Protective effects of fosfomycin on cisplatin-induced nephrotoxicity in patients with lung cancer.
METHODS
Protective effects of fosfomycin on cisplatin-induced nephrotoxicity have been previously reported, however, the proper time, duration and dosage of its administration were uncertain. Therefore, we investigated the protective effect of concurrent administration of twice-daily doses of 2 g fosfomycin for 5 days in 13 cisplatin-naïve lung cancer patients who were due to receive a single dose per cycle of 100 mg/m2 cisplatin. On each chemotherapeutic cycle, patients were randomly given cisplatin alone or cisplatin plus fosfomycin every 4 weeks for a maximum of 4 consecutive cycles. Indicators of nephrotoxicity, urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, serum creatinine (Scr) and creatinine clearance (Clcr) were determined the day before and at day 3 and day 6 after cisplatin administration. Results were compared and statistically analyzed by the non-parametric Mann-Whitney's test. We found that the NAG activities obtained on day 0, day 3 and day 6 of the fosfomycin cycles were comparable to values obtained during the control cycles (p > 0.05). Moreover, the NAG activities on day 3 of both treatment cycles were significantly elevated from baseline (p < 0.01) and had normalized on day 6. There were no significant changes in serum creatinine and creatinine clearance.


CONCLUSIONS
High-dose cisplatin induced reversible elevation of urinary NAG and concurrent administration of low-dose fosfomycin for 5 days had no effect on the enzymuria. In the prevention of cisplatin nephrotoxicity, a further study using dose escalation (8 to 12 g/d) of fosfomycin administered 2 to 3 days prior to cisplatin are required to demonstrate its nephroprotective effects.
Rojanasthien
N
N
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Thailand. nrojanas@med.cmu.ac.th
Kumsorn
B
B
Atikachai
B
B
Leotrakul
S
S
Thongprasert
S
S
D000118:Acetylglucosaminidase / Q000652:urine; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005578:Fosfomycin / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008175:Lung Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage
D005578:Fosfomycin; D014747:Vinblastine; D000118:Acetylglucosaminidase; D002945:Cisplatin