The subrenal capsule assay (SRC) is an vivo test of human tumor responsiveness to drug therapy (see Appendix 1 for illustration of assay). This grant is requested to develop and verify the SRC as a test for determining the chemosensitivity of human tumors. This study will be a stepwise systematic approach which will complete the following tasks: 1. Develop the SRC in immunosuppressed conventional mice. An effective, well-tolerated immunosuppressive regimen will be developed which will result in the persistence and long term growth of human tumors under the kidney capsule of conventional mice. This will provide an environment for the study of the growth and function of human tumors and will permit an evaluation of rapid as well as more protracted effects of chemotherapeutic agents against these tumors. 2. Determine a method of storing human tumor pieces which maintains their original growth properties and chemosensitivity as defined in the SRC. 3. In a preclinical study verify the reliability of the SRC for predicting the effectiveness of single agent and combination chemotherapy. This will be accomplished by comparing the growth inhibitory effect of individual chemotherapeutic agents against mouse tumors xenografted under the kidney capsule of rats to the effect of these agents against the mouse tumor growing in the subcutaneous tissue of its syngeneic host. Based on single agent activity, combinations of drugs will be derived and tested in the above systems. 4. In a clinical study verify the reliability of the SRC for predicting the effectiveness of single agent and combination chemotherapy. This will be accomplished by carrying out tow randomized, prospective, crossover two-arm clinical trials; one in previously untreated patients with advanced measurable colon cancer comparing the therapeutic efficacy of 5-fluorouracil (standard chemotherapy) to SRC-predicted single agent chemotherapy; the other in previously untreated patients with advanced measurable non-small cell lung cancer comparing the therapeutic efficacy of standard combination chemotherapy to SRC-predicted combination chemotherapy.
| Parnes, S M; Bennett, J A; Deconti, R C et al. (1989) Accuracy of the subrenal capsule xenograft assay in predicting the clinical growth and chemosensitivity of human squamous head and neck carcinomas. J Surg Oncol 42:21-7 |
| Bennett, J A; Parnes, S M; DeConti, R C (1989) Growth and chemosensitivity of human head and neck cancers implanted under the kidney capsule of cyclosporine-immunosuppressed mice. Ann Otol Rhinol Laryngol 98:455-60 |
| Bennett, J A; Pilon, V A; Briggs, D R et al. (1985) Evaluation of cyclosporine-treated mice as hosts for growing and testing the chemosensitivity of first-transplant-generation human tumor xenografts implanted under the kidney capsule. J Natl Cancer Inst 75:925-36 |
| Bennett, J A; Pilon, V A; MacDowell, R T (1985) Evaluation of growth and histology of human tumor xenografts implanted under the renal capsule of immunocompetent and immunodeficient mice. Cancer Res 45:4963-9 |
