IN-VITRO ANTITUMOR-ACTIVITY OF REBECCAMYCIN ANALOG (NSC-NUMBER-655649) AGAINST PEDIATRIC SOLID TUMORS

Purpose: This study determined the in vitro antitumor activity of a re beccamycin analog (NSC# 655649) using tetrazolium/formazan (MTT) and c lonogenic assays against established pediatric cell lines and solid tu mor specimens obtained from children. Materials and Methods: Tumor cel ls from 14 established cell lines and 20 patient specimens were expose d in vitro for 1 hour to NSC# 655649 at concentrations ranging from 0. 015 to 15.0 mu M. The cytotoxicity (IC50)of this agent against establi shed cell lines was determined using both the MTT (cytotoxic) and clon ogenic/soft agar cloning (cytostatic) assays. Tumor specimens from chi ldren undergoing biopsy or surgical resection were also evaluated in v itro against NSC# 655649 using the clonogenic assay. For studies using patient specimens, antitumor activity was measured by comparing the n umber of tumor colonies from NSC# 655649-treated cells with those from solvent-treated controls. Results: These studies showed that the mean ICS(50)s using the MTT and clonogenic assays using established solid tumor cell lines were 0.94 and 0.51 mu M respectively. In general, for cell lines tested using both types of assays, the clonogenic assay re sulted in a smaller IC50 The overall in vitro responses (less than or equal to 50% survival compared to controls) using patient tumor specim ens and the clonogenic assay were 35% (1.5 mu M), 60% (7.5 mu M), and 80% (15.0 mu M), Of the 9 patients with neuroblastoma, responses to NS C# 655649 were seen in 33% (1.5 mu M), 58% (7.5,uM), and 92% (15.0 mu M) of the specimens. Prior chemotherapy did not appear to adversely af fect in vitro responses. Conclusions: NSC# 655649 appears to have broa d antitumor activity ill vitro against pediatric malignancies at drug concentrations achieved during adult phase I clinical trials, These st udies support the further development of NSC# 655649 for solid tumors in children.