Abstract 469P
Background
Refractory cancer pain does not respond adequately to standard pain management treatment. In vitro and in vivo studies have shown that HSE confers central and peripheral analgesic effects. This study explored the safety, tolerability, and efficacy of adding HSE to standard opioid analgesia in patients with refractory cancer pain.
Methods
Patients with an average NRS score of 3-6 who reported unsatisfactory pain control after 1-2 weeks of opioid treatment were enrolled into a phase I dose-finding study using a standard 3+3 design. In combination with a stable dose of standard opioid analgesia given over 7 days, subjects received five escalating dose levels of HSE: 8.0 g BID, 12.0 g BID, 16.0 g BID, 16.0 g TID, or 24.0 g TID. Primary objectives were safety, tolerability, and recommended phase II dose (RP2D).
Results
Fifteen subjects were enrolled (3 at each dose level[CRM1] ). Median age was 58 (range 29-73) years; 8 pts (53.3%) were female. Primary cancer sites included: colorectal (n=10); stomach (n=4); and pancreatic (n=1). Metastatic sites included: lymphatics (n=10); liver (n=6); bone (n=5); peritoneum (n=4); lung (n=3); and other (n=3). The median average [CRM2] NRS score at baseline was 4 (IQR: 3.00-4.75). All subjects were evaluated for dose-limiting toxicity (DLT); none occurred within the 7-day treatment period and no maximum tolerated dose was reached. A mixed-effects model used to analyze NRS scores showed that they tended to decrease as the number of days increased. Using a linear regression equation to analyze the relationship between NRS scores and number of days for each dose level showed the largest decrease in the 24.0g TID group in which the NRS score decreased by an average of 0.26 points for every additional day. The RP2D was identified as 24.0 g TID. Eight subjects experienced grade 1-2 treatment-related adverse events including anorexia (n=3), nausea (n=2), vomiting (n=2), and constipation (n=1).
Conclusions
HSE combined with standard opioid analgesia was well tolerated and showed preliminary adjuvant analgesic activity in patients with refractory cancer pain.
Clinical trial identification
NCT05561023.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Shanghai Hongguobao Biotechnology Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.