DECADOSE EFFECTS OF CISPLATIN ON SQUAMOUS-CELL CARCINOMA OF THE UPPERAERODIGESTIVE TRACT .1. HISTOCULTURE EXPERIMENTS

There is substantial laboratory and clinical evidence that solid tumor s rapidly acquire cellular resistance to cisplatin. Experiments with h uman carcinoma cell lines and clonogenic assays indicate that resistan ce is usually mild to moderate and can be circumvented with higher con centrations of drug. The purpose of this investigation was to test thi s hypothesis with a histoculture assay of human upper aerodigestive tr act (UADT) carcinomas. Using a sponge-gel supported histoculture, 43 t umor specimens from patients with squamous cell carcinoma (SCC) of the UADT were grown and exposed to cisplatin. Growth inhibition by the dr ug, in concentrations equivalent to peak therapeutic doses (1.5 mu g/m L) and concentrations 10 and 25 times greater (15 and 37.5 mu g/mL), w ere measured in specimens from patients with previously untreated and recurrent lesions. In vitro, the overall rate of sensitivity of the tu mor samples to cisplatin concentrations of 1.5, 15, and 37.5 mu g/mL w ere 22%, 62%, and 83%, respectively. In patients with previously untre ated disease, the respective rates were 25.9%, 63.3%, and 79.3%, as co mpared with 10.0%, 55.6%, and 85.6%, respectively, for patients with r ecurrent disease. The response difference between cisplatin concentrat ions of 1.5 and 15 mu g/mL was statistically significant. The ''decado se'' effect of cisplatin on growth inhibition was 2.44-fold for untrea ted lesions and 5.56-fold for recurrent tumors. The results indicate t hat resistance to standard doses of cisplatin by SCC of the UADT can b e substantially overcome with a decadose (standard dose x 10) increase and is more pronounced in tumors from patients with recurrent disease . Progress toward improving survival of patients may be possible by in corporating decadose cisplatin therapy into a multimodality treatment plan.