Temporal, Location- and Symptom-Specific Likelihood of Patient-Reported Sensory Symptoms Related to Oxaliplatin-Induced Peripheral Neuropathy (OIPN) in Patients Receiving Oxaliplatin for Three Months

SIMPLE SUMMARY: There are no known effective preventative interventions for oxaliplatin-induced peripheral neuropathy (OIPN) sensory symptoms of numbness, tingling and pain other than limiting drug exposure. With the shorter 3-month duration of oxaliplatin increasingly being used, compared to the previous 6-month standard, we were motivated to quantify the temporal, location- and symptom-specific likelihood of patient-reported sensory symptoms related to OIPN in 141 patients from the placebo arms of two multisite OIPN prevention trials exposed to oxaliplatin for 3 months. Despite a shorter duration of oxaliplatin, we show that OIPN was still pervasive, with patients experiencing considerable mild to moderate numbness and tingling in the lower and upper distal extremities. To avoid the debilitating sequelae from OIPN and to ensure that patients continue to receive the most efficacious doses of oxaliplatin, identification of effective OIPN preventative interventions is still needed, regardless of whether oxaliplatin is planned to be given for 3 versus 6 months. ABSTRACT: While oxaliplatin-induced peripheral neuropathy (OIPN) is more common and severe in patients who receive the previous standard, 6-month oxaliplatin-based treatment, we hypothesized that OIPN was still pervasive in patients who received shorter, 3-month-treatment regimens. Using six EORTC QLQ-CIPN20 questions that quantify numbness (N), tingling (T) and shooting/burning pain (P) in upper/lower distal extremities, our aim is to quantify patient-reported responses over 3 months (6 cycles) of oxaliplatin regarding symptom-specific timing, location and severity. For each question, patients were asked how each of the sensory symptoms had affected them during the preceding week, with 1 = “Not at all”, 2 = “A little”, 3 = “Quite a bit” and 4 = “Very much”. The proportional odds model for the cumulative log odds of response that allowed symptom-specific patient heterogeneity to be obtained was applied to a pooled dataset from the placebo arms of two multisite OIPN prevention trials and fit separately to the upper/lower distal extremities. For each symptom, we report the cycle-specific marginal probabilities for each response. In 141 patients, substantial patient heterogeneity in the likelihood, at a given cycle, of a more severe response for a symptom was present. Distinct patterns in the probabilities for each response over time for N and T were observed between the upper/lower distal extremities, while the probabilities of a response >1 for P was largely negligible in both locations. Despite the decrease in exposure to oxaliplatin from 6 to 3 months, OIPN was still pervasive with patients experiencing considerable N and T in the fingers (or hands) and toes (or feet).