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临床试验/NCT04151355
NCT04151355Unknown不适用

The Effect of Atorvastatin on The Prevention of 5-fluorouracil-induced Mucositis in Colorectal Cancer Patients

Ain Shams University1 个研究点 分布在 1 个国家目标入组 100 人开始时间: 2019年10月1日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
不适用
入组人数
100
试验地点
1
主要终点
incidence of mucositis

研究概览

简要总结

5-Fuorouracil (5-Fu) remains one of the most effective and most commonly used drugs to treat colorectal cancer. Mucositis is a major complication that occurs in approximately 80% of patients receiving 5-FU and results in abdominal bloating as well as vomiting and diarrhea. oral mucositis (OM) are often very painful and compromise nutrition and oral hygiene as well as increase risk for local and systemic infection.

OM is characterized by an intense inflammatory reaction on the mucosa lamina propria cells, which results in activation of the transcription factor NF-kB. The activation of NF-kB leads to transcription of genes involved in the synthesis of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α. Agents known to attenuate the expression of cytokines have demonstrated efficacy in the prevention of experimental mucositis.

The use of atorvastatin were associated with reduced production of TNF-α and IL-1β and decreased neutrophil infiltration evidenced by histopathological analysis and Myeloperoxidase (MPO) activity. In addition, atorvastatin also reduced oxidative stress and induced an increase in non-protein sulfhydryl groups showing anti-inflammatory and immunomodulatory action.

详细描述

Chemotherapy has life-threatening or distressing side effects such febrile neutropenia, infections, mucositis, nausea, vomiting, fatigue. Mucositis is defined as inflammatory and/or ulcerative lesions of the oral and/or gastrointestinal tract that can be caused by high dose chemotherapy, Infectious disease, immune deficiency and medications..

Lesions of oral mucositis (OM) are often very painful and compromise nutrition and oral hygiene as well as increase risk for local and systemic infection. Mucositis can also involve other areas of the alimentary tract; for example, gastrointestinal (GI) mucositis can manifest as diarrhea. Thus, mucositis is a highly significant and sometimes dose-limiting complication of cancer therapy.

OM leads to an increased risk of microbial infections and often entails parenteral nutrition, long-lasting intake of analgesics and extended hospitalization periods. This causes substantial costs to the health system and, also has a considerable impact on the patient's quality of life. Furthermore, dose reduction might become necessary, which limits the efficacy of the antitumor therapy.

OM is characterized by an intense inflammatory reaction on the mucosa lamina propria cells, which results in activation of the transcription factor NF-kB. The activation of NF-kB leads to transcription of genes involved in the synthesis of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, and agents known to attenuate the expression of cytokines have demonstrated efficacy in the prevention of experimental mucositis.

Conventional chemotherapeutic drugs most frequently associated with mucositis include antimetabolites, such as 5-fluorouracil (5-FU), methotrexate, and purine antagonists. Anthracycline antitumor antibiotics (eg, doxorubicin) and taxanes (eg, paclitaxel and docetaxel) are other chemotherapeutic drugs that commonly cause mucositis.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Prevention
盲法
None

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Adult patients (>18 years old).
  • Colon cancer patients ???? who will receive adjuvant FOLFOX 6& FOLFIRI 6 for 6 cycles.
  • ECOG performance status 0-2
  • Adequate bone marrow function (white blood count ≥4,000/mm3, platelet count ≥100,000/mm3), liver function (serum total bilirubin <1.5 mg/dl), renal function (creatinine <1.5 mg/dl).

排除标准

  • Patients who have Clinical GIT mucositis or Periodontal disease.
  • Patients with other primary malignancy.
  • Patients receiving mTOR inhibitors (eg, rapamycin, everolimus, and temsirolimus), EGFR inhibitors (eg, bevacizumab and erlotinib) and tyrosine-kinase inhibitors (eg, sorafenib and sunitinib).
  • Hypersensitivity to Atorvastatin.
  • 6-Pregnant and lactating women. 7- Patients treated with ATV for any other indication. 8- Patient who already have a mucositis

研究组 & 干预措施

Atorvastatin group

Experimental

50 colorectal cancer patients receiving FOLFOX 6: (Oxaliplatin 85mg/m2 IV over 2 hrs + leucovorin 400mg/m2 IV over 2 hrs, followed by 5-FU 400mg/m2 IV bolus, followed by 5-FU 1,200mg/m2 /day IV x 2 days (total 2,400mg/m2 ) as a 46-48 hr continuous infusion. Repeat every 2 weeks) in addittion to atorvastatin (20 mg once daily) or FOLFIRI 6:( Irinotecan 180mg/m2 IV + leucovorin 400mg/m2 IV, followed by 5-FU 400mg/m2 IV bolus, followed by 5-FU 1,200mg/m2 /day IV x 2 days (total 2,400mg/m2 ) as a 46-48 hr continuous infusion. Repeat every 2 weeks) in addittion to atorvastatin (20 mg once daily) in addittion to atorvastatin (20 mg once daily)

干预措施: Atorvastatin 20mg (Drug)

结局指标

主要结局

incidence of mucositis

时间窗: 6 months

screening the patients seeking mucositis \& grading mucositis using Common Terminology Criteria for Adverse Events, CTCAE version 5 ( ranging from grade 1 of better outcome to 5 of worst outcome ) and evaluating the effect of atorvastatin on mucositis

次要结局

  • liver function test(6 months)
  • serum levels of tumor necrosis factor α (TNF-α)(6 months)
  • grade of mucositis(6 month)
  • Pain score(6 month)
  • Effect of mucositis on patient's daily life(6-months)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Radwa Salah Lotfy Abdel-Rahman

Clinical Pharmacist at nasser institute

Ain Shams University

研究点 (1)

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