Histology and sensitivity to anticancer drugs of two human non-small cell lung carcinomas implanted in the pleural cavity of nude mice

We have established two metastatic models of human non-small cell lung carc inoma (NSCLC)-the NC1-H460 large-cell carcinoma and the A549 adenocarcinoma -by inoculating tumor cells into the pleural space of nude mice. The object ives of this work were as follows: (a) to study the histological characteri stics 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 investiga te the antitumor activity of S 16020-2, a new olivacine derivative, current ly 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 dia phragm, with histological characteristics consistent with the human patholo gy, Anticancer drugs used for the treatment of NSCLC, such as cisplatin, do xorubicin, vinblastine, and etoposide, enhanced the life span of treated mi ce in the two models and were more active in the NCI-H460 than in the A539 model. The increases of survival time as compared to control groups were fr om 60 (P less than or equal to 0.05) to 83% (P less than or equal to 0.01) and from 21 to 40% for NCI-H460 and A549, respectively, Vinorelbine, paclit axel, and irinotecan showed similar activities in the two models and increa sed the survival of treated mice by between 38 and 79% (P less than or equa l to 0.001) and between 58 (P less than or equal to 0.01) and 78% in the NC I-H460 and A549 models, respectively. However, none of these drugs was cura tive, reflecting the resistance of this disease to chemotherapy. S 16020-2 exhibited a remarkable antitumor activity, increasing the surviva l by 82% (P less than or equal to 0.01) for NCI-H460 and by 126% (P less th an or equal to 0.001) for A549. This drug was among the most active compoun ds in these models, thereby indicating its potential for the chemotherapy o f this disease.