“Decadose” Effects of Cisplatin on Squamous Cell Carcinoma of the Upper Aerodigestive Tract. I. Histoculture Experiments

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Abstract
There is substantial laboratory and clinical evidence that solid tumors rapidly acquire cellular resistance to cisplatin. Experiments with human carcinoma cell lines and clonogenic assays indicate that resistance is usually mild to moderate and can be circumvented with higher concentrations of drug. The purpose of this investigation was to test this hypothesis with a histoculture assay of human upper aerodigestive tract (UADT) carcinomas.Using a sponge‐gel supported histoculture, 43 tumor specimens from patients with squamous cell carcinoma (SCC) of the UADT were grown and exposed to cisplatin. Growth inhibition by the drug, in concentrations equivalent to peak therapeutic doses (1.5 μg/mL) and concentrations 10 and 25 times greater (15 and 37.5 μg/mL), were measured in specimens from patients with previously untreated and recurrent lesions.In vitro, the overall rate of sensitivity of the tumor samples to cisplatin concentrations of 1.5, 15, and 37.5 μg/mL were 22%, 62%, and 83%, respectively. In patients with previously untreated disease, the respective rates were 25.9%, 63.3%, and 79.3%, as compared with 10.0%, 55.6%, and 85.6%, respectively, for patients with recurrent disease. The response difference between cisplatin concentrations of 1.5 and 15 μg/mL was statistically significant. The “decadose” effect of cisplatin on growth inhibition was 2.44‐fold for untreated lesions and 5.56‐fold for recurrent tumors.The results indicate that resistance to standard doses of cisplatin by SCC of the UADT can be substantially overcome with a decadose (standard dose × 10) increase and is more pronounced in tumors from patients with recurrent disease. Progress toward improving survival of patients may be possible by incorporating decadose cisplatin therapy into a multimodality treatment plan.