The Prognosis of Lipid Reprogramming With Rosuvastatin, in Castrated Egyptian Prostate Cancer Patients

The Prognosis of Lipid Reprogramming With the HMG-CoA Reductase Inhibitor, Rosuvastatin, in Castrated Egyptian Prostate Cancer Patients

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer Metastatic
• Intervention / Treatment: Procedure: surgical castration; Drug: Rosuvastatin 20mg

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Blood samples were withdrawn from all patients at baseline to monitor parameters under investigation.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 Then, blood samples were withdrawn from the two groups after 3 and 6 months.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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 112796
    • National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Naïve newly diagnosed with metastatic prostate cancer
• Age ≥ 50 years.
• No psychological or geographical barriers for regular follow up of the patients.

Exclusion Criteria:

• Age < 50 years.
• psychological or geographical barriers for regular follow up of the patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control/statin non-users; newly diagnosed metastatic prostate cancer patients who underwent surgical castration in the form of bilateral subcapsular orchiectomy.	Procedure: surgical castration; bilateral subcapsular orchiectomy
Experimental: Interventional/statin users; newly diagnosed metastatic prostate cancer patients who underwent surgical castration in the form of bilateral subcapsular orchiectomy and administered rosuvastatin 20 mg/day for 6 months	Drug: Rosuvastatin 20mg; Rosuvastatin 20mg/day for 6 months added to bilateral subcapsular orchiectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid profile	effect of adding rosuvastatin to surgical castration on the lipid profile (LDL, triglycerides, cholesterol, HDL) in mg/dl	6 months
Aggressiveness parameters	effect of adding rosuvastatin to surgical castration on the PSA in ng/ml	6 months
Aggressiveness parameters	effect of adding rosuvastatin to surgical castration on the ALP in IU/L	6 months
Aggressiveness parameters	effect of adding rosuvastatin to surgical castration on the EGFR in ng/ml	6 months
Aggressiveness parameters	effect of adding rosuvastatin to surgical castration on the Caveolin-1 in pg/ml	6 months
Lipid metabolism parameters	effect of adding rosuvastatin to surgical castration on HMG-CoA reductase in ng/ml	6 months
Lipid metabolism parameters	effect of adding rosuvastatin to surgical castration on SLDLRP1 in pg/ml	6 months
Lipid metabolism parameters	effect of adding rosuvastatin to surgical castration on AKR1C4 ng/L	6 months
Lipid metabolism parameters	effect of adding rosuvastatin to surgical castration on ABCA-1 in pg/ml	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
short-term clinical outcome	disease progression/regression	18 months
short-term clinical outcome	overall survival	18 months

Collaborators and Investigators

• Sponsor: National Cancer Institute, Egypt

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2019
• Primary Completion (Actual): December 30, 2020
• Study Completion (Actual): December 30, 2020

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (Actual): March 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 2, 2021
• Last Update Submitted That Met QC Criteria: February 25, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Survival; Prostate cancer; Lipid profile; Prostate specific antigen; Rosuvastatin; Alkaline phosphatase; epidermal growth factor receptor; Castration/Androgen deprivation; HMG-CoA Reductase; Lipid metabolism/; Aldoketoreductase 1C4; Caveolin-1; ABCA-1; SLDL-RP1
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: CB1901-30303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: requests for individual participant data should be directed to riham.karkeet@nci.cu.edu.eg, and shall not be limited to specific institutes/researchers
• IPD Sharing Time Frame: for 2 years after publication
• IPD Sharing Access Criteria: requests for participant data should be directed to riham.karkeet@nci.cu.edu.eg, and shall not be limited to specific institutes/researchers
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes