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

Abstract

Objective: Cisplatin is a potent antineoplastic agent used and its major limiting side effect is nephrotoxicity. The aims of the study are early detection of acute kidney injury (AKI) with biomarkers and investigation of the potential nephron-protective effects of theophylline. Methods: Glomerular filtration rates (GFR), neutrophil gelatinase-associated lipocalin (NGAL), cystatin C were measured at 5th day of treatment in all of the patients. In addition, these parameters were measured repeatedly after the administration of cisplatin, at 2nd hour, 5th and 20th days. Patients: Sixty patients who are planned to receive cisplatin for the first time were included in the study. Patients were divided into two groups as Group 1 (n ¼ 30) (standard treatment arm) and Group II (n ¼ 30) (theophylline arm). Results: In both groups after the administration of cisplatin, GFR showed a significant decrease within time (p ¼ 0.006). Urine NGAL levels were significantly high after 2 h of cisplatin administration (p < 0.001), no significant difference was observed between groups. However, when the time*group effects were considered together, higher NGAL levels were detected in the group not receiving theophylline (p ¼ 0.025). After 5 days of cisplatin administration, urine protein levels were significantly higher in both groups (p < 0.001). Conclusion: Results showed that urine NGAL level is a superior biomarker compared to serum creatinine and serum cystatin C in the detection of early AKI. Theophylline was found not to bring a complete protection for the kidneys, but less nephrotoxicity was developed when compared to the group not receiving theophylline. ARTICLE HISTORY

Urine biomarkers of acute kidney injury in noncritically ill, hospitalized children treated with chemotherapy

“…Several potential treatments of both Cis‐ and Ifos‐mediated AKI have been shown to mitigate renal tissue damage . A few human studies suggest that ameliorating chemotherapy‐associated AKI with medication is possible . Early and specific AKI markers will enhance future trials of Cis‐ and Ifos‐nephrotoxicity prevention.…”

Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy

“…A study of patients ( n = 33) revealed an AUC-ROC value for NGAL of 0.87 at 12 and 24 h. 21 Other studies have also revealed similar findings with an AUC-ROC value of 0.80 at 24 h signifying important predictive value for NGAL to reflect AKI. 56 Recent data also suggest that elevations in urinary NGAL may even be able to detect AKI as early as 2 h. 59 Interestingly, patients with a slow recovery from AKI had earlier and higher increases in urinary NGAL levels. 57 The time points selected for NGAL quantification are important.…”

Potential synergistic effect of phosphodiesterase inhibitors with chemotherapy in lung cancer

“…In our study, the addition of sildenafil plus theophylline with or without roflumilast combined with carboplatin or cisplatin showed increased apoptosis when compared with platinum-based drugs alone. Despite the high pharmacological doses 71 and questionable protective effect against cisplatin nephrotoxicity 72 , theophylline has been proposed as a potential anti-cancer drug combined with chemotherapeutic regimens for more than a decade. 36 , 43 , 73 , 74 Specifically, the synergistic effect of theophylline with chemotherapeutic drugs comes from the induction of apoptosis and the interference with the cell cycle.…”