Intrathecal resiniferatoxin may decrease cancer pain intensity and reduce opioid consumption: NEJM

A new study published in The New England Journal of Medicine Evidence showed that for patients with unmanageable cancer pain, single dose of intrathecal resiniferatoxin (RTX), an opioid-sparing analgesic may be effective.

Even with thorough medical care, a significant portion of patients with advanced cancer experience refractory pain. A powerful member of the capsaicin-containing medication family, resiniferatoxin selectively and permanently kills the neurons (or their axons) that convey chronic pain. In a number of animal species, intrathecal injection of RTX has shown a high degree of safety, specificity, and effectiveness in alleviating severe pain.

In this study, Andrew Mannes and colleagues assessed resiniferatoxin (RTX), a nonopioid analgesic that selectively blocks nociceptive activity sent by a subset of dorsal root ganglion neurons. RTX is a strong agonist of the transient receptor potential vanilloid 1 (TRPV1) ion channel.

This is an interim analysis of a first-in-human, open-label, Phase 1 research in which 19 patients with lower extremity and/or abdominal refractory cancer pain received a single intrathecal RTX dosage. Safety was the main result. A numerical rating scale assessing the "worst pain" during a 24-hour period was used to evaluate effectiveness during the research, which produced secondary outcomes. On this scale, 0 represents "no pain" and 10 represents "worst pain imaginable." The amount of opioids needed to manage pain was assessed in morphine equivalents.

A total of 213 treatment-emergent adverse events (AEs) were recorded in 19 patients treated over a period of 188 days following RTX injection, with 14 patients experiencing 37 significant AEs. Between 11 and 140 days following treatment, 9 fatalities happened on average 70 days later.

The progression of advanced cancer is associated with many of these occurrences, including death. All 19 patients experienced at least one adverse event. The dermatomes of three individuals (grades I and II) exposed to RTX lost their sensitivity to heat.

3 of the 7 patients had grade III urine retention, which lasted longer than 24 hours. 5 individuals experienced AEs (grades I and II) associated with a brief elevation in the electrocardiogram's QT interval that went down in a day.

An unstageable decubitus ulcer was the sole grade IV adverse event. At posttreatment day 15, RTX was linked to a 38% reduction in "worst" pain intensity (pretreatment 8.4±0.4 vs. posttreatment 5.2±0.6) and a 57% reduction in opiate intake. Overall, intrathecal RTX, taken as a single dosage, acts as an opioid-free analgesic for cancer patients suffering from intractable pain. 

Source:

Mannes, A. J., Heiss, J. D., Berger, A., Alewine, C. C., Butman, J. A., Hughes, M. S., Rabbee, N., Hayes, C., Williams, T. S., Sapio, M. R., & Iadarola, M. J. (2025). Treatment of intractable cancer pain with resiniferatoxin - an interim study. NEJM Evidence, 4(6), EVIDoa2400423. https://doi.org/10.1056/EVIDoa2400423