Nephroprotective Effect of Pentoxifylline Against Cisplatin in Patients With Head and Neck Cancer
Status:
Not yet recruiting
Trial end date:
2023-06-01
Target enrollment:
Participant gender:
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).