A Randomized Controlled Open-Label Pilot Study of Simvastatin Addition to Whole-Brain Radiation Therapy in Patients With Brain Metastases

Abstract

Statins have been reported to have a potential radiosensitizing effect that has not been evaluated in clinical trials. The aim of this study was to evaluate the efficacy and safety of simvastatin in addition to whole-brain radiation therapy (WBRT) in patients with brain metastases (BM). A prospective randomized, controlled, open-label pilot study was conducted on 50 Egyptian patients with BM who were randomly assigned to receive 30-Gy WBRT (control group: 25 patients) or 30 Gy WBRT + simvastatin 80 mg/day for the WBRT period (simvastatin group: 25 patients). The primary outcome was radiological response at 4 weeks after WBRT. Secondary outcomes were 1-year progression-free survival (PFS), 1-year overall survival (OS), and health-related quality of life (HRQL) that was assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and its brain module (BN-20), at baseline, after WBRT, and 4 weeks after WBRT. The addition of simvastatin was tolerated. Twenty-one patients were not evaluated for radiological response because of death (n = 16), noncompliance to follow-up (n = 4), and clinical deterioration (n = 1). Response rates were 60% and 78.6% (p = 0.427), 1-year PFS rates were 5.2% and 17.7% (p = 0.392), and 1-year OS rates were 12% and 8% (p = 0.880) for the control group and simvastatin group, respectively. Nonsignificant differences were found between the two arms regarding HRQL scales. The addition of simvastatin 80 mg/day did not improve the clinical outcomes of patients with BM receiving WBRT.

Simvastatin-Romidepsin Combination Kills Bladder Cancer Cells Synergistically

“…Preclinical studies demonstrated that it induces apoptosis and inhibits tumor growth in a variety of cancer cells [12-14, 57, 58]. Combinations of simvastatin and an anticancer agent or radiotherapy have not been effective in patients with advanced cancer (Table 4) [59][60][61][62][63][64]; however, given simvastatin's wide-ranging physiological properties, there is still a need to evaluate the anticancer effect of simvastatin in combination with other types of anticancer agents.…”

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.…”

“…In total, 2165 participants were recruited across all trials. Four studies were conducted at a single site and included between 30 and 106 participants [25,[29][30][31]. 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]. 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.…”