Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT-ROC feasibility study

Abstract

Background: Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT.Methods: For this multicentre, double-blind, parallel-group, randomized, placebo-controlled feasibility trial, adults with OAC (including Siewert I-II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival.Results: A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26⋅7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low-density lipoprotein cholesterol levels by 3 months (adjusted mean difference −0⋅83 (95 per cent c.i. −1⋅4 to −0⋅22) mmol/l; P = 0⋅009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow-up. Adverse events were similar between the groups. Quality-of-life data were complete for 98⋅3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non-randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise.Conclusion: This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com).

Efficacy and safety profile of statins in patients with cancer: a systematic review of randomised controlled trials

“…Among 1008 articles identified from the literature search, 15 full-text articles were assessed for eligibility, of which eleven were ultimately eligible for inclusion ( Fig. 1) [21][22][23][24][25][26][27][28][29][30][31]. The four excluded articles met all inclusion criteria except for the outcomes of interest, instead focusing on surrogate outcomes [32][33][34][35].…”

“…Of the eleven RCTs, six originated from East Asia [23,[26][27][28][29]31]. Four studies were performed in Europe [21,22,24,30] and one in Egypt [25]. All studies were conducted in hospital-based settings.…”

“…The largest trial included 846 patients (LUNGSTAR) across 91 UK centres [24]. The gastro-intestinal tract and accessory digestive organs were the primary site examined in seven trials, including cancers of the gastro-oesophageal junction/stomach [27,30], oesophagus/gastro-oesophageal junction [21], pancreas [26], liver [22,31] and colorectum [26]. The remaining studies separately recruited patients with small cell lung cancer [24], non-small cell lung cancer [23,29] and brain metastases (with various primary tumour sites) [25].…”

“…The remaining studies separately recruited patients with small cell lung cancer [24], non-small cell lung cancer [23,29] and brain metastases (with various primary tumour sites) [25]. Eight of the trials explicitly excluded prior/current statin users [21,22,[24][25][26][28][29][30], and no trials reported the proportion of prior/current users among the randomised population. The intervention arm in seven studies was simvastatin [21,23,[25][26][27][28][29] and in four studies was pravastatin [22,24,30,31].…”

“…One trial of pravastatin in hepatocellular carcinoma administered statins for a mean of 16.5 months [31]. Concomitant chemo/radiotherapy was administered in all but one trial [21].…”