Tofthagen, Cindy S

Background: Patients have been known to use cannabinoids for treating established chemotherapy-induced peripheral neuropathy (CIPN) based on anecdotal information and retrospective reports suggesting that such might be beneficial. In response, a double-blinded, placebo-controlled, randomized, pilot clinical trial was developed to evaluate whether resultant data would support a phase III trial for testing whether a cannabidiol (CBD) cream might improve CIPN. Methods: Forty patients with established CIPN were randomized, in a double-blinded manner, to topical CBD or a placebo cream. The study product was applied for 2 weeks, followed by a crossover for 2 weeks. Neuropathy was evaluated using the European Organization of Research and Treatment of Cancer (EORTC)–CIPN20, the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool, and the Global Impression of Change instruments. Side effects were recorded by symptom diaries. Results: The EORTC-CIPN20 scores were similar in the patients receiving CBD versus the placebo. Likewise, the toxicity scores were similar in patients who received the CBD versus the placebo. Conclusions: This pilot trial did not support that the studied CBD isolate cream improved painful established CIPN. It was well tolerated overall. Clinical Trial Registration Number: NCT05388058

LBA12006 Background: Symptom burden and functional decline are prevalent, inconsistently treated, and associated with adverse health outcomes in patients with cancer. Symptom monitoring with electronic patient-reported outcome measures (ePROMs) has yielded mixed results due, in part, to care teams’ variable bandwidth and resourcing for symptom management. The collaborative care model (CCM) offers a validated means to address these issues and potentially improve clinical and health services outcomes. Capturing ePROMS through the electronic health record (EHR) for use in CCM delivery provides a potentially scalable approach to manage symptoms at the population level. Methods: E2C2 is a cluster-randomized, population-level, stepped wedge pragmatic trial that compares a bundled, EHR-facilitated, CCM-based intervention to improve control of SPPADE symptoms (Sleep interference, Pain, impaired Physical function, Anxiety, Depression, and Energy deficit/fatigue) with usual care. All patients, regardless of cancer type or stage, treated in the medical oncology clinics of a multi-state health system, were assigned to one of fifteen clusters. Control and intervention conditions monitored SPPADE symptoms with Epic EHR administered 11-point numerical rating scales (NRSs). Moderate and severe symptoms were defined as 4-6/10 and >7/10, respectively. The intervention added EHR clinician decision support; automated delivery of symptom self-management information; and options to address severe symptoms with a dedicated symptom care manager. The primary outcome was post-baseline SPPADE scores assessed using multivariate regression of six cluster-period mean SPPADE symptom scores against E2C2 exposure, fixed cluster and secular time effects. Results: From March 2019 to January 2023, 50,559 patients were assigned to E2C2 clusters and 40,295 completed at least one ePROM. At first assessment, participants’ mean age was 63.3 years; 58% were female; 26% were rural, and the prevalences of moderate or worse symptoms were fatigue 42%, impaired function 34%, sleep disturbance 34%, anxiety 27%, pain 26%, and depression 23%. The intervention significantly reduced mean composite SPPADE symptom scores, p <0.001, among all patients, as well as those with >1 moderate or worse symptom. All mean symptom scores were lower in the intervention group, with the largest effects detected among patients with fatigue -0.2 (-0.4, -0.07), anxiety -0.14 (-0.2, -0.03), and depression -0.1 (-0.2, -0.002). Conclusions: In this large cluster-randomized trial, an EHR-facilitated, bundled intervention that scaled CCM-based surveillance and management of SPPADE symptoms significantly reduced population-level symptom burden, particularly for fatigue, anxiety, and depression. This study provides real world evidence and the foundation for future national efforts aimed at controlling symptoms in patients with cancer. Clinical trial information: NCT03892967 .

LBA12004 Background: Hot flashes are among the most common adverse events impacting quality of life reported by patients receiving androgen deprivation therapy (ADT) for the treatment of prostate cancer. Oxybutynin is an effective therapy for reducing frequency and severity of hot flashes in women. Pilot information supports that this drug may also benefit men with hot flashes related to ADT. Methods: Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomized to receive either oral oxybutynin 2.5 mg twice a day, oxybutynin 5 mg twice a day, or matching placebo doses for 6 weeks. The primary endpoint was the change in patient-reported hot flash scores (determined by multiplying the number of hot flashes by the mean hot flash severity [grade 0: none, 1: mild, 2: moderate, 3: severe, and 4: very severe]) from baseline to 6 weeks, as measured by a daily hot flash diary. A total of 87 patients provided 76% power to reject the null hypothesis of no between-arm mean difference in hot flash score reduction from baseline to 6 weeks, when comparing each oxybutynin arm to the combined placebo arms. This was based on a two-sided contrast estimated from a generalized linear mixed model, α= 0.10, intraclass correlation of 0.50, population standardized mean difference of 0.50, and 10% missing data rate. Results: 88 patients were accrued between 10/28/21 and 12/02/23. Six patients cancelled before starting treatment and one was ineligible, leaving 81 analyzed patients with a median age of 68. Baseline characteristics were balanced between arms with patients reporting an average of 10.15 (SD = 5.55) hot flashes per day and an average daily hot flash score of 18.23 (SD = 13.48) at enrollment. On average, patients on the placebo arm, low dose oxybutynin arm, and high dose oxybutynin arm had reductions of 2.15, 4.77, and 6.89 hot flashes/day, respectively. Compared to placebo arm patients, high dose oxybutynin arm patients had a greater reduction in hot flashes/day (p < 0.001), as did low dose oxybutynin arm patients (p = 0.02). Daily hot flash scores for the same three protocol arms reduced by an average of 4.85, 9.94, and 13.95 points, respectively. Compared to placebo arm patients, high dose oxybutynin arm patients had a greater reduction in daily hot flash scores (p = 0.002), as did low dose oxybutynin arm patients (p = 0.07). No treatment-related grade 3+ adverse events occurred. The most commonly reported oxybutynin-related grade 2 adverse event was dry mouth. Conclusions: Oxybutynin is superior to a placebo for the management of hot flashes in men associated with androgen deprivation therapy and appears to be well tolerated. Support: UG1CA189823; https://acknowledgments.alliancefound.org . Clinical trial information: NCT04600336 .

Abstract Background: Taxane based chemotherapy (chemo) forms a critical part of breast cancer (BC) treatment in early and metastatic settings. Taxanes can cause peripheral neuropathy (CIPN)-sensory and motor, primarily of the hands and feet, resulting in quality of life decline and negaive impact on BC survival. Acral cryotherapy has shown benefit in reducing in in minimizing the incidence and severity ofcidence and severity of CIPN. However, these studies have included limited number of patients (pts) with inconclusive evidence to change US practice guidelines, have been primarily conducted in Asia, and did not include racially diverse patients. Methods: We conducted a single arm non randomized study at Mayo Clinic that included early BC pts who underwent standard of care paclitaxel or docetaxel based chemo. Pts had ECOG performance status 0-2, no sensory peripheral neuropathy at study entry and were able to give signed informed consent. Pts with metastatic BC, Raynaud's and peripheral vascular disease, cryoglobulinemia, cold intolerance, prior exposure to neurotoxic or taxane chemotherapy were excluded. Participating pts wore frozen gloves and socks (−20 to −10°C) on both hands and feet, 15 min before, during and until 15 min post taxane infusion. During chemo, grade (G) of CIPN (sensory) per CTCAE v5 was collected prior to each cycle of chemo, end of and 3 months after chemo. Schedule of events is listed in Table 1. Continuous variables were summarized using mean and standard deviation, and categorical variables were summarized with number and percentage of patients. Numeric variables were compared with t tests (paired and unpaired), and categorical variables were compared with Chi-Squared test for independent data and Mcnemar’s test for dependent data. All statistical tests were two-sided and were performed using R Statistical Software (version 4.1.2; R Foundation for Statistical Computing). Results: A total of 95 patients were included in this study. Median age is 54 years, 66.3% pts were White (W), 23.2% African American (AA), 4.2% Asian (A) and 4.2% Hispanic (H). Median BMI was 27.7. Most pts had stage I/II (75.8%), ER positive (64.9%) and HER2 negative (55.3%) BC and got adjuvant chemo (52.6%). Only 10.6% pts had diabetes, 55.3% used alcohol. Vitamin D3 use seen in 65.6%, B12 in 6.2% and folate, B12 and D3 in 6.2% pts. A total of 41 pts (44.1%) developed neuropathy at some point during chemo, of which 27 pts were W (43%), 10 pts AA (45%), 2 pts H, 1 Asian and 1 other. CIPN was G1 in 37 pts (90%). G2 CIPN was seen in 4 pts, at or after cycle 10 of weekly paclitaxel. Cold intolerance was seen in 24 pts (25%), G1 in 20 and G2 in 4 pts, all seen in cycle 1 with 1 pt withdrawal. Recovery to G0 was seen in 15 W pts at chemo end and 2 additional pts at 3 month after chemo. None of the AA pts, one H and one A pt had CIPN recovery to G0. In 4 AA pts who had G1 CIPN during chemo, G2 CIPN was noted at 3 month follow up. No Statistically significant differences in baseline characteristics and neuropathy results for W vs nonwhites (NW) were seen except Charleson score (p-value 0.023). Conclusion: Acral cryotherapy was found to be effective in reducing the incidence and severity of CIPN from taxane in our study. This is the only study with diverse racial/ethinic pt inclusion and incidence of CIPN was similar in W and NW. However, majority of G2 CIPN pts were AA and recovery to G0 CIPN was not seen in AA pts. Majority (63%) of W pts recovered to G0 at end of follow up. Analysis of objective testing of all pts is underway. Continued research into risk factors for AA pts to develop CIPN and its mitigation are warranted. XX XX Citation Format: Pooja Advani, Jinky Harvey, Ivy Vilches, Alex Hochwald, David Hodge, Amanda Arnold, Morgan Weidner, Dana Haley, Tanmayi Pai, Saranya Chumsri, Rohit Rao, Kostandinos Sideras, Cindy Tofthagen, Alvaro Moreno-Aspitia. Cryotherapy to Prevent Taxane-Induced Sensory Neuropathy of the Hands and Feet [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-10.

Background: Thirty-six states, including Florida, have legalized marijuana for medical and/or recreational use, yet how it is used and perceived by persons with cancer is not well understood. Objectives: The purpose of this study was to identify patterns of use, perceived benefits, and side effects of medical marijuana (MMJ) among cancer patients in Florida. Methods: For this descriptive, cross-sectional study, anyone residing within the state of Florida who was diagnosed or treated for a malignancy within the last five years and had used MMJ was eligible. An online survey containing questions about dosing, side effects, perceived benefits, and barriers to use was used. Descriptive statistics including frequencies, percentages, means, and standard deviations were used to analyze quantitative data. Responses to open-ended questions were coded and categorized. Results: Sleep ( n = 112), pain ( n = 96), and anxiety ( n = 82) were the most common symptoms participants used MMJ to relieve and overall felt it was highly effective. MMJ was well tolerated with a minority (10.3%) reporting any adverse effects. Cost was the most frequent barrier reported by participants (42.8%). A variety of legal, bureaucratic, and system-related barriers were described. Conclusion: Participants perceived MMJ to be helpful in alleviating cancer symptoms. They held negative perceptions of the way MMJ is implemented and integrated into their oncology treatment plan. Enhanced communication and patient/provider education on MMJ are needed to inform patient decision making.

Chemotherapy induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy for which no prevention or cure exists. Cancer and cancer treatments can adversely affect nutritional status. Nutrition may play a role in development of CIPN, yet the relationship between nutrition and CIPN is not well understood. Common laboratory values measuring various aspects of nutrition (hemoglobin/hematocrit, vitamin B12, calcium, and magnesium) may be associated with CIPN. The aim of this systematic review is to evaluate the empirical evidence surrounding the relationship between laboratory measures of nutrition and CIPN among persons with cancer who received neurotoxic chemotherapy drugs. We conducted an extensive review of the literature to identify articles that evaluated relationships between laboratory measures of nutrition and CIPN. A total of eleven articles satisfied the inclusion/exclusion criteria. Participants in the studies had breast or colorectal cancer, lymphoma or multiple myeloma and were receiving a variety of neurotoxic drugs. Hemoglobin/hematocrit, vitamin D, albumin, and magnesium were associated with CIPN. The quality of the studies ranges from fair to good. Evidence suggests that low levels of the above-mentioned tests could be associated with CIPN but additional research is needed.