AbstractCancer-induced bone pain (CIBP) is a significant health problem in the USA and the rest of the world. With theimprovement of treatment options to manage cancer a greater number of cancer patients are now living longeryet experiencing chronic pain. Metastasis to the bones inflicts severe and debilitating pain. The golden standardpharmaceutical agent to manage pain is opioids. Cancer patients need to take increasing doses of opioids tocontrol their pain. Sadly opioids come with significant side effects. Many attempts have been made to createbetter regiments for pain control while reducing opioids yet most patients are simply not achieving better controlof CIBP. Eliminating opioids entirely is not a reasonable approach. A better approach for controlling CIBP andlower opioids would be to add a non-opioid agent that has different mechanism(s) of action. This may bettercontrol pain while lowering opioids needed resulting in the reduction of side effects. Sulfasalazine is suchpossibility. It is an anti-inflammatory drug with an established safety profile. It has been in use for over fifty yearsfor the treatment of some inflammatory conditions. In addition sulfasalazine has the capacity to decrease thesurvival of cancer cells and also to lower the amount of inflammatory mediators. Sulfasalazine inhibits the influxof cysteine and the efflux of glutamate from cancer cells. Cysteine is needed for cell survival against oxidativestress while extracellular glutamate activates pain receptors. Therefore sulfasalazine will act as an anti-inflammatory agent an agent to accelerate cancer cells damage and decrease the release of glutamate thatactivates pain fibers. This one agent with three mechanisms of actions may lower the amount of opioids neededfor patients with CIBP. Lowering of opioid dosing will decrease unwanted side effects. The purpose of this clinicaltrial is to co-administer sulfasalazine with opioids to patients with CIBP and characterize their opioid use and theimprovement of their pain. Our central hypothesis is that adding sulfasalazine to the opioid pain medicationregiment will reduce the amount of opioids used resulting in a reduction in opioid-induced side effectswhile reducing pain and improving the overall quality of life. We also predict that sulfasalazine may reducethe inflammatory mediators as well as tumor markers in the serum. This study will be conducted in a double-blind randomized fashion with two independent but related specific aims (SA) and one exploratory aim (EA).We will assess whether sulfasalazine will improve both of our primary and secondary outcomes. Our primaryoutcome is reduction in opioids. The secondary outcome is reduction in pain and improvement of the quality oflife (SA1). Secondly we will assess the levels of serum glutamate and IL-6 TNF-alpha and tumor markers beforeand after treatment with sulfasalazine (SA2). We expect sulfasalazine to decrease inflammatory mediators.Thirdly we will assess the levels of serum tumor markers before and after treatment with sulfasalazine andcorrelate with tumor imaging studies (EA1). We expect sulfasalazine to decrease plasma tumor markers. Thedata obtained may provide physicians with additional options to manage CIBP patients.