Combretastatin A-4 prodrug inhibits growth of human non-small cell lung cancer in a murine xenotransplant model

Background. Combretastatin A-4 prodrug (CA-4PD) has been identified as a po tent antivascular agent in various rodent tumor models. The aim of this stu dy was to investigate the effect of CA-4PD on human non-small cell lung can cer (NSCLC). Methods. Cytostatic and cytotoxic effects of CA-4PD on selected NSCLC cells , Cole-699 and KNS-62, were studied in vitro. After subcutaneous xenotransp lantation the effect of systemically administrated CA-4PD on tumor growth w as investigated in vivo. A newly established orthotopic xenotransplant mode l was employed to estimate prolongation of survival after intrapulmonary tu mor induction with secondary metastatic disease. Results. In vitro, CA-4PD displayed a time and dose dependent antiprolifera tive effect on human lung cancer cells. In vivo, CA-4PD significantly delay ed growth of subcutaneously induced lung cancer. This growth delay was tran slated into a prolongation of survival in the metastasizing orthotopic xeno transplant model. Conclusions. In vitro CA-4PD inhibits proliferation of NSCLC cells, most li kely by disruption of microtubule assembly. In vivo, systemic treatment inh ibits growth of subcutaneously xenotransplanted tumors by an antivascular e ffect. In the case of metastasizing human lung cancer this translated into a prolongation of survival. (Ann Thorac Surg 2001;71:1657-65) (C) 2001 by T he Society of Thoracic Surgeons.