Responsiveness of human lung cancer/nude mouse to antitumor agents in a model using clinically equivalent doses

Abstract

The responses of 14 lines of human lung cancer xenografts in BALB/c-nu/nu mice to eight known antitumor agents were investigated. These xenografts consisted of four small-cell carcinomas (SCLC) and ten non-small-cell carcinomas (four large cell, three squamous cell, and three adenocarcinomas; NSCLC). The doses used in the experiments were the maximum tolerated dose (MTD) in nude mice and the "rational dose" (RD), the latter considered to be pharmacokinetically equivalent to the clinical dose. When given at MTDs, all drugs except 5-fluorouracil (5-FU) and methotrexate (MTX) were extremely effective against NSCLC as well as SCLC. The response rates of drug-sensitive SCLC to mitomycin C (MMC), ACNU, and vinblastine (VLB) were 100%, and those to Adriamycin (ADR) and vincristine (VCR) were 75%. In addition, the response rates of even drug-resistant NSCLC to MMC and VLB were 70% and 90%, respectively. In contrast, the response rates of NSCLC to RDs of the drugs were reduced to less than 40% and corresponded well to the respective clinical rates. In SCLC, a good correlation of experimental and clinical response rates was observed with four drugs [cyclophosphamide (CPM), ACNU, VLB, and 5-FU]. As a result, we emphasize that a more reasonable prediction of the clinical effectiveness of antitumor agents can be made by a protocol using clinically equivalent doses.