The relative effectiveness of analogues of cisplatin in the experimental chemotherapy of human non-small-cell lung cancer and neuroblastoma grown as multicellular spheroids.
We compared cisplatin (cis-DDP) and two of its analogues, carboplatin (JM8, CBDCA) and iproplatin (JM9, CHIP) for their ability to retard the growth of multicellular tumour spheroids. The spheroids were derived from two human tumours, a neuroblastoma and a non-small-cell lung cancer. To produce a given level of regrowth delay in lung cancer spheroids, carboplatin and iproplatin were required at concentrations approximately 10 times that of cis-DDP. In the neuroblastoma spheroid experiments, iproplatin and cis-DDP produced the same level of regrowth delay when iproplatin was present at a concentration greater than 10 times that of cis-DDP. Carboplatin also required much higher concentrations than cis-DDP to produce equivalent regrowth delay in neuroblastoma. The dose-response curve produced by carboplatin on neuroblastoma spheroids displayed a pronounced shoulder in the low-dose region; this phenomenon was not seen with cis-DDP. 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 lung cancer, since total free-drug exposure of patients to carboplatin may be up to 16-fold greater than with cis-DDP. However, one must be cautious about generalizing on the basis of results from only two cell lines as well as applying in vitro data to clinical situations.
Russell
J
J
Radiation Oncology Research Group, Beatson Oncology Centre, Belvidere Hospital, Glasgow, Scotland.
Adam
J
J
Wheldon
T E
TE
Kaye
S B
SB
D016190:Carboplatin; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D009944:Organoplatinum Compounds; C023359:iproplatin; D016190:Carboplatin; D002945:Cisplatin