Abstract
Purpose: This study was performed to evaluate the activity of the multitargeted antifolate (MTA or LY231514) against a broad range of human tumors taken directly from patients. Materials and methods: Human tumor colony-forming units were treated with MTA at concentrations of 0.1, 1.0, and 10 μg/ml in 1-h exposure studies. The responses of a limited number of specimens were also evaluated concurrently in 1-h exposures to cisplatin, fluorouracil, irinotecan, and/or paclitaxel. Results: Of 358 specimens plated in the 1-h exposure studies, 148 (41%) were evaluable. Overall, responses were observed in 3% of specimens (4/144) at 0.1 μg/ml, 11% (17/148) at 1.0 μg/ml, and 23% (33/141) at 10 μg/ml. In this range of concentrations achievable clinically, there was a significant concentration-response relationship. At 10 μg/ml in the 1-h exposure studies, the response rate in colorectal cancer specimens was 32% (9/28), and the response rate in non-small-cell lung cancer was 25% (6/24). Responses were also observed in several chemoresistant tumors, including renal cell carcinoma, hepatocellular carcinoma, mesothelioma, and pancreatic carcinoma. The activity of MTA was not completely cross-resistant with that of cisplatin, fluorouracil, irinotecan, and paclitaxel. Conclusions: MTA demonstrated in vitro activity against a spectrum of tumors, including several tumors generally considered chemoresistant.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received: 18 September 1998 / Accepted: 21 December 1998
Rights and permissions
About this article
Cite this article
Britten, C., Izbicka, E., Hilsenbeck, S. et al. Activity of the multitargeted antifolate LY231514 in the human tumor cloning assay. Cancer Chemother Pharmacol 44, 105–110 (1999). https://doi.org/10.1007/s002800050953
Issue Date:
DOI: https://doi.org/10.1007/s002800050953