Oral Cannabis Extract for Secondary Prevention of Chemotherapy-Induced Nausea and Vomiting: Final Results of a Randomized, Placebo-Controlled, Phase II/III Trial.

PURPOSE: The aim of this randomized, placebo-controlled, two-stage, phase II/III trial was to determine the efficacy of an oral cannabis extract in adults with refractory nausea and/or vomiting during moderately or highly emetogenic, intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Here, we report results of the prespecified combined analysis including the initial phase II and subsequent phase III components. PATIENTS AND METHODS: Study treatment consisted of oral capsules containing either tetrahydrocannabinol 2.5 mg plus cannabidiol 2.5 mg capsules (THC:CBD) or matching placebo, taken three times a day from days -1 to 5, in addition to guideline-consistent antiemetics. The primary measure of effect was the difference in the proportions of participants with no vomiting or retching and no use of rescue medications (a complete response) during hours 0-120 after the first cycle of chemotherapy on study (cycle A). RESULTS: We recruited 147 evaluable of a planned 250 participants from 2016 to 2022. Background antiemetic prophylaxis included a corticosteroid and 5-hydroxytryptamine antagonist in 97%, a neurokinin-1 antagonist in 80%, and olanzapine in 10%. THC:CBD compared with placebo improved the complete response rate from 8% to 24% (absolute difference 16%, 95% CI, 4 to 28, P = .01), with similar effects for absence of significant nausea, use of rescue medications, daily vomits, and the nausea scale on the Functional Living Index-Emesis quality-of-life questionnaire. More frequent bothersome adverse events of special interest included sedation (18% v 7%), dizziness (10% v 0%), and transient anxiety (4% v 1%). There were no serious adverse events attributed to THC:CBD. CONCLUSION: THC:CBD is an effective adjunct for chemotherapy-induced nausea and vomiting despite standard antiemetic prophylaxis, but was associated with additional adverse events. Drug availability, cultural attitudes, legal status, and preferences may affect implementation. Future analyses will evaluate the cost-effectiveness of THC:CBD.

Telehealth cognitive behaviour therapy for the management of sleep disturbance in women with early breast cancer receiving chemotherapy: a feasibility study.

PURPOSE: Sleep quality commonly deteriorates in people receiving chemotherapy for breast cancer (BC). We aimed to determine feasibility and acceptability of telehealth-delivered cognitive behaviour therapy for insomnia (CBT-I) in people with early BC receiving (neo)adjuvant chemotherapy. METHODS: Multi-centre, single arm, phase 2 feasibility trial. People with stage I-III BC received 4 sessions of telehealth CBT-I over 8 weeks, during chemotherapy. Participants completed Pittsburgh Sleep Quality Index (PSQI) and other Patient Reported Outcome Measures (PROMs) at baseline, post-program (week 9) and post-chemotherapy (week 24); and an Acceptability Questionnaire at week 9. Primary endpoint was proportion completing 4 sessions of telehealth CBT-I. RESULTS: In total, 41 participants were recruited: mean age 51 years (range 31-73). All 4 CBT-I sessions were completed by 35 (85%) participants. Acceptability of the program was high and 71% reported 'the program was useful'. There was no significant difference in the number of poor sleepers (PSQI score ≥ 5) at baseline 29/40 (73%) and week 24 17/25 (68%); or in the mean PSQI score at baseline (7.43, SD 4.06) and week 24 (7.48, SD 4.41). From baseline to week 24, 7/25 (28%) participants had a ≥ 3 point improvement in sleep quality on PSQI, and 5/25 (20%) had a ≥ 3 point deterioration. There was no significant difference in mean PROM scores. CONCLUSION: It is feasible to deliver telehealth CBT-I to people with early BC receiving chemotherapy. Contrary to literature predictions, sleep quality did not deteriorate. Telehealth CBT-I has a potential role in preventing and managing sleep disturbance during chemotherapy. Australian New Zealand Clinical Trials Registry (ANZCTR) registration number: ACTRN12620001379909 and date 22/12/2020.

Baduanjin Mind-Body Exercise for Cancer-Related Fatigue: Protocol for a Remotely Delivered Randomized Wait-List Controlled Feasibility Study.

BACKGROUND: People living with a cancer diagnosis often experience cancer-related fatigue (CRF). Between 9% and 45% of people report CRF as moderate to severe, negatively impacting their quality-of-life (QOL). The evidence-base for managing CRF recommends exercise-related therapies over pharmaceutical interventions. One such exercise-like therapy is Baduanjin mind-body exercise (MBE), which has additional benefits. A remotely delivered program may further benefit people with CRF. The primary objective of this pilot will test study feasibility of a remotely delivered Baduanjin MBE exercise program for people living with CRF. METHODS: This is a randomized wait-list controlled pilot study and will take place in Sydney, Australia. Subject to informed consent, 40 adults with moderate CRF levels and receiving or previously received adjuvant chemotherapy, will undertake a home-based 8-week Baduanjin MBE program supported by online resources and instructors. The primary feasibility outcomes are recruitment, enrollment, retention, and adherence rates; and safety as measured by tolerance and adverse-event frequency. Clinical outcomes (eg, changes in CRF, QOL, and participant perceptions) are assessed at pre-intervention, week 1, week 4, week 8, and post-intervention. Analyses follows the Intent-to-Treat (all participants as per randomization) and per-protocol (participants adhering to the protocol). Missing data will be imputed from previous data entries and regression models may be tested to predict missing outcomes. DISCUSSION: To our knowledge, this is the first study evaluating the feasibility and effects of Baduanjin MBE on CRF using a remote delivery method. These feasibility data will inform a fully powered future trial investigating evidence of effect on CRF and QOL.Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR 12623000177651).Ringgold ID: 651498 Chinese Medicine Centre.

Cancer Care Team's Management of Clinical Alerts Generated by Electronically Collected Patient Reported Outcomes: We Could Do Better.

Electronically administered patient-reported outcome measures (ePROMs) are effective digital health tools for informing clinicians about cancer patients' symptoms and facilitating timely patient-centred care. This paper describes the delivery of healthcare activities supported by the PROMPT-Care model, including ePROMs generated clinical alerts, cancer care team (CCT) response to alerts, and patients' perceptions of the CCT response and ePROMs system. This mixed-methods study includes cancer patients from four cancer therapy centres in New South Wales, Australia. Quantitative and qualitative data were collected regarding clinical alert activity, CCT response, and patient perceptions of the CCT responses and ePROMs system. Qualitative data were thematically analysed. Of the 328 participants whose care was informed by the digital health tool, 70.8% (n = 233) generated at least one alert during the trial period, with 877 alerts generated in total. Although 43.7% (n = 383) were actioned by the CCT, at least 80% of participants found follow-up CCT phone calls beneficial, with multiple benefits confirmed in interviews. The cancer care delivery arm of the PROMPT-Care trial involving clinical alerts to the CCT was positively perceived by most participants, resulting in a diverse range of benefits. However, further work is required, informed by implementation science, to improve the percentage of actioned clinical alerts.

Web-Based Patient-Reported Outcome Measures for Personalized Treatment and Care (PROMPT-Care): Multicenter Pragmatic Nonrandomized Trial.

BACKGROUND: Despite the acceptability and efficacy of e-patient-reported outcome (ePRO) systems, implementation in routine clinical care remains challenging. OBJECTIVE: This pragmatic trial implemented the PROMPT-Care (Patient Reported Outcome Measures for Personalized Treatment and Care) web-based system into existing clinical workflows and evaluated its effectiveness among a diverse population of patients with cancer. METHODS: Adult patients with solid tumors receiving active treatment or follow-up care in four cancer centers were enrolled. The PROMPT-Care intervention supported patient management through (1) monthly off-site electronic PRO physical symptom and psychosocial well-being assessments, (2) automated electronic clinical alerts notifying the care team of unresolved clinical issues following two consecutive assessments, and (3) tailored online patient self-management resources. Propensity score matching was used to match controls with intervention patients in a 4:1 ratio for patient age, sex, and treatment status. The primary outcome was a reduction in emergency department presentations. Secondary outcomes were time spent on chemotherapy and the number of allied health service referrals. RESULTS: From April 2016 to October 2018, 328 patients from four public hospitals received the intervention. Matched controls (n=1312) comprised the general population of patients with cancer, seen at the participating hospitals during the study period. Emergency department visits were significantly reduced by 33% (P=.02) among patients receiving the intervention compared with patients in the matched controls. No significant associations were found in allied health referrals or time to end of chemotherapy. At baseline, the most common patient reported outcomes (above-threshold) were fatigue (39%), tiredness (38.4%), worry (32.9%), general wellbeing (32.9%), and sleep (24.1%), aligning with the most frequently accessed self-management domain pages of physical well-being (36%) and emotional well-being (23%). The majority of clinical feedback reports were reviewed by nursing staff (729/893, 82%), largely in response to the automated clinical alerts (n=877). CONCLUSIONS: Algorithm-supported web-based systems utilizing patient reported outcomes in clinical practice reduced emergency department presentations among a diverse population of patients with cancer. This study also highlighted the importance of (1) automated triggers for reviewing above-threshold results in patient reports, rather than passive manual review of patient records; (2) the instrumental role nurses play in managing alerts; and (3) providing patients with resources to support guided self-management, where appropriate. Together, these factors will inform the integration of web-based PRO systems into future models of routine cancer care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000615482; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370633. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12885-018-4729-3.

Older adults' preferred and perceived roles in decision-making about palliative chemotherapy, decision priorities and information preferences.

AIM: Patients with cancer have varied preferences for involvement in decision-making. We sought older adults' preferred and perceived roles in decision-making about palliative chemotherapy; priorities; and information received and desired. METHODS: Patients ≥65y who had made a decision about palliative chemotherapy with an oncologist completed a written questionnaire. Preferred and perceived decision-making roles were assessed by the Control Preferences Scale. Wilcoxon rank-sum tests evaluated associations with preferred role. Factors important in decision-making were rated and ranked, and receipt of, and desire for information was described. RESULTS: Characteristics of the 179 respondents: median age 74y, male (64%), having chemotherapy (83%), vulnerable (Vulnerable Elders Survey-13 score ≥ 3) (52%). Preferred decision-making roles (n = 173) were active in 39%, collaborative in 27%, and passive in 35%. Perceived decision-making roles (n = 172) were active in 42%, collaborative in 22%, and passive in 36% and matched the preferred role for 63% of patients. Associated with preference for an active role: being single/widowed (p = .004, OR = 1.49), having declined chemotherapy (p = .02, OR = 2.00). Ranked most important (n = 159) were "doing everything possible" (30%), "my doctor's recommendation" (26%), "my quality of life" (20%), and "living longer" (15%). A minority expected chemotherapy to cure their cancer (14%). Most had discussed expectations of cure (70%), side effects (88%) and benefits (82%) of chemotherapy. Fewer had received quantitative prognostic information (49%) than desired this information (67%). CONCLUSION: Older adults exhibited a range of preferences for involvement in decision-making about palliative chemotherapy. Oncologists should seek patients' decision-making preferences, priorities, and information needs when discussing palliative chemotherapy.

Risk of emergency hospitalisation and survival outcomes following adjuvant chemotherapy for early breast cancer in New South Wales, Australia.

OBJECTIVE: To examine risk of emergency hospital admission and survival following adjuvant chemotherapy for early breast cancer. METHODS: Linked data from New South Wales population-based and clinical cancer registries (2008-2012), hospital admissions, official death records and pharmaceutical benefit claims. Women aged ≥18 years receiving adjuvant chemotherapy for early-stage operable breast cancer in NSW public hospitals were included. Odds ratios (OR) for emergency hospitalisation within 6 months following chemotherapy initiation were estimated using logistic regression and survival using Kaplan-Meier and Cox proportional hazards methods. RESULTS: A total of 3,950 women were included and 30.6% were hospitalised. The most common principal diagnosis at admission was neutropenia (30.8%). Women receiving docetaxel/carboplatin/trastuzumab (TCH) and docetaxel/cyclophosphamide (TC) were the most frequently hospitalised. After adjustment for demographic and clinical factors, the increased risk of hospitalisation for TCH and TC remained compared with doxorubicin/cyclophosphamide 3-weekly (OR 1.71, 95% confidence interval [CI] 1.24-2.37 and OR 1.47, 95% CI 1.17-1.85 respectively). Five-year overall survival was similar for women who were (92.2%, 95% CI 90.7-93.8) and were not hospitalised (93.1%, 95% CI 92.1-94.1). CONCLUSION: Emergency hospitalisations following chemotherapy for early breast cancer were relatively common, especially following docetaxel-containing protocols. Further examination of reasons for admission is needed to inform actions to improve patient safety.

Development and Feasibility Testing of PROMPT-Care, an eHealth System for Collection and Use of Patient-Reported Outcome Measures for Personalized Treatment and Care: A Study Protocol.

BACKGROUND: Patient-reported outcome (PRO) measures have been used widely to screen for depression, anxiety, and symptoms in cancer patients. Computer-based applications that collect patients' responses and transfer them to the treating health professional in real time have the potential to improve patient well-being and cancer outcomes. OBJECTIVE: This study will test the feasibility and acceptability of a newly developed eHealth system which facilitates PRO data capture from cancer patients, data linkage and retrieval to support clinical decisions and patient self-management, and data retrieval to support ongoing evaluation and innovative research. METHODS: The eHealth system is being developed in consultation with 3 overarching content-specific expert advisory groups convened for this project: the clinical advisory group, technical advisory group, and evaluation advisory group. The following work has already been completed during this phase of the study: the Patient-Reported Outcome Measures for Personalized Treatment and Care (PROMPT-Care) eHealth system was developed, patient-reported outcomes were selected (distress, symptoms, unmet needs), algorithms to inform intervention thresholds for clinical and self-management were determined, clinician PRO feedback summary and longitudinal reports were designed, and patient self-management resources were collated. PROsaiq, a custom information technology system, will transfer PRO data in real time into the hospital-based oncology information system to support clinical decision making. The PROMPT-Care system feasibility and acceptability will be assessed through patients completing PROMPT-Care assessments, participating in face-to-face cognitive interviews, and completing evaluation surveys and telephone interviews and oncology staff participating in telephone interviews. RESULTS: Over the course of 3 months, the system will be pilot-tested with up to 50 patients receiving treatment or follow-up care and 6 oncology staff at 2 hospitals in New South Wales, Australia. Data will be collected to determine the accuracy and completeness of data transfer procedures, extent of missing data from participants' assessments, acceptability of the eHealth system and usefulness of the self-management resources (via patient evaluation surveys and interviews), and acceptability and perceived usefulness of real-time PRO reporting (via oncology staff interviews) at the completion of the pilot phase. CONCLUSIONS: This research investigates implementation of evidence into real world clinical practice through development of an efficient and user-friendly eHealth system. This study of feasibility and acceptability of the newly developed eHealth system will inform the next stage of larger scale testing and future implementation of the system as part of routine care. CLINICALTRIAL: Australian New Zealand Clinical Trials Registry ACTRN1261500135294; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369299&isReview=true (Archived by WebCite at http://www.webcitation.org/6lzylG5A0).

Geriatric assessment of older patients with cancer in Australia--a multicentre audit.

OBJECTIVE: The aim of this study is to determine the frequency of geriatric assessment in patients aged over 70 years in Australian medical oncology clinics. MATERIAL AND METHODS: This was a multicentre audit in two parts: a retrospective file review of initial consultations with an oncologist and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Data was collected at six oncology centres in Victoria, NSW and Canberra from October 2009 to March 2010. RESULTS: Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age was 76 years (range 70-95). The geriatric assessment (GA) domains most frequently assessed during an initial consultation were the presence of comorbidities (92%), social situation-living alone or with someone (80%), social supports (63%), any mention of at least one Activity of Daily Living (ADL) (50%) and performance status (49%). Less frequently assessed were any Instrumental Activity of Daily Living (IADL) (26%), presence of a geriatric syndrome (24%), polypharmacy (29%) and creatinine clearance (11%). Only one patient had all components of ADLs and IADLs assessed. During MDMs all the geriatric domains were comparatively less frequently assessed. No patients had all ADL and IADL components discussed formally in an MDM. CONCLUSION: This is the first multicentre audit that reveals the low rates of GA in Australian medical oncology practice and describes the GA domains considered important by oncology clinicians.

Relative dose intensity in early stage breast cancer chemotherapy: A retrospective analysis of incidence, risk factors and outcomes at a south-west Sydney cancer clinic.

AIM: In early stage breast cancer chemotherapy relative dose intensity (RDI) of <85% leads to poorer outcomes. This study assesses what proportion of such patients at a south-west Sydney cancer clinic received optimal RDI and the reasons and risk factors contributing to RDI reduction, as well as comparing survival outcomes. METHODS: A retrospective analysis of 308 patients treated with adjuvant chemotherapy for early stage breast cancer at the Macarthur Cancer Centre was undertaken, with an overall RDI calculated for each patient. The study analysed reasons for reductions in RDI as well as predictive factors for reduced RDI and overall and disease-free survival. RESULTS: Mean RDI was 92%. Of the participants, 17% had an RDI less than 85%, 55% received 100% RDI. Hematological toxicity, infection and patient choice were the most common reasons for RDI reduction. Body surface area capping (BSA) was the most common cause of initial dose reduction. Obesity, increasing body mass index and age ≥65 years were risk factors for RDI reduction. Disease-free and overall survival were reduced with RDI < 50%; overall survival decreased when RDI < 65%. CONCLUSION: Most patients attained the RDI benchmark; however dose intensity reducing events occurred frequently. Despite contrary recommendations in the literature, BSA capping and dose reduction due to patient choice were common. Implementation of focused patient and physician education strategies may improve these results, as could measures directed as supporting those at risk (i.e. elderly or obese).

Factors delaying chemotherapy for breast cancer in four urban and rural oncology units.

BACKGROUND: Delays in commencing adjuvant chemotherapy for early breast cancer beyond 12 weeks are associated with increased mortality. The aim of this study was to identify factors delaying chemotherapy in an inner metropolitan, outer metropolitan, small rural and large rural cancer centre in New South Wales, Australia. METHODS: We retrospectively reviewed 400 consecutive patients that received adjuvant chemotherapy for stages I-III breast cancer. We evaluated factors affecting time from primary and definitive surgery until commencing chemotherapy. RESULTS: The primary factor associated with chemotherapy delays was the geographic location of the cancer centre. The median time from primary surgery to chemotherapy was longer for the large rural centre (median 58 days), compared with the outer metropolitan (45 days), small rural (39 days) and inner metropolitan centre (33 days). Treatment delays in the large rural centre were associated with higher rates of multiple operations (43% versus 31% elsewhere), mainly because of more staged axillary dissections (34% versus 19%), and longer time from definitive surgery to oncology assessment. CONCLUSION: Patients in the large rural centre, who are served by fly-in medical oncology services, are more likely to experience delays in receiving adjuvant chemotherapy for early breast cancer. Strategies to reduce delays include use of intraoperative frozen section analysis, multidisciplinary meetings, improving efficiency in pathology reporting and employment of a breast cancer care coordinator and an on-site medical oncologist.

A pilot study of preoperative and postoperative chemotherapy in patients with operable gastric cancer: Australasian Gastrointestinal Trials Group Study 9601.

BACKGROUND: With poor cure rates in gastric cancer using surgery alone, the safety, efficacy and feasibility of preoperative and postoperative chemotherapy was investigated. METHODS: Patients with advanced but operable gastric or cardio-oesophageal adenocarcinoma were staged using endoscopy, computed tomography scan and laparoscopy. If considered potentially resectable, they received chemotherapy (epirubicin, cisplatin and 5-fluorouracil) for 9 weeks before and after surgery. RESULTS: Of 59 participants entered, two were found to have metastatic disease and were excluded from the analysis. Of the participants, 10 were women and 47 men; their median age was 58 years (range 27-83 years) and median performance status 0 (range 0-1). Two of the 57 participants commencing chemotherapy did not undergo surgery (one sudden death, one new liver metastases). Grade 3 and 4 preoperative and postoperative toxicity rates were, respectively, neutropenia 22 and 18%, emesis 12 and 14% and other non-haematological toxicity <10 and <10%. Of the 55 who underwent surgery, 40 had apparently curative resections (clear or positive microscopic margins), 2 died after surgery (anastomotic leak, sepsis) and 16 had postoperative complications. Of these, 27 participants commenced postoperative chemotherapy and 21 completed it. Median progression-free survival and overall survival were 19.6 and 22 months, respectively. CONCLUSION: Epirubicin, cisplatin and protracted venous infusion of 5-fluorouracil chemotherapy was well-tolerated in the preoperative setting and did not appear to increase complication rates of surgery for advanced and operable stomach cancer. These findings demonstrate the feasibility of this strategy in the Australasian clinical setting and are in keeping with the results of a recently reported randomized trial, which demonstrated a significant survival advantage using this chemotherapy regimen.