FLOX (5-fluorouracil + leucovorin + oxaliplatin) chemotherapy for colorectal cancer leads to long-term orofacial neurotoxicity: a STROBE-guided longitudinal prospective study

Background: Colorectal carcinoma (CRC) is widely treated by chemotherapy based on an intensely neurotoxic drug: oxaliplatin (OXL). We objective to evaluate prospectively the orofacial neurotoxicity during FLOX (fluorouracil + leucovorin + OXL) chemotherapy. Methods: So, 46 patients with CRC were prospectively evaluated during FLOX chemotherapy by 3 cycles (C) of 6 weeks (W) each. We weekly applied the orofacial section of the Acute and Chronic Neuropathy Questionnaire of Common Toxicity Criteria for Adverse Events of the National Cancer Institute of the United States of America (Oxaliplatin-specific neurotoxicity scale). Patients were asked the following concerning the severity (scores 0–5) of orofacial symptoms: jaw pain, eyelids drooping, throat discomfort, ear pain, tingling in mouth, difficulty with speech, burning or discomfort of the eyes, loss of any vision, feeling shock/pain down back and problems breathing. We summed the scores (0–50) and evaluated the clinicopathological data. Friedman/Dunn, Chi square and multinomial regression logistic tests were used (SPSS 20.0, p < 0.05). Results: There was a significant increase in sum of orofacial neurotoxicity from baseline to C1.W3, C2.W1 and C3.W5 (p < 0.001) due increase in scores of jaw pain (p < 0.001), eyelids drooping (p = 0.034), throat discomfort (p < 0.001), ear pain (p = 0.034), tingling in mouth (p = 0.015), burning/discomfort of your eyes (p < 0.001), loss of any vision (p < 0.001), feeling shock/pain down back (p < 0.001), problems with breathing (p = 0.045), but not difficulty with speech (p = 0.087). Women (p = 0.021) and young patients (p = 0.027) had significant higher prevalence of orofacial neurotoxicity. Conclusions: FLOX-related orofacial neurotoxicity begins acutely and remains long term with increased incidence in women and younger patients.