Opioid Resistance Associated with CYP3A4 Hyperactivity and COMT Polymorphism in an Oncological Patient

We describe an interesting case of opioid unresponsive- ness, showing the importance of clinical history, inte- grated with pharmacokinetic and pharmacogenomic analysis, to shed light on mechanisms of abnormal response to opioid analgesics and provide clinicians with strategies to overcome opioid resistance. A 71- year-old woman (height 1.55 m, weight 48 kg) of Italian Slovene descent with endometrial carcinoma (staging pT3aN1Mx IIIC), who refused adjuvant chemotherapy and radiotherapy, showed a high bone, spinal, pelvic pain numerical rating scale (NRS) score of 9–10, with initial good benefits from high-dose (100mg daily) mor- phine subcutaneous pump; given the scarcity of subcu- taneous tissue, as an alternative administration route, oral controlled-release morphine plus fentanyl trans- dermal therapeutic system (TTS) was selected.