Comparative effect of cisplatin, spiroplatin, carboplatin and iproplatin in a human tumor clonogenic assay

Summary

A modified double-layer Hamburger and Salmon cloning assay was used to test cisplatin and its analogs (spiroplatin, carboplatin and iproplatin) on fresh tumor samples from 63 patients with a variety of non-hematological malignancies. Among them were 18 breast cancers, 17 ovarian cancers and 7 of unknown primaries. Half the patients received prior chemotherapy. Cisplatin regimens were given in 16 cases. When possible, cells were exposed for 1 h to each drug in concentrations of 0.1 Μg/ml and 1.0 Μg/ml for cisplatin and spiroplatin, 1.0 Μg/ml and 10 Μg/ml for carboplatin and iproplatin. A ≧50% cell kill with at least one drug was found in 20 samples including 8 ovarian cancers, 3 breast cancers and 1 unknown primary. A ≧70% cell kill was seen in 2 samples with cisplatin, 3 with spiroplatin and carboplatin, and 6 with iproplatin. There was only partial cross-resistance between cisplatin and its analogs. Among 57 paired comparisons of cisplatin with spiroplatin, 2 showed drug sensitivity to cisplatin alone, 6 to spiroplatin alone, and 6 to both. The same sort of observation was made with carboplatin. The lack of cross-resistance between cisplatin and iproplatin was particularly striking: among 53 pairs, 6 were sensitive to cisplatin alone, 8 to iproplatin alone, and 2 to both. About 20% of the samples that were resistant to cisplatin were sensitive to iproplatin. Our data show hints of activity in breast and ovarian cancers with all analogs and suggest that they will achieve clinical antitumor activity similar to that they will achieve clinical antitumor activity similar to that of cisplatin. The in vitro evidence of incomplete cross-resistance between cisplatin and its analogs should be investigated further.