Effectiveness of cis-platin and carboplatin in the chemotherapy of squamous cell carcinoma grown as multicellular spheroids.
We compared cis-platin (DDP) and its analogue, carboplatin (JM8, CBDCA) in their ability to inhibit spheroid growth. The activities of DDP and JM8 were also compared in an antimetabolic assay for their ability to inhibit (3H)-thymidine incorporation in multicellular tumor spheroids. The spheroids were derived from a squamous cell carcinoma cell line HN-1, originally derived from a tumor of the tongue. To produce equal levels of growth delay in spheroids, carboplatin was required at concentrations approximately 16 times that of DDP. Carboplatin also required much longer incubation periods than DDP to produce equivalent growth delay and proportions of cured spheroids. Reflecting the initial response to chemotherapy, the antimetabolic assay showed that carboplatin was required at higher concentrations and longer exposure times to produce equal inhibition of the nucleotide precursor thymidine. These findings may have implications for the clinical use of these drugs and in particular would support a role for carboplatin in the treatment of squamous cell carcinoma of the head and neck, since total free-drug exposure of patients to carboplatin may be up to 16-fold greater than with DDP, and the clinical side effects of carboplatin have been shown to be well tolerated. However, one must be cautious about applying in vitro data to clinical situations.
Department of Radiotherapy, University Hospital Nijmegen, The Netherlands.
J H
JH
Schwachöfer
R P
RP
Crooijmans
J
J
Hoogenhout
H B
HB
Kal
A G
AG
Theeuwes
D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin; D002294:Carcinoma, Squamous Cell; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014062:Tongue Neoplasms; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D014316:Tritium; D016190:Carboplatin; D002945:Cisplatin; D013936:Thymidine