Activity of the multitargeted antifolate LY231514 in the human tumor cloning assay

被引:47
作者
Britten, CD
Izbicka, E
Hilsenbeck, S
Lawrence, R
Davidson, K
Cerna, C
Gomez, L
Rowinsky, EK
Weitman, S
Von Hoff, DD
机构
[1] Canc Therapy & Res Ctr S Texas, Inst Drug DEv, Grossman Canc Ctr, San Antonio, TX 78229 USA
[2] Univ Texas San Antonio, San Antonio, TX 78229 USA
关键词
human tumor cloning assay; LY231514; multitargeted antifolate;
D O I
10.1007/s002800050953
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: This study was performed to evaluate the activity of the multitargeted antifolate (RITA 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 mu g/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 mu g/ml, 11% (17/148) at 1.0 mu g/ml, and 23% (33/141) at 10 mu g/ml. In this range of concentrations achievable clinically, there was a significant concentration-response relationship. At 10 mu g/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.
引用
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页码:105 / 110
页数:6
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