A comparison of simple single-item measures and the common toxicity criteria in detecting the onset of oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer

Abstract

8087 Background: Peripheral neuropathy (PN) is a common and intrusive side effect of chemotherapy. The assessment of PN is typically done via the common toxicity criteria (CTC). To date there is no optimal measure of peripheral neuropathy. We developed simple single-item numerical analogue scale (NAS) assessments for the unique oxaliplatin-induced PN. The purpose of this investigation was to asses the relative sensitivity of the CTC and NAS measures in detecting the onset and severity of PN in patients receiving oxaliplatin. Methods: 696 patients randomized to the FOLFOX4 arm of the the practice-changing inter-group/NCCTG study N9741 provided data on the incidence and severity of PN experienced via bi-weekly CTC assessments and NAS measurements taken every 12 weeks. The NAS is a simple measure from 0 representing no PN to 10 representing PN as bad as it can be. A change of 2 points from baseline on the NAS was used as a conservative estimate of a clinically meaningful change in PN. Results: 276 patients (40%) reported a 2 point worsening from baseline in PN via NAS compared to 256 (37%) with a CTC reported grade 2+ PN and 99 (14%) with a CTC reported grade 3+ PN. For those ultimately reporting PN, median dose to onset of a clinically significant worsening of PN via NAS was 424 mg/m2 relative to a dose to grade 2+ (3+) PN of 765 (961) mg/m2 for CTC criteria. This means that patients notice an increase in PN about two or three months earlier via the NAS relative to the CTC. Agreement between CTC grade 2+ (3+) PN and NAS assessment was only 65% (63%) with a Cohen’s Kappa of 0.26 (0.13). The majority of patients reported the 2 point decline in PN via NAS prior to their reported CTC PN event (53% for grade 2+, 83% for grade 3+). Conclusions: The CTC measurement of PN under-reports the incidence and time to onset of PN relative to simple single-item NAS measures. Grade 2 PN via the CTC is a clinically significant problem according to patient ratings on the NAS. In future studies, it is recommended that the CTC be supplemented by patient-reported measures of PN. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi, sanofi-aventis Sanofi, sanofi-aventis