Simvastatin Effect in Combination With Neoadjuvant Chemotherapy to Clinical Response and Tumor-Free Margin in Locally Advanced Breast Cancer

• Status: Completed
• Trial end date: 2019-09-05
• Target enrollment: 0
• Participant gender: Female

Summary

Introduction: Neoadjuvant chemotherapy (NACT) has been the standard therapy for treating patients with locally advanced breast cancer (LABC). Doxorubicin-based regimen showed a clinical response for 70-80%. However, the cardiotoxicity from it was not tolerable. Simvastatin acts synergistically with doxorubicin against MCF-7 cells, through downregulation of the cell cycle or induction of apoptosis. Also, it alleviates doxorubicin cardiotoxicity by attenuating ER stress and activating the Akt pathway. Hmgcris a new pathway mediating doxorubicin-induced cell death, and cholesterol control drugs combined with doxorubicin could enhance efficacy and reduce side effects. This study is conducted to see the combination simvastatin and CAF would increase the NACT response and surgical margin of LABC patients.

Methods: This study was a double-blind, randomized placebo-controlled trial, conducted in dr. Cipto Mangunkusumo General Hospital and Koja General Hospital. A total of 70 LABC patients were assessed for eligibility. Patients received either a combination of CAF-Simvastatin (40 mg/day) or CAF-Placebo. The biopsy was taken pre-NACT to make the histopathological diagnosis and examine the expression of HMG-CoA Reductase (Hmgcr) and P-glycoprotein (P-gp). Patients were evaluated for the clinical response after 3 cycles. If the response was positive, patients will proceed to surgery. Then, the post-operative specimen will be reviewed for the pathological response. However, if it was a negative response, patients will be given 2nd line NACT.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Indonesia University
• Treatments: Simvastatin

Criteria

Inclusion Criteria:

• LABC IIIA-IIIC TNM / AJCC 2018 with histopathological examination.

• Patients are planned to get NACT

• Performance status of Eastern Cooperative Oncology Group (ECOG) 0-2.

• LABC patients who have not received surgery, radiation or systemic therapy and previous statin therapy.

• Normal kidney organ function (serum creatinine ≤ 1.5 upper limit normal).

• Normal liver organ function (ALT ≤ 2 times the normal limit, or total bilirubin level ≤ 1.5 times the normal upper limit)

• Heart function (E / F)> 55%

• Willing to participate in this study by signing an informed consent

Exclusion Criteria:

• LABC patients are both residual and recurrent.

• Allergy to tattoo ink

• Allergy to statins

• Patients are pregnant or breastfeeding