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Effects of high-intensity exercise training on physical fitness, quality of life and treatment outcomes after oesophagectomy for cancer of the gastro-oesophageal junction: PRESET pilot study.

ABSTRACT: BACKGROUND:Treatment for cancer of the gastro-oesophageal junction (GOJ) can result in considerable and persistent impairment of physical fitness and health-related quality of life (HRQoL). This controlled follow-up study investigated the feasibility and safety of postoperative exercise training. METHODS:Patients with stage I-III GOJ cancer were allocated to 12?weeks of postoperative concurrent aerobic and resistance training (exercise group) or usual care (control group). Changes in cardiorespiratory fitness, muscle strength and HRQoL were evaluated. Adherence to adjuvant chemotherapy, hospitalizations and 1-year overall survival were recorded to assess safety. RESULTS:Some 49 patients were studied. The exercise group attended a mean of 69 per cent of all prescribed sessions. After exercise, muscle strength and cardiorespiratory fitness were increased and returned to pretreatment levels. At 1-year follow-up, the exercise group had improved HRQoL (+13·5 points, 95 per cent c.i. 2·2 to 24·9), with no change in the control group (+3·7 points, -5·9 to 13·4), but there was no difference between the groups at this time point (+9·8 points, -5·1 to 24·8). Exercise was safe, with no differences in patients receiving adjuvant chemotherapy (14 of 16 versus 16 of 19; relative risk (RR) 1·04, 95 per cent c.i. 0·74 to 1·44), relative dose intensity of adjuvant chemotherapy (mean 57 versus 63 per cent; P =?0·479), hospitalization (7 of 19 versus 6 of 23; RR 1·41, 0·57 to 3·49) or 1-year overall survival (80 versus 79 per cent; P =?0·839) for exercise and usual care respectively. CONCLUSION:Exercise in the postoperative period is safe and may have the potential to improve physical fitness in patients with GOJ cancer. No differences in prognostic endpoints or HRQoL were observed. Registration number: NCT02722785 ( https://www.clinicaltrials.gov).

SUBMITTER: Simonsen C

PROVIDER: S-EPMC7528530 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Effects of high-intensity exercise training on physical fitness, quality of life and treatment outcomes after oesophagectomy for cancer of the gastro-oesophageal junction: PRESET pilot study.

Simonsen C C Thorsen-Streit S S Sundberg A A Djurhuus S S SS Mortensen C E CE Qvortrup C C Pedersen B K BK Svendsen L B LB de Heer P P Christensen J F JF

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<h4>Background</h4>Treatment for cancer of the gastro-oesophageal junction (GOJ) can result in considerable and persistent impairment of physical fitness and health-related quality of life (HRQoL). This controlled follow-up study investigated the feasibility and safety of postoperative exercise training.<h4>Methods</h4>Patients with stage I-III GOJ cancer were allocated to 12 weeks of postoperative concurrent aerobic and resistance training (exercise group) or usual care (control group). Changes ...[more]

PMID: 32856785

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Project description:BACKGROUND:TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. METHODS:Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. RESULTS:In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40?-?82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1?-?5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6?-?4.9]), median time to progression (TTP) was 2.9 months (CI [1.4?-?4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. CONCLUSIONS:This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response. TRIAL REGISTRATION:EU-CTR 2009-012097-12 2009-09-03.

Project description:BackgroundCardiorespiratory fitness and fatness (notably central obesity) are mediating factors of the metabolic syndrome (MetS) and consequent cardiovascular disease (CVD)/mortality risk. The fitness-fatness index (FFI) combines these factors and has been reported to be a better indicator of CVD and all-cause mortality risk, beyond the capacity of either fitness or fatness alone.ObjectiveThis study sought to investigate the effects of different exercise intensities on FFI in adults with MetS.MethodsThis was a sub-study of the 'Exercise in the prevention of Metabolic Syndrome' (EX-MET) multicentre trial. Ninety-nine adults diagnosed with MetS according to the International Diabetes Federation criteria were randomized to one of the following 16-week exercise interventions: i) moderate-intensity continuous training (MICT) at 60-70% HRpeak for 30 min/session (n = 34, 150 min/week); ii) 4 × 4 min bouts of high-intensity interval training at 85-95% HRpeak, interspersed with 3-min active recovery at 50-70% HRpeak (n = 34, 38 min/session, 114 min/week); and iii) 1 × 4 min bout of HIIT at 85-95% HRpeak (n = 31, 17 min/session, 51 min/week). Cardiorespiratory fitness (peak oxygen uptake, V̇O2peak) was determined via indirect calorimetry during maximal exercise testing and fatness was the ratio of waist circumference-to-height (WtHR). FFI was calculated as V̇O2peak in metabolic equivalents (METs) divided by WtHR. A clinically meaningful response to the exercise intervention was taken as a 1 FFI unit increase.ResultsSeventy-seven participants completed pre and post testing to determine FFI. While there was no significant between group difference (p = 0.30), there was a small group x time interaction effect on FFI [F(2, 73) = 1.226; η2 = 0.01], with numerically greater improvements following HIIT (4HIIT, + 16%; 1HIIT, + 11%) relative to MICT (+ 7%). There was a greater proportion of participants who had a clinically meaningful change in FFI following high-volume HIIT (60%, 15/25) and low-volume HIIT (65%, 17/26) compared to MICT (38%, 10/26), but with no significant between-group difference (p = 0.12). A similar trend was found when a sub-analysis comparing the FFI between those with type 2 diabetes (MICT, 33%, 3/9; high-volume HIIT, 64%, 7/11; and low-volume HIIT, 58%, 7/12) and without type 2 diabetes (MICT, 41%, 7/17; high-volume HIIT, 57%, 8/14; low-volume HIIT, 71%, 10/14).ConclusionAlthough there were no statistically significant differences detected between groups, this study suggests that the response to changes in FFI in adults with MetS may be affected by exercise intensity, when numerical differences between exercise groups are considered. Further research is warranted. Trial registration number and date of registration: ClinicalTrials.gov NCT01676870; 31/08/2012.

Project description:BackgroundAddition of trastuzumab to first-line chemotherapy improves overall survival in patients with HER2-positive metastatic gastric cancer. We assessed the safety and activity of pembrolizumab in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic oesophagogastric (gastric, oesophageal, or gastroesophageal junction) cancer.MethodsThis study was an investigator-initiated, open-label, non-randomised, single-arm, single centre, phase 2 trial in patients aged 18 years or older with HER2-positive metastatic oesophagogastric cancer. Eligible patients had measurable or evaluable non-measurable disease, Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and left ventricular ejection fraction of at least 53%. Patients were eligible to receive an initial induction cycle of 200 mg flat dose of intravenous pembrolizumab and 8 mg/kg loading dose of intravenous trastuzumab. For subsequent cycles, patients received 130 mg/m2 of intravenous oxaliplatin or 80 mg/m2 of cisplatin on day 1, 850 mg/m2 of oral capecitabine twice a day for 2 weeks followed by 1 week off (or intravenous 5-fluorouracil, 800 mg/m2 per day on days 1-5), and a 200 mg flat dose of intravenous pembrolizumab, and 6 mg/kg of trastuzumab, administered on day 1 of each 3-week cycle. The primary endpoint was 6-month progression-free survival, defined as the proportion of patients alive and free of progression at 6 months, assessed in patients who received at least one dose of trastuzumab and pembrolizumab. The regimen would be considered worthy of further investigation if 26 or more of 37 patients were progression-free at 6 months. This trial is registered with ClinicalTrials.gov, NCT02954536, and is ongoing, but closed to enrolment.FindingsBetween Nov 11, 2016, and Jan 23, 2019, 37 patients were enrolled. At the time of data cutoff on Aug 6, 2019, median follow-up among survivors was 13·0 months (IQR 11·7-23·5). The primary endpoint was achieved; 26 (70%; 95% CI 54-83) of 37 patients were progression-free at 6 months. The most common treatment-related adverse event of any grade was neuropathy, which was reported in 36 (97%) of 37 patients. The most common grade 3 or 4 adverse events were lymphocytopenia (seven [19%] patients with grade 3 and two [5%] with grade 4), grade 3 decreased electrolytes (six [16%] patients), and grade 3 anaemia (four [11%] patients). Serious adverse events occurred in two patients patients (both grade 3 nephritis leading to treatment discontinuation). Four patients discontinued pembrolizumab because of immune-related adverse events. There were no treatment-related deaths.InterpretationPembrolizumab can be safely combined with trastuzumab and chemotherapy and has promising activity in HER2-positive metastatic oesophagogastric cancer. A randomised phase 3 clinical trial assessing the efficacy and safety of pembrolizumab versus placebo in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic oesophagogastric cancer is underway.FundingMerck & Co.

Project description:The human epidermal receptor-2 (HER-2) is amplified in up to 25% of patients with gastroesophageal adenocarcinomas. Although the presence of this amplification does not appear to confer a poor prognosis, it provides a valuable novel therapeutic target for this group of patients. Trastuzumab is a fully humanized monoclonal antibody directed at HER-2 which binds the external domain of the receptor and exerts its action via a combination of antibody-dependent cytotoxicity, reduced shedding of the extracellular domain, inhibition of dimerization and possibly receptor downregulation. The ToGA trial was an international multicentre randomized phase III study which evaluated the addition of trastuzumab to a cisplatin plus fluoropyrimidine chemotherapy doublet in 594 patients with HER-2-positive advanced gastric or oesophagogastric junction adenocarcinoma. The combination of the antibody with chemotherapy significantly improved response rate, median progression-free survival and median overall survival without additional toxicity or adversely affecting quality of life. Accordingly, trastuzumab plus chemotherapy is now a standard first-line treatment option for patients with advanced HER-2-positive gastroesophageal cancer. Unfortunately, many patients with HER-2-positive cancer exhibit primary resistance to trastuzumab and the remainder will acquire resistance to the antibody; therefore, urgent investigation into novel agents which may circumvent resistance mechanisms is warranted. Small molecule inhibitors of HER-2, which commonly also target other members of the HER family of receptors, such as EGFR and HER-3, are currently undergoing evaluation in gastroesophageal cancer as first-line alternatives to trastuzumab and second-line salvage treatments for trastuzumab-resistant disease. Extrapolating the successful use of trastuzumab in the advanced disease setting, clinical trials are underway to assess the role of this antibody in the perioperative and adjuvant settings, where it is hoped that it will have a meaningful impact upon the currently poor survival rates.

Dataset Information

Effects of high-intensity exercise training on physical fitness, quality of life and treatment outcomes after oesophagectomy for cancer of the gastro-oesophageal junction: PRESET pilot study.

Publications

Effects of high-intensity exercise training on physical fitness, quality of life and treatment outcomes after oesophagectomy for cancer of the gastro-oesophageal junction: PRESET pilot study.

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