High Protein Oral Nutritional Supplements Enable the Majority of Cancer Patients to Meet Protein Intake Recommendations during Systemic Anti-Cancer Treatment:A Randomised Controlled Parallel-Group Study

ESPEN guidelines recommend a minimum protein intake of 1.0 g/kg body weight (BW) per day to maintain or restore lean body mass in patients with cancer. During anti-cancer treatment, optimal protein intake is difficult to achieve. We investigated whether a high-protein, low-volume oral nutritional supplement (ONS) supports patients in meeting recommendations. A multi-centre, randomised, controlled, open-label, parallel-group study was carried out in nine hospitals (five countries) between January 2019 and July 2021 in colorectal and lung cancer patients undergoing first-line systemic treatment with chemo(radio-) or immunotherapy. Subjects were randomised (2:1) to receive Fortimel Compact Protein® or standard care. Protein intake was assessed with a 3-day food diary (primary outcome). BW was a secondary outcome. Due to challenges in recruitment, the study was terminated prematurely with 42 patients randomised (intervention group (IG) 28; control group (CG) 14). At T1 and T2, protein intake was statistically significantly higher in the IG compared to the CG (1.40 vs. 1.07 g/kg/day at T1, p = 0.008; 1.32 vs. 0.94 g/kg/day at T2, p = 0.002). At baseline, only 65% (IG) and 45% (CG) of patients met ESPEN minimum protein intake recommendations. However, at T1 and T2 in the IG, a higher proportion of patients met recommendations than in the CG (88% vs. 55% and 40%). No statistically significant difference between study groups was observed for BW. Mean compliance to the ONS was 73.4%. A high-protein, low-volume ONS consumed twice daily enables the majority of patients to reach minimal ESPEN protein recommendations.</p

Switch-maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma (NVALT19):an investigator-initiated, randomised, open-label, phase 2 trial

Background Almost all patients with malignant mesothelioma eventually have disease progression after first-line therapy. Previous studies have investigated maintenance therapy, but none has shown a great effect. We aimed to assess the efficacy and safety of switch-maintenance gemcitabine in patients with malignant mesothelioma without disease progression after first-line chemotherapy. Methods We did a randomised, open-label, phase 2 trial in 18 hospitals in the Netherlands (NVALT19). We recruited patients aged older than 18 years with unresectable malignant mesothelioma with no evidence of disease progression after at least four cycles of first-line chemotherapy (with platinum and pemetrexed), who had a WHO performance status of 0-2, adequate organ function, and measurable or evaluable disease. Exclusion criteria were active uncontrolled infection or severe cardiac dysfunction, serious disabling conditions, symptomatic CNS metastases, radiotherapy within 2 weeks before enrolment, and concomitant use of any other drugs under investigation. Patients were randomly assigned (1:1), using the minimisation method, to maintenance intravenous gemcitabine (1250 mg/m(2) on days 1 and 8, in cycles of 21 days) plus supportive care, or to best supportive care alone, until disease progression, unacceptable toxicity, serious intercurrent illness, patient request for discontinuation, or need for any other anticancer agent, except for palliative radiotherapy. A CT scan of the thorax or abdomen (or both) and pulmonary function tests were done at baseline and repeated every 6 weeks. The primary outcome was progression-free survival in the intention-to-treat population. Safety was analysed in all participants who received one or more doses of the study drug or had at least one visit for supportive care. Recruitment is now closed; treatment and follow-up are ongoing. This study is registered with the Netherlands Trial Registry, NTR4132/NL3847. Findings Between March 20, 2014, and Feb 27, 2019, 130 patients were enrolled and randomly assigned to gemcitabine plus supportive care (65 patients [50%]) or supportive care alone (65 patients [50%]). No patients were lost to follow-up; median follow-up was 36.5 months (95% CI 34.2 to not reached), and one patient in the supportive care group withdrew consent. Progression-free survival was significantly longer in the gemcitabine group (median 6.2 months [95% CI 4.6-8.7]) than in the supportive care group (3.2 months [2.8-4.1]; hazard ratio [HR] 0.48 [95% CI 0.33-0.71]; p=0.0002). The benefit was confirmed by masked independent central review (HR 0.49 [0.33-0.72]; p=0.0002). Grade 3-4 adverse events occurred in 33 ( 52%) of 64 patients in the gemcitabine group and in ten (16%) of 62 patients in the supportive care group. The most frequent adverse events were anaemia, neutropenia, fatigue or asthenia, pain, and infection in the gemcitabine group, and pain, infection, and cough or dyspnoea in the supportive care group. One patient (2%) in the gemcitabine group died, due to a treatment-related infection. Interpretation Switch-maintenance gemcitabine, after first-line chemotherapy, significantly prolonged progression-free survival compared with best supportive care alone, among patients with malignant mesothelioma. This study confirms the activity of gemcitabine in treating malignant mesothelioma

Multimodal prehabilitation in patients with non-small cell lung cancer undergoing anatomical resection: protocol of a non-randomised feasibility study

Abstract Background The preoperative period can be used to enhance a patient’s functional capacity with multimodal prehabilitation and consequently improve and fasten postoperative recovery. Especially, non-small cell lung cancer (NSCLC) surgical patients may benefit from this intervention, since the affected and resected organ is an essential part of the cardiorespiratory fitness. Drafting a prehabilitation programme is challenging, since many disciplines are involved, and time between diagnosis of NSCLC and surgery is limited. We designed a multimodal prehabilitation programme prior to NSCLC surgery and aimed to conduct a study to assess feasibility and indicative evidence of efficacy of this programme. Publication of this protocol may help other healthcare facilities to implement such a programme. Methods The multimodal prehabilitation programme consists of an exercise programme, nutritional support, psychological support, smoking cessation, patient empowerment and respiratory optimisation. In two Dutch teaching hospitals, 40 adult patients with proven or suspected NSCLC will be included. In a non-randomised fashion, 20 patients follow the multimodal prehabilitation programme, and 20 will be assessed in the control group, according to patient preference. Assessments will take place at four time points: baseline, the week before surgery, 6 weeks postoperatively and 3 months postoperatively. Feasibility and indicative evidence of efficacy of the prehabilitation programme will be assessed as primary outcomes. Discussion Since the time between diagnosis of NSCLC and surgery is limited, it is a challenge to implement a prehabilitation programme. This study will assess whether this is feasible, and evidence of efficacy can be found. The non-randomised fashion of the study might result in a selection and confounding bias. However, the control group may help putting the results of the prehabilitation group in perspective. By publishing this protocol, we aim to facilitate others to evaluate and implement a multimodal prehabilitation programme for surgical NSCLC patients. Trial registration The current study is registered as NL8080 in the Netherlands Trial Register on the 10th of October 2019, https://www.trialregister.nl/trial/8080 . Secondary identifiers: CCMO (Central Committee on Research Involving Human Subjects) number NL70578.015.19, reference number of the Medical Ethical Review Committee of Máxima MC W19.045