fosfomycin and Carcinoma--Non-Small-Cell-Lung

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.. 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.

Topics: Acetylglucosaminidase; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Fosfomycin; Humans; Kidney; Lung Neoplasms; Vinblastine

The protective effects of fosfomycin and steroids on the nephrotoxicity induced by cisplatin in lung cancer patients were studied by measuring N-acetyl-beta-D-glucosaminidase (NAG) activity in 24-hour urine, creatinine clearance, serum creatinine and blood urea nitrogen as factors of nephrotoxicity. In control patients treated with anticancer drugs containing cisplatin but no supplemental fosfomycin or steroids, the 24-hour urine NAG level increased two-fold (15.5 +/- 7.5, p less than 0.01) over the pretreatment level (8.0 +/- 5.2) 3 days after anticancer therapy. Supplemental fosfomycin or steroids inhibited an increase in urinary NAG level 3 days after the anticancer therapy. There were, however, no significant changes in creatinine clearance, serum creatinine and blood urea nitrogen levels before and after anticancer and/or supplemental therapies. These results suggest the possibility that supplemental treatment with fosfomycin, like that with steroids, reduces cisplatin-induced nephrotoxicity, especially proximal tubular damage.

Topics: Acetylglucosaminidase; Blood Urea Nitrogen; Carcinoma, Non-Small-Cell Lung; Cisplatin; Creatinine; Fosfomycin; Humans; Hydrocortisone; Kidney Tubules, Proximal; Lung Neoplasms; Methylprednisolone; Middle Aged