Nephroprotective Effect of Pentoxifylline Against Cisplatin in Patients With Head and Neck Cancer

Not Applicable

Not yet recruiting

• Conditions: Pentoxifylline, Cisplatin, Nephrotoxixcity
• Interventions: Drug: cisplatin with standard hydration with normal saline; Drug: Pentoxifylline 400 mg SR tablets

• Registration Number: NCT05640817
• Lead Sponsor: Tanta University

Brief Summary

Head and neck squamous cell carcinoma (HNSCC) encompasses a variety of tumors originating in the lip, oral cavity, hypopharynx, oropharynx, nasopharynx and larynx. It is the sixth most common malignancy worldwide accounting for approximately 6% of all cancer cases (Rettig and D'Souza., 2015). HNSCC represents the third most common cause of cancer death worldwide. Platinum based regimens represent cornerstone in its treatment (Galbiattiet al., 2013).

Cisplatin (cis-diammine dichloroplatinum (II), CDDP) is an inorganic platinum-based chemotherapeutic agent that is widely used in treatment of various solid malignancies as head and neck, lung, testis, ovarian, and bladder cancers (Aparecida et al., 2012). The use of cisplatin is frequently limited by significant side effects including bone marrow suppression, peripheral neuropathy, ototoxicity, anaphylaxis and nephrotoxicity with the latter representing the main dose limiting one (Aparecida et al., 2012).

Acute kidney injury (AKI), distal renal tubular acidosis, renal concentrating defect, transient proteinuria, hyperuricemia, Fanconi-like syndrome, hypomagnesemia, hypocalcemia, renal salt wasting, erythropoietin deficiency, thrombotic microangiopathy, and chronic renal failure are among the renal side effects of cisplatin (Miller et al., 2010).Renal function deterioration is seen in 25% to 35% of patients treated with a single dose of cisplatin (Miller et al., 2010).Cisplatin-induced injury to renal epithelial cells results in the production of various inflammatory factors, including TNF-α. Cisplatin also increases ROS production, which leads to the activation of apoptosis and necrosis pathways (Miller et al., 2010).

Pentoxifylline (PTX), a nonspecific phosphodiesterase inhibitor, was first considered in the treatment of peripheral vascular diseases (Nasiri-Toosi et al., 2013). PTX has anti-inflammatory effects as it down regulates several pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) and IL-6 (Mostafa-Hedeab et al., 2022). In addition, PTX has gained considerable interest as a reactive oxygen species (ROS) scavenger, and several studies show its potential antioxidant effects (Zhang et al., 2016). Several studies evaluate the renoprotective effects of PTX against drug-induced nephrotoxicity (Ramesh and Reeves, 2002; Kasap et al., 2013;Nasiri-Toosi et al.,2013; Panahi-Shokouh etal., 2020; Alorabi et al., 2022).

Detailed Description

Not available

Study Timeline

• Status Verified: 2022-11
• Study First Submitted: 2022-11-30
• Study First Submitted QC: 2022-11-30
• Last Update Submitted: 2022-11-30
• Study Start: 2022-12
• Study First Posted: 2022-12-07
• Last Update Posted: 2022-12-07
• Primary Completion: 2023-05
• Study Completion: 2023-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 as control group	cisplatin with standard hydration with normal saline	cisplatin with standard hydration with normal saline
Group two as Pentoxifylline	Pentoxifylline 400 mg SR tablets	receive cisplatin with standard hydration with normal saline and Pentoxifylline 400 mg SR tablets twice daily for three cycles.

Primary Outcome Measures

Name	Time	Method
nephrotoxicity improvement as measured by CTACE version 5.0	up to 6 months

Secondary Outcome Measures

Name	Time	Method
Kidney injury molecule 1 decrease serum level	up to 6 months