0.3 (n=7); and late clinical radiation pneumonitis 0.1 (n=1) vs 0.1 (n=1). Howevermoderate/severe telangiectasia was 2.5% vs 1.3% in the Syn and Seq arms respectively (p =0.05). This difference was not seen in patients receiving 15F. Conclusions: The delivery of Syn CT-RT in the adjuvant treatment of EBC is associated with an increase in acute skin toxicity however the percentage of severe reactions is less than 5%. These skin reactions were seen predominantly in patients treated with concurrent RT (>15F). An increase in late skin telangiectasia was also seen in patients receiving >15F. There was no difference in other late toxicities recorded. Syn CT-RT is feasible in the adjuvant treatment of EBC and does not result in a reduction in dose intensity of delivered CT. The optimal schedule is 40Gy/15F which is now the standard regime used in the UK. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-05.