Northwestern University, Feinberg School of Medicine, Chicago, IL
Sangeetha Meda Reddy , Nancy Kwon , Robert Norm Harden , Judith A. Paice , Halla Sayed Nimeiri , Mary Frances Mulcahy , Al B. Benson III, Maxwell Thomas Vergo , Irene B. Helenowski
Background: Acute oxaliplatin neurotoxicity has been shown to be predictive of chronic neuropathy, a devastating irreversible adverse effect of oxaliplatin. Our study was designed to test the utility of quantitative sensory testing (QST) to measure acute oxaliplatin neurotoxicity at early time points to identify those at risk for developing chronic neuropathy. Methods: Gastrointestinal cancer patients receiving 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy were evaluated over a 1 year period for development of acute and chronic oxaliplatin neurotoxicity: before starting FOLFOX, 1 hour into oxaliplatin infusion, before cycles 2, 4 and 12, and 1 year after start of treatment. Patients underwent QST to measure thermal and mechanical sensitivities, vibration detection, pain sensation, and fine motor skills. Chronic neuropathy was measured using National Cancer Institute Common Toxicity Criteria for Adverse Events version 4. Results: We conducted analysis of 18 patients that have reached the 1 year followup period. We found thermal QST measured during cycle 1 infusion, which is indicative of acute neurotoxicity, to be predictive of 1 year neuropathy. Decreased cold detection intrainfusion during cycle 1 relative to baseline scores yielded a significant correlation to chronic neuropathy scores (rs= -0.53, p=0.03) and predicted grade 2 or 3 neuropathy (p=0.048). Furthermore, decreased cold detection scores intrainfusion showed trend towards correlation to neuropathy scores (rs= -0.45, p=0.07) and prediction of grade 2 or 3 neuropathy (p=0.07). Additionally, patients with higher tolerance to cold and heat intrainfusion were at higher risk for grade 1 or higher neuropathy (p=0.057 for cold pain, p=0.03 for heat pain). We also found decreased mechanical detection scores using von frey filaments as early as cycle 2 were correlated to 1 year neuropathy scores (rs=0.52, p=0.03) and predicted development of grade 2 or 3 neuropathy (p=0.008). Conclusions: We can use QST to identify high risk patients that are likely to develop chronic neuropathy at 1 year, allowing for targeted use of preventive measures to decrease the incidence of this debilitating adverse effect.
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