Effect of Losartan on the Incidence and Severity of Chemotherapy-Induced Mucositis in Gastrointestinal Cancer Patients

• Status: Not yet recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Mucositis is a common and clinically significant side effect of both anticancer chemotherapy and radiation therapy that can affect any portion of the gastrointestinal tract. Not only associated with an adverse symptom profile, but also it may limit patients' ability to tolerate treatment if not adequately prevented and managed. Moreover, it may be associated with secondary local and systemic infection and poor health outcomes, and generates additional use of healthcare resources resulting in additional costs.

Based on study of 38 patients of mean age sixty-one years old diagnosed with colorectal carcinoma were included to evaluate gastrointestinal adverse effect with different schedules of FOLFOX. Incidence of oral mucositis with FOLFOX-4 Is 76%, FOLFOX-6 is 62%, mFOLFOX-6 is 79% and FOLFOX-7 is 93%

Chemotherapy-induced mucositis is commonly described as a five-phase sequence:

initiation (0-2 days),upregulation and activation of messengers (2-3 days), signal amplification (2-5 days), ulceration with inflammation (5-14 days) and healing (14-21 days)

According to the model introduced by some studies the primary inducer involved in unleashing mucosal injury upon chemotherapy is the production of reactive oxygen species (ROS), leading to tissue inflammation and mucositis induction.

Inflammatory signaling pathways are upregulated during high reactive oxygen species states which further contribute to cytotoxicity. leading to the third step in the oral mucositis pathway. In this inflammatory phase, cytokines including Tissue Necrosis Factor alpha (TNF-α), prostaglandins, Nuclear factor Kappa β (NF-кβ), and interleukin (IL) 1β are released.

The cytotoxic effects of chemotherapy, inflammation, and reactive oxygen species-mediated DNA damage result in gradual apoptosis of mucosal epithelial cells. Ulcerative sites become relatively neutropenic which predisposes them to bacterial and yeast infections. These bacterial toxins further simulate the underlying inflammatory state through release of additional cytokines.

It is necessary to emphasize that oral mucositis is frequently documented only in its advanced phases owing to the requirements for clinical therapy and assistance. Therefore, the search for new active ingredients that could be used in the prevention (and even treatment) of oral and intestinal mucositis is of utmost importance.

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

Details

• Lead Sponsor: Ain Shams University
• Treatments: Losartan

Criteria

Inclusion Criteria:

1. Male or female patients aged 18 years old or more.

2. Patients diagnosed with gastrointestinal cancer eligible for chemotherapy

3. Eastern Cooperative Oncology Group (ECOG) performance ≤ 2.

4. Platelet count more than 100 × 10^9/L.

5. Absolute neutrophil count: greater than 1.5 × 10^9/L.

6. Aspartate aminotransferase level up to 2.5 times the upper limit normal.

7. Serum bilirubin level not more than 1.5 times the institutional upper limit normal.

8. Serum creatinine levels up to 1.5 mg% and 1.4 mg% for males and females respectively.

Exclusion Criteria:

1. Currently taking an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin receptor blocker (ARB)

2. Prior reaction or intolerance to an ARB or ACE inhibitor, including but not limited to angioedema.

3. Pregnant or breastfeeding women.

4. Females in child bearing age not currently taking a protocol allowed version of contraception: intrauterine device, Depo-formulation of hormonal contraception.

5. Patient reported history or electronic medical record history of kidney disease, defined as:

Any history of dialysis. History of chronic kidney disease stage IV. Estimated Glomerular Filtration Rate (eGFR) of < 30ml/min/1.73 m2 Other Kidney disease that in the opinion of investigator, would affect Losartan Clearance.

6. Patient reported dehydration and significantly decreased urine output in the past 72 hours.

7. Most recent systolic blood pressure prior to enrollment <110 mmHg.

8. Current participation in any other clinical investigation.

9. Currently taking any drug contraindicated with Losartan administration.