Experimental and clinical studies on the treatment of lung cancer.Part 1: Drug screening and combination chemotherapy using advanced Lewis lung carcinoma as a model of human lung cancer.

Lewis lung carcinoma in an advanced stage was evaluated as a model of human lung cancer for screening drugs and drug combinations. The tumor was fairly resistant to drugs when therapy was started 7 days after tumor transplantation. Among the drugs which have been used conventionally in the treatment of human lung cancer, cyclophosphamide was the only are distinctly active against the tumor. BCNU, a nitrosourea, was fairly active; however, adriamycin, methotrexate and vincristine were only marginally active. The drug sensitivity of the experimental tumor in an advanced stage appeared to correlate well with that of human lung cancer, especially in the case of non-small cell lung cancer, which is regarded as a representative of drug-resistant human tumors. As for the screening of new drugs, ifosfamide, an analogue of cyclophosphamide, was as equally active as the mother compound. ACNU, a new nitrosourea, was more effective than the mother compound, BCNU. These drugs have proved to be active against human lung cancer, indicating that the advanced Lewis lung carcinoma provided a drug activity spectrum closely analogous to human lung cancer. However, in the case of cis-dichlorodiammineplatinum (Ⅱ), a considerable dissociation was observed between the animal model and human lung cancer: the drug, which was regarded to be inactive in the animal model, has recently shown clinical activity against small cell and non-small cell lung cancer. The effect of drug combinations was distinct only in the case of cyclophosphamide plus ACNU, or ifosfamide plus ACNU, suggesting the usefulness of these drug combinations in the treatment of human lung cancer.