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Histology and Sensitivity to Anticancer Drugs of Two Human Non-Small Cell Lung Carcinomas Implanted in the Pleural Cavity of Nude Mice

Institut de Recherches Servier, Division de Cancérologie Expérimentale, 92150 Suresnes, France

We have established two metastatic models of human non-small cell lung carcinoma (NSCLC)—the NCI-H460 large-cell carcinoma and the A549 adenocarcinoma—by inoculating tumor cells into the pleural space of nude mice. The objectives of this work were as follows: (a) to study the histological characteristics and growth and dissemination patterns of these tumors in nude mice; (b) to assess their sensitivity to drugs that have demonstrated significant clinical therapeutic effect in the treatment of NSCLC; and (c) to investigate the antitumor activity of S 16020-2, a new olivacine derivative, currently in Phase II clinical evaluation.

In each of the two models, all animals developed lung tumors, resulting in 100% mortality. Histopathological study showed that these two tumors spread locally to contiguous structures, including the mediastinal pleura and diaphragm, with histological characteristics consistent with the human pathology. Anticancer drugs used for the treatment of NSCLC, such as cisplatin, doxorubicin, vinblastine, and etoposide, enhanced the life span of treated mice in the two models and were more active in the NCI-H460 than in the A549 model. The increases of survival time as compared to control groups were from 60 (P 0.05) to 83% (P 0.01) and from 21 to 40% for NCI-H460 and A549, respectively. Vinorelbine, paclitaxel, and irinotecan showed similar activities in the two models and increased the survival of treated mice by between 38 and 79% (P 0.001) and between 58 (P 0.01) and 78% in the NCI-H460 and A549 models, respectively. However, none of these drugs was curative, reflecting the resistance of this disease to chemotherapy.

S 16020-2 exhibited a remarkable antitumor activity, increasing the survival by 82% (P 0.01) for NCI-H460 and by 126% (P 0.001) for A549. This drug was among the most active compounds in these models, thereby indicating its potential for the chemotherapy of this disease.

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