Assessment and quantification of taxane-induced neurotoxicity in a phase III randomized trial of breast cancer (AC followed by PAC/DOC vs. PAC/DOC alone): N-SAS BC 02

Abstract

8523 Background: Chemotherapy-induced peripheral neuropathy (CIPN) commonly occurs during taxane chemotherapy (Tx). There is no standardized approach used in the assessment of CIPN. Physician-based instruments (e.g., NCI-CTC) are widely used for this purpose, but are associated with several important limitations. As current medical evidence suggests that physician-based assessments under-report the incidence and severity of subjective symptoms, they cannot reliably or accurately assess symptoms of CIPN. We prospectively assessed CIPN during Tx in a phase III randomized trial to evaluate the reliability and sensitivity of these different approaches. Methods: Three hundred breast cancer (BC) patients entered the National Surgical Adjuvant Study of Breast Cancer 02 (N-SAS BC 02), a phase III randomized trial comparing 4 cycles of AC followed by 4 cycles of Tx (paclitaxel [PAC] or docetaxel [DOC]) vs. 8 cycles of Tx alone in N+ BC patients after surgery. CIPN and QOL were secondary endpoints. Patient-based PNQ and FACT-Ntx were compared to the clinician-based NCI-CTC. Assessments were conducted at baseline, 3rd, 5th, 7th cycles, 8 months, and one year after starting adjuvant treatments. A linear mixed effect model was used to compare data in the two treatment groups across repeated cycles of treatment. Results: Average response rate of the instruments was > 90%. Sensory PNQ scores strongly correlated with sensory FACT-Ntx scores (r=0.70), while they weakly correlated (r=0.43) with NCI-CTC scores. NCI-CTC scores distributed between 0 and 2, while PNQ scores distributed between 0 and 4. Comparison of CIPN during the first 3 cycles showed that significantly higher overall incidence of sensory disturbance was observed in Tx compared with AC as assessed by both PNQ (PAC, P<0.0001; DOC, P=0.0007) and NCI-CTC (PAC, P<0.0001; DOC, P=0.0026). The PNQ appeared to detect more severe grades of sensory neuropathy compared to NCI-CTC. Conclusions: This study confirmed that physicians tended to underestimate CIPN, and patient-rated PNQ was a more reliable and valid instrument to assess CIPN. The development of new and reliable assessment methods would represent important medical advancements for cancer patients. [Table: see text]