Treatment of Intractable Cancer Pain with Resiniferatoxin — An Interim Study

BACKGROUND: A substantial number of patients with advanced cancer suffer from refractory pain despite comprehensive medical management. In this article, we evaluate a nonopioid analgesic, resiniferatoxin (RTX), a potent agonist of the transient receptor potential vanilloid 1 (TRPV1) ion channel, which selectively interrupts nociceptive activity transmitted by a subpopulation of dorsal root ganglion neurons. METHODS: In this interim analysis of a first-in-human, open-label, Phase 1 study, 19 patients with refractory cancer pain localized to the abdomen and/or lower extremities received one dose of intrathecal RTX. The primary outcome was safety. Secondary outcomes were efficacy assessed over the course of the study using a numerical rating scale measuring the "worst pain" over a 24-hour period. This is a 0 to 10 scale where 0 is "no pain" and 10 is the "worst pain imaginable." Opioid consumption was measured as morphine equivalents used to control pain. RESULTS: Over 188 days after RTX injection, a total of 213 treatment-emergent adverse events (AEs) were reported among 19 patients treated, including 37 serious adverse events in 14 patients. Nine deaths occurred an average of 70 days after treatment (range from 11 to 140 days). Many of these events, including death, are consistent with the course of advanced cancer. At least one AE occurred in all 19 patients. Three patients experienced loss of heat sensitivity in the dermatomes exposed to RTX (grades I and II). Seven patients experienced urinary retention lasting more than 24 hours (three were grade III). Five patients had AEs related to a transient increase in the electrocardiographic QT interval that resolved within 24 hours (grades I and II). The only grade IV AE was an unstageable decubitus ulcer. RTX was associated with decreased "worst" pain intensity by 38% (pretreatment 8.4±0.4 vs. posttreatment 5.2±0.6) and reduced opioid consumption by 57% measured at posttreatment day 15. CONCLUSIONS: Intrathecal RTX is a single-administration, opioid-sparing analgesic in patients with intractable cancer pain. There were expected and unexpected AEs of various grades with an encouraging initial impact on pain. (Funded by the Intramural Research Program of the National Institutes of Health Clinical Center and others; ClinicalTrials.gov number, NCT00804154).