fosfomycin and Lung-Neoplasms

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

An antibiotic FOM was found to be preventive of the side effect of an antineoplastic drug CDDP on the peripheral T lymphocytes in lung cancer patients. Whereas finding a significant decrease in T3+ cells (p less than 0.01) and T4+ subset (p less than 0.05) with CDDP alone, the initial levels of these cell populations were kept unchanged in combination with FOM. T8+ subset showed no substantial change. A protective effect of FOM on T4+ subset was suggested to be an additional aspect of its action at least in combination with CDDP.

Topics: Aged; Cisplatin; Clinical Trials as Topic; Drug Therapy, Combination; Female; Fosfomycin; Humans; Lung Neoplasms; Male; Middle Aged; T-Lymphocytes

We experienced successful treatment of postoperative severe pneumonia of Methicillin-resistant Staphylococcus aureus (MRSA) with combination therapy of Arbekacin (ABK) and Fosfomycin (FOM) in three lung cancer patients. Case 1 was a advanced age of seventy-nine man who had had right upper lobectomy. Case 2 was a 61-year-old man who had had left lower lobectomy and extended bilateral mediastinal lymph-node dissection through the median sternotomy. And case 3 was a 59-year-old man who had suffered from pulmonary embolism after right pneumonectomy and partial resection of left atrium and superior vena cava. All cases were immuno-compromised patients and super-infected with Gram-negative rods, and Pseudomonas aeruginosa in case 1 and case 3. Clinical symptoms were improved after the start of administration of ABK and FOM inspite of ineffectiveness of prior treatment with other antibiotics. We added staggered chemotherapy of Sulbactam/Cefoperazone (SBT/CPZ) and Ceftazidime (CAZ) for case 1 and case 3 respectively. Thus, the combination therapy of ABK and FOM might be useful for severe pneumonia of MRSA in the immunocompromised patients, and the combined staggered chemotherapy of beta-lactum agents and above would be the first choice in the treatment for the case involving Pseudomonas aeruginosa.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Therapy, Combination; Fosfomycin; Humans; Immunocompromised Host; Lactams; Lung Neoplasms; Male; Methicillin Resistance; Middle Aged; Pneumonia, Bacterial; Postoperative Complications; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus

Topics: Aged; Cisplatin; Fosfomycin; Humans; Kidney Diseases; Kidney Tubules; Lung Neoplasms; Male; Middle Aged

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

To elucidate the influence of fosfomycin (FOM) on the anti-cancer effect of cisplatin (CDDP), experimental chemotherapy of CDDP with or without FOM was performed. A human lung cancer cell line, HLC-1 serially transplanted into nude mice was treated with CDDP 10 mg/kg (i.p.). Tumor doubling time in CDDP group and CDDP + FOM group are 26.78 +/- 6.3 days and 33.90 +/- 11.82 days respectively, and they are significantly elongated compared to control group. Serum NAG level in CDDP + FOM group was significantly lowered. Therefore, we concluded that anti-tumor effect of CDDP was not diminished by FOM combination.

Topics: Adenocarcinoma; Animals; Cisplatin; Drug Therapy, Combination; Female; Fosfomycin; Kidney Diseases; Lung Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Transplantation