A small American study has found the plant-derived analgesic to be safe and effective.
The results of a first-in-human phase 1 study have researchers and clinicians dreaming big for patients with intractable cancer pain.
Around one in four patients with advanced cancer experience pain in their last week of life that cannot be controlled by currently available treatments. Resiniferatoxin, a plant-derived molecule, has been reported to produce analgesia in preclinical animal models without any significant adverse events.
Now, the first study investigating the effects of resiniferatoxin in human patients with intractable cancer pain has been published in NEJM Evidence. The data suggests that although all patients experienced treatment-related adverse events, a single intrathecal injection of resiniferatoxin resulted in a 38% mean reduction in self-reported worst pain intensity and a 57% median reduction in opioid consumption by day 15.
“Our data provide evidence that supports continued investigations of resiniferatoxin to improve pain management for patients with advanced cancer experiencing intractable pain, especially when opioids fail or are poorly tolerated,” the researchers concluded.
“Although it requires an anaesthetic for drug administration, the appeal of this intervention is that it has the potential to improve pain control with a single durable treatment, while potentially decreasing the need for other drugs or interventions.”
US researchers recruited 19 palliative patients with severe refractory cancer pain (nine women, median age 57 years) as part of the pilot and phase 1 dose escalation study. All patients received a single dose of resiniferatoxin, ranging from 3μg to 100μg via spinal catheter and were followed for up to 188 days.
All 19 patients experienced at least one adverse event, with 213 treatment-emergent events (37 of which were classified as serious adverse events) being reported during the study period. Fifteen of the 19 patients were deemed to have an adverse event that was “possibly or probably” related to the resiniferatoxin treatment.
Common adverse events included anaemia (reported by 47% of patients), fever (42%), urinary retention (37%), abnormal liver enzymes (37%), decreased thermal sensitivity (26%) and nausea or vomiting (21%). The researchers said the decreased thermal sensitivity was expected in body regions exposed to resiniferatoxin.
Nine deaths occurred during the study period. None were considered to be related to the treatment.
Daily pain ratings (i.e., a rating of the worst pain patients had experienced over the last 24 hours on a scale of 0 to 10, with higher numbers indicating more pain) and opioid consumption were also measured as secondary outcomes.
Related
The average “worst” pain intensity for the 15 patients in the phase 1 study decreased from 8.4 prior to treatment to 5.8 at day 15 (a 38% reduction), while the median daily morphine intake decreased from 306 equivalents at baseline to 209 equivalents. Twenty per cent of patients reported a ≥50% reduction in their worst pain intensity, and 40% of patients reported a ≥50% reduction in their daily oral morphine equivalent intake.
“The primary strength of this approach lies in its selectivity and durability. Unlike opioids, which act broadly and are associated with sedation, constipation and respiratory depression, resiniferatoxin offers localised, lasting analgesia without substantial systemic side effects, other than the expected burning pain with drug administration that was mitigated by administering the treatment under anaesthesia,” wrote Associate Professors Krishna Shah and Bilal Dar – both anaesthesiologists from Baylor College of Medicine in the US – in an accompanying editorial.
“Achieving durable pain control through a single administration may reduce reliance on escalating doses of systemic analgesics, which potentially has a significant advantage in the palliative setting. Preservation of cognition and mobility, as observed here, is particularly relevant to quality-of-life goals in advanced cancer care.”
Resiniferatoxin targets the transient receptor potential vanilloid (TRPV1) ion channel – also called the capsaicin receptor – which is responsible for the detection and regulation of body temperature. The TRPV1 receptors located in primary afferent sensory neurons respond to noxious heat stimuli and play a key role in the human nociceptive system. Many painkillers target the TRPV1 receptor as a way of reducing nociceptive signalling.
Palliative care specialist and Palliative Care Australia Board chair Dr Peter Allcroft said the management of cancer related pain was becoming increasingly complex.
“Opioids have a known array of side effects, and there is concern over long term use for people living with cancer as a chronic disease,” hesaid.
“This novel, new agent for helping to provide pain relief at the end of life for someone living with advanced cancer and severe pain is worthy of further investigation.
“The study was only a small open label pilot study. Further clinical research is welcomed to explore the possibilities of this novel analgesic agent.”
