Landiolol, an ultra-short acting beta-1 blocker, for preventing postoperative lung cancer recurrence: study protocol for a phase III, multicenter randomized trial with two parallel groups of patients

Abstract

BackgroundRecurrence of cancer after curative surgery is a major problem after most cancer treatments. Increased sympathetic activity during the perioperative period could promote cancer cell invasion to blood vessels and angiogenesis, resulting in cancer metastasis. Recent studies showed that use of beta blockers can be associated with the prolonged survival of patients with cancer. The objective of this study is to evaluate the preventive effects of landiolol hydrochloride, which is an ultra-short-acting beta-1-selective blocker that has been developed in Japan, on reducing recurrence of cancer after curative surgery for patients with lung cancer.MethodsThe present study is a phase III, multicenter, randomized trial with two parallel groups of patients with lung cancer, comparing surgery alone and surgery with landiolol administration for three days during the perioperative period. A total of 400 patients will be enrolled from 12 Japanese institutions. The primary endpoint is two-year relapse-free survival and overall survival after curative surgery for lung cancer. The secondary endpoints are additional treatment after recurrence of cancer, safety events, and the incidence of postoperative complications.DiscussionThe principal question addressed in this trial is whether landiolol can reduce recurrence of cancer after curative surgery for lung cancer.Trial registrationJapan Registry of Clinical Trials, jRCT2011180004. Registered 17 January 2019.

The updated landscape of tumor microenvironment and drug repurposing

“… 195 The selective β1 blocker landiolol reduces lung cancer recurrence after operation. 196 Additionally, β-blockers positively affect cancer patients by reducing their intrusive thoughts. 197 Overall, the effects of β-blockers on TME and the whole organism indicate their potential application in future cancer treatments.…”

Beta-blocker and survival in patients with lung cancer: A meta-analysis

“…In a retrospective study with 77 patients of stage IIIa NSCLC treated with neoadjuvant chemoradiation and subsequent surgery, BB users were associated with a trend of improved OS at 1 year compared with the non-users in univariate analysis (p = 0.08) [ 39 ]. Another study with 57 lung cancer patients showed that perioperative intravenous administration of an ultra-short acting SBB landiolol prolonged relapse-free survival in these patients [ 40 ], and a phase III RCT has been started accordingly [ 41 ]. Results of future prospective studies and RCTs are expected to provide more reliable evidence regarding the association between BB use and OS in patients with lung cancer, preferably according in different histopathological type.…”

Biobehavioral Pathways and Cancer Progression: Insights for Improving Well-Being and Cancer Outcomes

“…There are an increasing number of larger ongoing β-blocker RCTs aimed at assessing clinical cancer outcomes. 222 However, an obstacle to success in these studies is the limitation in recruitment due to competition with other traditional pharma-supported oncology trials that typically prohibit additional treatment with another agent such as propranolol. 214 , 223 As such, several attempts to test the impact of β-blockade in the context of cancer treatment have been terminated prematurely due to poor accrual (NCT02596867, NCT01857817, NCT03323710) or funding obstacles (NCT01988831).…”