Background: Approximately 20% to 40% of patients with cancer who receive neurotoxic chemotherapy will develop painful chemotherapy-induced peripheral neuropathy. Smith et. al firstly reported that duloxetine was effective on above neuropathy after taxanes and platinums (JAMA 2013), so we planed to evaluate the duloxetine effect in Japanese patients after above drugs and more expanding drugs include vinca alkaloids and bortezomib. Methods: Patients were randomized to receive either duloxetine followed by vitamin(V)B12 or VB12 by duloxetine. The initial treatment consisted of 20 mg of duloxetine or 1.5g VB12 for the first week and 40mg of duloxetine or VB12 daily for 3 additional weeks (an open label, randomized, crossover). Dose reduction by the adverse effects was permitted. The primary hypothesis was that duloxetine would be more effective than VB12 in decreasing chemotherapy-induced peripheral neuropathic pain. Numbness and Pain severity were assessed weekly using visual analogue scale (VAS). This research was approved by the Research Ethics Committee of Higashi Sapporo Hospital and University Hospital Medical Information Network (UMIN) Center in Japan.Thirty-four cases (Breast cancer: taxanes 2, gastric cancer: taxane 5, colon cancer: oxaliplatin 6, Malignant lymphoma: vincristine 13, multiple myeloma: bortezomib 8) were made an entry in our institution. Five cases dropped out because of the adverse effect with sleepy and general malaise. Results: Obvious improvements of VAS scores of numbness and pain were observed in duloxetine group. Significant differences of delta VAS (pre VAS scale – 4 weeks VAS after drug administration) were observed between duloxetine group and VB12 group in the aspect of numbness (p=0.02) and pain (p=0.03). Conclusions: Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with VB12 for 4 weeks resulted in a reduction in numbness and pain, but there are many cases with drop out by the adverse effects. Clinical trial information: 000011554.