Abstract P4-04-02: Evaluation of Dronabinol to Decrease Opioid Use for Cancer- Induced Bone Pain
Authors: Segar Jennifer , Farr Kiah , Junak Mary , Roe Denise , Ehsani Sima , Jiralerspong Sao , Mohab Ibrahim , Vanderah Todd , Chalasani Pavani 
Published: March 2023

Abstract
Purpose Bone metastases (BM) from breast cancer cause significant complications including pain, hypercalcemia, spinal cord compression, and pathologic fractures, collectively referred to as skeletal related events (SREs). Of all SREs, bone pain impacts the quality of life (QOL) most significantly. Cancer- induced bone pain (CIBP) is difficult to treat with limited treatment options and requires a multimodal approach. Management of CIBP is primarily by opioids which have notable side effects like sedation, constipation, and concern for addiction. In addition, pre-clinical evidence suggests that opioids accelerate bone loss and increase risk of fractures. There is an unmet need for novel analgesic therapy interventions to optimize QOL for patients with BM from metastatic breast cancer. Preclinical studies have shown that the endogenous cannabinoid (CB) system is involved in pain modulation, bone regulation, immunity, and restraint of cancer pathogenesis. CB2 receptor activation has been shown to inhibit proinflammatory cytokines/chemokines in pre-clinical models. Treatment with selective CB2 agonist in mice with BM led to significant antinociception, decreased cancer-induced bone degradation, and reduced side effects of morphine. In addition to alleviating pain, CB2 agonists were shown to enhance bone growth/strength in these mice. Based on this pre-clinical data, we hypothesized that the addition of a CB2 agonist will improve pain symptoms and decrease opioid requirement in patients with bone metastases from breast cancer. We proceeded to conduct a pilot study by repurposing a clinically approved CB2/CB1 agonist, dronabinol. Methods We conducted a prospective, single site study among patients with BM from breast cancer at our center (NCT03661892). Patients had to have been on opioids for CIBP for at least 4 weeks and not using marijuana or CBD products. Patients were treated with 10mg dronabinol BID for 8 weeks. Our primary objective was to determine the proportion who decrease their opioid use by ≥ 20%. The null hypothesis value was 5% of women would have a 20% decrease. With 14 participants, we could detect an increase from 5% to 29% (n=4) with 80% statistical power using a one-sided alpha level of 0.05. Participants completed Brief Pain Inventory and the European Organization for Research and Treatment of Cancer quality of life questionnaires pre and post treatment. Results Twenty participants consented with 14 patients completing the study and evaluable for primary analysis. No patients received any palliative radiation therapy or other therapies for bone pain within 3 months prior to enrollment to this study. Four patients decreased their opioid use by ≥ 20% meeting the primary objective. Patients reported significant improvement in pain severity, interference scores, quality of life and insomnia based on the questionnaires. There were no grade 4 side effects and only 1 patient had grade 3 adverse event (dizziness) related to study drug. Of the 14 patients who completed the study, 9 desired to continue dronabinol therapy after completion. Conclusion Our pilot study shows that the addition of dronabinol resulted in decreased opioid requirements for CIBP in patients with metastatic breast cancer. Patient-reported outcomes also demonstrated improved pain and QOL with the addition of dronabinol. While we did not see any significant AEs tolerability may be of concern due to CB1 psychoactive effects. Our results are promising and warrant further investigation into evaluating CB2 agonists for improved pain control from CIBP and to decrease opioid use.
Citation Format: Jennifer Segar, Kiah Farr, Mary Junak, Denise Roe, Sima Ehsani, Sao Jiralerspong, Ibrahim Mohab, Todd Vanderah, Pavani Chalasani. Evaluation of Dronabinol to Decrease Opioid Use for Cancer- Induced Bone Pain [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-04-02.