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Abstract: Background. Advance care planning (ACP) supports individuals to define, discuss, and record goals and preferences for future medical treatment and care. Despite being internationally recommended, randomised clinical trials of ACP in patients with advanced cancer are scarce. Methods and findings. To test the implementation of ACP in patients with advanced cancer, we conducted a cluster-randomised trial in 23 hospitals across Belgium, Denmark, Italy, Netherlands, Slovenia, and United Kingdom in 2015–2018. Patients with advanced lung (stage III/IV) or colorectal (stage IV) cancer, WHO performance status 0–3, and at least 3 months life expectancy were eligible. The ACTION Respecting Choices ACP intervention as offered to patients in the intervention arm included scripted ACP conversations between patients, family members, and certified facilitators; standardised leaflets; and standardised advance directives. Control patients received care as usual. Main outcome measures were quality of life (operationalised as European Organisation for Research and Treatment of Cancer [EORTC] emotional functioning) and symptoms. Secondary outcomes were coping, patient satisfaction, shared decision-making, patient involvement in decision-making, inclusion of advance directives (ADs) in hospital files, and use of hospital care. In all, 1,117 patients were included (442 intervention; 675 control), and 809 (72%) completed the 12-week questionnaire. Patients’ age ranged from 18 to 91 years, with a mean of 66; 39% were female. The mean number of ACP conversations per patient was 1.3. Fidelity was 86%. Sixteen percent of patients found ACP conversations distressing. Mean change in patients’ quality of life did not differ between intervention and control groups (T-score −1.8 versus −0.8, p = 0.59), nor did changes in symptoms, coping, patient satisfaction, and shared decision-making. Specialist palliative care (37% versus 27%, p = 0.002) and AD inclusion in hospital files (10% versus 3%, p < 0.001) were more likely in the intervention group. A key limitation of the study is that recruitment rates were lower in intervention than in control hospitals. Conclusions. Our results show that quality of life effects were not different between patients who had ACP conversations and those who received usual care. The increased use of specialist palliative care and AD inclusion in hospital files of intervention patients is meaningful and requires further study. Our findings suggest that alternative approaches to support patient-centred end-of-life care in this population are needed.
Keywords: advanced care planning, medical treatment, advanced cancer, palliative care
Published in DiRROS: 14.12.2020; Views: 1346; Downloads: 1287
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Abstract: Background: Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods: To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings: Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37,298 (93%) of 40,070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28.0% vs 31.4%; RR 0.86, 95% CI 0.82-0.89; p<0.0001). 10-year breast cancer mortality was similarly reduced (18.9% vs 21.3%; RR 0.87, 95% CI 0.83-0.92; p<0.0001), as was all-cause mortality (22.1% vs 24.8%; RR 0.87, 95% CI 0.83-0.91; p<0.0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4.1% vs 4.6%; RR 0.88, 95% CI 0.78-0.99; p=0.034). Recurrence reductions were similar in the seven trials (n=10,004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24.0% vs 28.3%; RR 0.83, 95% CI 0.76-0.91; p<0.0001), in the six trials (n=11,028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28.1% vs 31.3%; RR 0.87, 95% CI 0.80-0.94; p=0.0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30.4% vs 35.0%; RR 0.82, 95% CI 0.74-0.90; p<0.0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0.0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation: Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.
Keywords: breast neoplasms, women, drug therapy, clinical protocols, meta-analysis, breast cancer, chemotherapy, treatment schedule, randomized trials
Published in DiRROS: 22.10.2020; Views: 1312; Downloads: 1106
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Abstract: Background. Treatment of non-small cell lung cancer (NSCLC) improved substantially in the last decades. Novel targeted and immune-oncologic drugs were introduced into routine treatment. Despite accelerated development and subsequent drug registrations by the European Medicinal Agency (EMA), novel drugs for NSCLC are poorly accessible in Central and Eastern European (CEE) countries. Material and Methods. The Central European Cooperative Oncology Group conducted a survey among experts from 10 CEE countries to provide an overview on the availability of novel drugs for NSCLC and time from registration to reimbursement decision in their countries. Results. Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors were reimbursed and available in all countries, for other registered therapies - even for ALK inhibitors and checkpoint inhibitors in first-line - there were apparent gaps in availability and/or reimbursement. There was a trend for better availability of drugs with longer time from EMA marketing authorization. Substantial differences in access to novel drugs among CEE countries were observed. In general, the availability of drugs is not in accordance with the Magnitude of Clinical Benefit Scale (MCBS), as defined by the European Society for Medical Oncology (ESMO). Time spans between drug registrations and national decisions on reimbursement vary greatly, from less than 3 months in one country to more than 1 year in the majority of countries. Conclusion. The access to novel drugs for NSCLC in CEE countries is suboptimal. To enable access to the most effective compounds within the shortest possible time, reimbursement decisions should be faster and ESMO MCBS should be incorporated into decision making.
Keywords: non-small cell lung cancer, treatment, novel drugs, Central Europe, Southeastern Europe
Published in DiRROS: 24.07.2020; Views: 1837; Downloads: 1073
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