The protective effect of theophyline in cisplatin nephrotoxicity

Abstract

Cisplatin is a potent and a major anti-neoplastic drug in the treatment of a broad spectrum of malignancies. However, its clinical use is limited by renal tubular dysfunction that occurs in a significant percent of patients. The aim of the present study was to evaluate the possible protective effect of theophyline in the prevention of cisplatin-induced nephrotoxicity. The trial design was prospective, randomized, double-blinded and placebo controlled. Chemotherapeutic patients who received cisplatin at a dosage of at least 50 mg/m 2 alone or in combination with other chemotherapy agent(s) were included in the study. There were a total of 76 patients who were randomly divided into two groups. In group 1 (n = 38), placebo was advised; in group 2 (n = 38), patients received 4 mg/kg aminophyline as an intravenous loading dose, followed by theophyline in a dose of 200 mg three times daily orally for four consecutive days. The placebo group had 22 males and 16 females and the theophyline group had 26 males and 12 females. The mean age was 51 ± 17.6 years and the mean dose of cisplatin was 86.71 ± 43.18 mg. The prevalence of cisplatin nephrotoxicity in groups 1 and 2 was 7.9 and 5.3%, respectively, and the difference was not significant (P = 1). In addition, there was no significant association of cisplatin nephrotoxicity with age (P = 0.1), gender (P = 0.64) and mean dose of cisplatin (P = 0.8). These results indicate that prophy-lactic application of aminophyline and theophyline does not have a protective effect against cisplatin nephrotoxicity.

Efficacy of Antioxidant Supplements on Prevention and Amelioration of Cisplatin-Induced Nephrotoxicity: A Systematic Review and Meta-analysis of Randomized Controlled Trials

“…There were 672 enrolled patients in total, of whom 330 (49.10%) patients received antioxidant treatment whereas the remaining patients were on placebo or conventional treatment. Out of 12 randomized controlled trials, five were double-blinded (19,22,(26)(27)(28), one was single-blinded (17), and one was open-controlled (18).…”

“…The potential of various antioxidant treatments against CIN was assessed by measuring changes in BUN, eGFR, serum creatinine, creatinine clearance, and CIN incidence. The change in BUN was measured in two studies (18,21), change in eGFR in four studies (17,20,25,27), change in serum creatinine in five studies (17,18,21,25,27), change in creatinine clearance in two studies (18,28), and the incidence of CIN in four studies (19,22,26,27).…”

“…The randomized studies included in this review varied in their study design, structure, and methodology. Of 10 studies identified for analysis in this study, five were classified as high-quality (17,19,22,27,28) and five as low-quality (18,20,21,25,26).…”

Role of Nigella sativa and Its Constituent Thymoquinone on Chemotherapy-Induced Nephrotoxicity: Evidences from Experimental Animal Studies

“…Therefore, it is important to develop effective strategies in order to prevent nephrotoxicity from anti-cancer agents and investigation in this field constitutes an active area of research. Several agents, such as L-arginine [4], vitamin E alone [5] or combined with selenium [6], magnesium [7], vitamin C (combined with losartan) [8], ebselen [9], amifostine [10], theophylline [11] have been evaluated in order to investigate on their ameliorative effects on chemotherapy-induced nephropathy.…”

The efficacy of theophylline in preventing cisplatin-related nephrotoxicity in patients with cancer

“…It was presented in a prospectively randomized double-blind and placebo controlled study, which was conducted by Mousavi et al 37 that aminophylline and theophylline did not have any protective effect against cisplatin nephrotoxicity in 76 patients. However, kidney functions were evaluated by considering only the creatinine levels 1 day before and 5 days after the cisplatin administration in that study.…”