Editor's Note: Refractory cancer pain often responds poorly to standard pain management strategies. Both in vitro and in vivo studies have shown that hawthorn standardized extract (HSE) possesses central and peripheral analgesic effects. At the 2024 European Society for Medical Oncology Asia Congress (ESMO Asia 2024), Dr. Rongbo Lin’s team from Fujian Cancer Hospital presented findings from a phase I clinical trial exploring the safety, tolerability, and efficacy of HSE combined with standard opioid therapy for the treatment of refractory cancer pain (Abstract #469P). Oncology Frontier interviewed Dr. Liyu Su, a member of Dr. Lin’s team, to discuss the study in detail. Below is a summary of the conversation for our readers.________________________________________
Study Overview
This study employed a standard 3+3 dose-escalation design, enrolling patients with a Numerical Rating Scale (NRS) pain score of 3–6 who reported unsatisfactory pain control despite 1–2 weeks of opioid therapy. On top of stable doses of standard opioid analgesics administered for 7 consecutive days, participants received escalating doses of HSE: 8.0 g, 12.0 g, or 16.0 g twice daily (BID), or 16.0 g or 24.0 g three times daily (TID). The primary endpoints were safety, tolerability, and the recommended phase II dose (RP2D).
A total of 15 participants were enrolled, with three patients in each dose cohort. The median age of participants was 58 years (range: 29–73), and 8 (53.3%) were female. Primary tumor sites included the colorectal region (n=10), stomach (n=4), and pancreas (n=1), with metastases affecting lymph nodes (n=10), liver (n=6), bone (n=5), peritoneum (n=4), lungs (n=3), and other locations (n=3).
At baseline, the median NRS pain score was 4 (interquartile range: 3.00–4.75). All participants underwent dose-limiting toxicity (DLT) evaluation, with no DLTs or maximum tolerated doses (MTDs) observed during the 7-day treatment period.
A mixed-effects model analyzing NRS scores over time showed a downward trend in pain levels. Linear regression analysis revealed the greatest reduction in pain scores in the 24.0 g TID group, with an average daily decrease of 0.26 points. Based on these results, the RP2D was determined to be 24.0 g TID.
Regarding safety, 8 participants experienced grade 1–2 treatment-related adverse events (TRAEs), including anorexia (n=3), nausea (n=2), vomiting (n=2), and constipation (n=1).
In conclusion, HSE combined with standard opioid therapy demonstrated good tolerability and preliminary auxiliary analgesic effects in patients with refractory cancer pain.
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Insights from the Researchers
On the background of the study:
Dr. Su explained, “Refractory cancer pain patients often respond poorly to standard opioid therapy, resulting in generally low satisfaction with pain management. Our team has been dedicated to exploring new, effective treatments to improve outcomes for these patients.”
“By chance, we noticed a patient undergoing stable opioid therapy who experienced poor pain control initially but later reported significantly better pain management. During follow-up, we discovered that the patient had been consuming hawthorn extract. Upon reviewing the literature, we found evidence suggesting that hawthorn extract possesses central and peripheral analgesic effects in both basic and preclinical studies. This prompted us to initiate a phase I clinical trial to investigate the safety and efficacy of combining hawthorn extract with standard opioid therapy in refractory cancer pain management.”
On key findings:
“The study involved five dose cohorts, with the highest dose being 24 g TID. At this dose, we observed a statistically significant reduction in pain scores, with an average daily decrease of 0.26 points. Importantly, no DLTs were observed, even at the highest dose level during the 7–14 day observation period, and the MTD was not reached.
“While the results are promising, the current regimen requires patients to take 90 tablets (24 g) daily, which is impractical for clinical use. Administering large quantities of tablets every few hours or during meals creates significant challenges for patient compliance.”
On future research directions:
“Our future research will focus on optimizing extraction methods, improving pharmacokinetics, and understanding the active components and mechanisms of action of hawthorn extract. These efforts aim to enhance the practicality and clinical utility of this therapy. Ultimately, our goal is to bring this treatment into clinical practice and deliver meaningful analgesic benefits to patients with refractory cancer pain.”
