The Prognosis of Lipid Reprogramming With Rosuvastatin, in Castrated Egyptian Prostate Cancer Patients
Condition: Prostate Cancer Metastatic
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 4

Summary: 
      Aim: The role of surgical castration and rosuvastatin treatment on lipid profile and lipid
      metabolism related markers was evaluated for their prognostic significance in metastatic
      prostate cancer (mPC) patients.

      Methods: A total of 70 newly diagnosed castrated mPC patients treated with castration were
      recruited and divided into two groups: Group I included 30 patients and served as control
      (statin non-users) while group II included 40 patients treated with Rosuvastatin (20 mg/day)
      for 6 months and served as statin users. Prostate specific antigen (PSA), epidermal growth
      factor receptor (EGFR), Caveolin-1, lipid profile (LDL, HDL, triglycerides and cholesterol)
      and lipid metabolism related markers (aldoketoreductase (AKR1C4), HMGCoA reductase, ABCA1,
      and SLDL RP1) were measured at baseline, after 3 and 6 months. Overall survival (OS) were
      analyzed by Kaplan-Meier and COX regression for prognostic significance.
    

Detailed description: 
      This prospective randomized controlled study was conducted at the National Cancer Institute
      (NCI), Cairo University. The study ID BB1901-30303 was approved by the Institutional Human
      Research Ethics Committee of NCI, Egypt, Number 00004025, with IRB review Number 201819019.3
      and conducted in accordance with the Declaration of Helsinki with informed consent was taken
      from all participants. The study included 70 Egyptian metastatic prostate cancer (m PC)
      patients who were treated and followed up in the NCI hospital in the period from January 2019
      till December 2020. Patients were recruited from January to June 2019, then followed-up to
      December 2020.

      Blood samples were withdrawn from all patients at baseline to monitor parameters under
      investigation. Then, all patients were subjected to surgical castration and divided in to two
      groups. Group I included 30 patients and served as control (statin non-users). Group II
      included 40 patients treated with Rosuvastatin (20 mg/day) for 6 months and served as statin
      users. Then, blood samples were withdrawn from the two groups after 3 and 6 months. Full
      demographic information and clinicopatholologic characteristics were obtained for each
      patient including; age, comorbid diseases, initial complain symptoms, family history of
      malignancy, smoking status and performance status. Also, serum level of prostate specific
      antigen (PSA) and alkaline phosphatase (ALP), Gleason score and metastasis sites were
      recorded. The treatment modality and decision making were according to NCI guidelines.

      Collected whole blood samples into k.EDTA tubes were incubated at room temperature for 15
      minutes and then centrifuged for 20 minutes at 1500 rpm. The plasma supernatant was carefully
      collected and freezed until analysis. Plasma protein concentrations of some lipid
      reprogramming and prostate cancer aggressiveness markers were measured. Kits were probed
      against human soluble low density lipoprotein receptor related protein -1 (SLDLRP-1;
      catalogue number: SL2705Hu), human ATP binding cassette transporter A-1 (ABCA-1; catalogue
      number: SL0314Hu), Human Aldoketo-reductase family 1 member C4 (AKR-1C4; catalogue number:
      SL3032Hu), human 3-hydroxy-3-methylglutaryl Co-enzyme A reductase (HMGCR; catalogue number:
      SL3030Hu), human epidermal growth factor receptor (EGFR; catalogue number: SL0665Hu) and
      human Caveolin-1 (Cav-1; catalogue number: SL0427Hu). Procedures were carried out in
      accordance with the manufacturer's instructions. The concentration of the markers in plasma
      samples was calculated by comparing the OD of the samples to the corresponding plotted
      standard curves.

      Data management and statistical analysis were performed using The Statistical Package for
      Social Sciences (SPSS) version 24. Normal distribution and variance homogeneity of data were
      assessed using the Kolmogorov-Smirnov and Levene's tests, respectively. Numerical data were
      summarized using median and interquartile range (IQR). Categorical data were summarized as
      count and percentage. Patients were stratified according to their clinicopathological factors
      and for more than two subgroups of patients, the change in measured parameters were tested
      for significance using Kruskal-Wallis test and the pairwise comparison were done using
      Mann-Whitney. The change in proteins concentration over time was tested using Friedman test
      of significance. Spearman correlation analysis was used to test all possible correlations.
      Kaplan- Meier survival analysis was used to calculate the cumulative survival rate as well as
      median levels of OS after two years of follow up. OS was calculated from date of diagnosis to
      date of death by any cause. Living patients or patients lost to follow-up were censored on
      the last known alive date. The hazardous effect of death or progression Cox proportion hazard
      Model was used to evaluate the hazardous effect of different clinicopathological and proteins
      levels on death and progression. All P-values are two-sided. P-values < 0.05 were considered
      significant.
    

Intervention name(s): Rosuvastatin 20mg; surgical castration
Intervention type(s): Drug; Procedure
Intervention description(s): Rosuvastatin 20mg/day for 6 months added to bilateral subcapsular orchiectomy; bilateral subcapsular orchiectomy
Intervention MeSH terms: Rosuvastatin Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A cohort of 70 newly diagnosed metastatic prostate cancer patients were recruited. Blood samples were withdrawn from all patients at baseline to monitor parameters under investigation. Then, all patients were subjected to surgical castration and divided in to two groups. Group I included 30 patients and served as control (statin non-users). Group II included 40 patients treated with Rosuvastatin (20 mg/day) for 6 months and served as statin users.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Prostate cancer; Rosuvastatin; Castration/Androgen deprivation; HMG-CoA Reductase; Lipid metabolism/; Survival; Aldoketoreductase 1C4; Prostate specific antigen; Alkaline phosphatase; Caveolin-1; ABCA-1; SLDL-RP1; Lipid profile; epidermal growth factor receptor