fosfomycin and Carcinoma--Squamous-Cell

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

This study investigates the effect of fosfomycin on the tumoricidal efficacy of cisplatinum.. Prospective study utilizing the FaDu squamous cell carcinoma cell line and a nude mouse tumor xenograft model.. Tumor cell growth was assessed in vitro in the presence of cisplatinum and/or fosfomycin utilizing the MTT assay. An optimal cisplatinum dose and dosing schedule was established in a nude mouse tumor xenograft model of squamous cell carcinoma. Using this model, fosfomycin was tested at three dosages and tumor growth monitored over 4 weeks.. Mice treated with cisplatinum and fosfomycin had smaller tumors than those treated with cisplatinum alone (P<.01).. This study is the first demonstration that fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum in vivo. This suggests that fosfomycin may be useful in preventing cisplatinum-induced ototoxicity and nephrotoxicity in humans without altering the tumor response rate.

Topics: Animals; Anti-Bacterial Agents; Carcinoma, Squamous Cell; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Fosfomycin; Hearing Loss, Sensorineural; Kidney Diseases; Mice; Mice, Inbred BALB C; Mice, Nude; Prospective Studies; Tumor Cells, Cultured

Fosfomycin has been shown to be otoprotective and nephroprotective against cisplatin-induced toxic reactions. This study tests whether fosfomycin inhibits the anticancer effect of cisplatin.. Three squamous cell carcinoma cell lines were used to determine the effect of fosfomycin on cisplatin-induced tumoricidal activity. Cells were grown in 96 well plates with fosfomycin alone, cisplatin alone, or fosfomycin and cisplatin together. Cell survival was then measured by a colorimetric technique using 3-4,5-dimethylthiazol-2-yl 2,5 diphenyltetrazolium bromide (MTT).. There was no decrease in the effectiveness of cisplatin in killing human squamous cell carcinoma in vitro when fosfomycin was present in concentrations of up to 400 mg/L. One cell line also showed killing at high concentrations of cisplatin, but not at low concentrations.. Fosfomycin protects against cisplatin-induced toxic reactions and does not inhibit tumoricidal activity in vitro. In addition, one cell line showed relative resistance to cisplatin at low doses, but was effectively killed with high doses of cisplatin. This is the ideal situation for use of fosfomycin so that higher doses of cisplatin may be given with renal and otologic protection.

Topics: Carcinoma, Squamous Cell; Cisplatin; Colorimetry; Dose-Response Relationship, Drug; Fosfomycin; Humans; Time Factors; 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