Pain is the most prevalent symptom in cancer patients, and bone metastasis is one of the most common sources of cancer-related pain. In the 3-step guidelines established by the World Health Organization (WHO) non-opioid analgesics (acetaminophen and NSAIDs) are the first step against cancer pain. In step 2, when pain relief is not achieved with non-opioid medications, synergistic opioid/non-opioid combinations (e.g., codeine + acetaminophen) are used. Thus, acetaminophen is a heavily used efficacious treatment for bone cancer-related pain. However, it has been recognized that even at therapeutic doses acetaminophen causes liver toxicity. Cancer patients are exposed to a multitude of chemotherapeutics that tax liver function to the limit, and thus are particularly susceptible to acetaminophen-induced liver toxicity. Therefore, an acetaminophen-like analgesic that does not deplete glutathione stores would increase the ability to treat cancer-related pain with Step 1 and Step 2 medications, and fill an important void in the options available to cancer patients. We are currently exploring a series of new and proprietary derivatives of acetaminophen, in which the lead compound (SCP-1) has good oral efficacy that is synergistic with opioids, and appears to overcome the hepatotoxic shortcomings of acetaminophen. Under this Phase I SBIR project, we will determine the feasibility of using this unique compound as stage 1 and stage 2 treatments of bone cancer pain.
