Tramadol/Acetaminophen Combination Tablets in Cancer Patients with Chemotherapy-Induced Peripheral Neuropathy: A Single-Arm Phase II Study

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent complication in patients receiving anticancer chemotherapy, but no effective treatment is yet available. Objective: To evaluate the efficacy and safety of a tramadol/acetaminophen combination tablets for CIPN. Design: This is a single-arm phase II study of tramadol/acetaminophen. Setting/subjects: Eligible patients had received oxaliplatin, paclitaxel, or nab-paclitaxel, and were experiencing CIPN. The patients were given one tablet (37.5?mg tramadol plus 325?mg acetaminophen) twice a day for 7 days, then four times a day for 21 days. Measurements: The primary endpoint was the numerical rating scale of neuropathic pain. Other endpoints included the potential of CYP2D6 genetic variants to effective response or toxicity. Results: Of the 34 patients enrolled, 23 completed the protocol treatment. The mean neuropathic pain score decreased insignificantly from 5.53 at baseline to 5.00 at 28 days (95% confidence interval ?0.21 to 1.43; p?=?0.139). However, 13 of the 23 (56.5%) patients who completed the protocol treatment showed improvement of the neuropathic pain score by at least 1 point. No severe adverse events were observed. Tramadol/acetaminophen may be more effective in patients with the intermediate metabolizer phenotype of the CYP2D6 single nucleotide polymorphisms (SNPs) although at the cost of increased toxicity. Conclusions: Although tramadol/acetaminophen tablets did not reduce neuropathic pain to a statistically significant degree, the neuropathic pain severity reduced in more than a half of the patients.