fosfomycin and Head-and-Neck-Neoplasms

Cis-platinum is the most frequently used chemotherapeutic agent for the treatment of head and neck squamous cell carcinoma (SCCA). Ototoxicity and nephrotoxicity continue to be the primary dose-limiting toxicities encountered. Fosfomycin, a broad-spectrum antibiotic, has been previously shown to be both otoprotective and nephroprotective against cis-platinum toxicity. Previous in vitro work demonstrated that fosfomycin does not inhibit the tumoricidal actions of cis-platinum. This study tests whether fosfomycin inhibits cisplatinum in vivo.. An SCCA cell line was grown in vivo in four groups of nude mice, which then received no treatment, standard-dose cis-platinum, high-dose cis-platinum, or high-dose cis-platinum with fosfomycin.. Fosfomycin did not inhibit the tumoricidal activity of cis-platinum. Mice treated with fosfomycin also had longer survival, which is probably due to lessening of immediate cis-platinum systemic toxicity.. This study shows that fosfomycin in combination with cis-platinum may be useful in treating advanced, and possibly relatively chemoresistant, SCCA of the head and neck.

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; Dose-Response Relationship, Drug; Drug Interactions; Fosfomycin; Head and Neck Neoplasms; Mice; Mice, Inbred BALB C; Tumor Cells, Cultured

A group study of chemotherapy for head and neck squamous cell carcinoma, using CDDP, THP and PEP, was carried out on 32 cases at the department of Otolaryngology, University of Tokyo, and 7 affiliated hospitals. The combined chemotherapy, which we call "PTP therapy", consisted of 30 mg/m2 of THP on day 1, 70 mg/m2 of CDDP on day 2, and 5 mg/body/day of PEP on 4 successive days. The overall response rate was 78.1% (CR: 15.6%; PR: 62.5%). No major side effect was observed in any case. PTP therapy is useful in neoadjuvant chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Dexamethasone; Doxorubicin; Drug Administration Schedule; Female; Fosfomycin; Head and Neck Neoplasms; Humans; Male; Metoclopramide; Middle Aged; Peplomycin

Creatinine clearance and beta-D-acetyl-glucosaminidase (NAG) were useful markers for the evaluation of the renal function of 57 cases of head and neck cancer treated with 60 mg/m2 cis-platinum (CDDP). There was a significant correlation between creatinine clearance and NAG values for (r = -0.4820, p less than 0.01). The nadir of creatinine clearance and NAG values were observed between 2 and 3 weeks after administration of CDDP. After 2 courses of chemotherapy with CDDP, more nephrotoxicity was observed in the cases received prior CDDP therapy, than cases without chemotherapy statistically. Combined chemotherapy with CDDP and 5-FU (CF therapy) caused more renal damage, comparing with other combined chemotherapy such as COP therapy (CDDP, vincristine and peplomycin), and CAP therapy (CDDP, aclacinomycin and cyclophosphamide). Early recovery from the renal damage following CDDP therapy was detected in the cases given Fosfomycin (FOM). This results suggest that FOM would be effective for decreasing the nephrotoxicity by CDDP.

Topics: Acetylglucosaminidase; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Creatinine; Drug Evaluation; Female; Fosfomycin; Head and Neck Neoplasms; Hexosaminidases; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Predictive Value of Tests