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 < or = 0.05) to 83% (P < or = 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 < or = 0.001) and between 58 (P < or = 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 < or = 0.01) for NCI-H460 and by 126% (P < or = 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.