In vitro cytotoxic dose-relation of cisplatin and sodium thiosulphate in human tongue and oesophageal squamous carcinoma cell lines.
BACKGROUND
Intraarterial chemotherapy of oral and oropharyngeal cancer with cisplatin (cis-diamminedichloroplatinum [II]) has experienced a revival in the last decade. Side-effects of the therapy were very low with concomitant systemic infusion of the neutralizing agent sodium thiosulphate. The requisite dose of the chemotherapeutic agent which safely leads to apoptosis of oral cancer cells has not yet been assessed in vitro, nor has the combination of cisplatin and sodium thiosulphate been examined for the potential reduction of cytotoxicity in oral cancer cells.


METHODS
In a panel of two tongue squamous cancer cell lines and an oesophageal cancer cell line as control and comparison, cisplatin (0.2-10 microgram/ml) was combined with sodium thiosulphate (0-0.5 mg/ml).


RESULTS
10 microgram/ml of cisplatin proved to be 100% antiproliferative, while any additional concentration of sodium thiosulphate decreased this effect. At the maximum dose of cisplatin, a sodium thiosulphate/cisplatin concentration relation of less than 6:1 still effected cytotoxic activity of >80%. An increase of cisplatin concentration led to higher cytotoxicity irrespective of sodium thiosulphate concentration. The oesophageal cell line was more sensitive to cisplatin and to sodium thiosulphate than the tongue cell lines.


CONCLUSIONS
In this study, it was found that high concentrations of cisplatin are necessary in oral cancer to reach cytotoxic levels which support high-dose intraarterial chemotherapy by which these levels might be reached. A sodium thiosulphate/cisplatin concentration ratio within the tumour of less than 6:1 may be allowed without compromising the cytotoxic activity of cisplatin.
Kovács
Adorján F
AF
Department of Maxillofacial Plastic Surgery, Johann Wolfgang Goethe-University Frankfurt Medical School, Frankfurt am Main, Germany. a.kovacs@em.uni-frankfurt.de
Cinatl
Jindrich
J
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002614:Chelating Agents / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004338:Drug Combinations; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D006801:Humans; D007269:Injections, Intra-Arterial; D013885:Thiosulfates / Q000008:administration & dosage*; D014062:Tongue Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002614:Chelating Agents; D004338:Drug Combinations; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin