In vivo interaction of cis-platinum and fosfomycin on squamous cell carcinoma.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Tandy
J R
JR
Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas, USA.
Tandy
R D
RD
Farris
P
P
Truelson
J M
JM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005578:Fosfomycin / Q000494:pharmacology* / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D005578:Fosfomycin; D002945:Cisplatin