Chemosensitivity Testing of Gynecologic Tumors to Chemotherapeutic Agents by the Subrenal Capsule Tumor Implant Assay

Abstract

Subrenal capsule assay (SRCA) is a promising method of "in vivo" chemosensitivity test. We planned the laboratory procedure of SRCA in order to make an animal model of in vivo chemosensitivity test which can be used for the gynecologic cancers. The 6-day subrenal capsule assays were performed with several gynecologic malignancies. Fresh tumor fragments of cervical cancer, ovarian cancer, endometrial cancer, sarcoma, and choriocarcinoma were implanted as 1 X 1 X 1 mm fragments under the renal capsule of immunocompetent female adult mice and tested against several chemotherapeutic drugs or their combinations, In this study, we could show the variations in growth rates of the xenografts under the renal capsule. This fact seems to reflect the differences of the growth potentials as well as the heterogeneity of the cell population comprising each human tumor. An average of 69.3% of tumors showed positive growth and 10.6% demonstrated no measurable change, but 20.0% showed partial regression in size. The evaluable assay rate of this study was over 90.5%. The response rates of 19 cervical carcinomas, 2 ovarian carcinomas, 1 endometrial carcinoma, 1 sarcoma, and 1 choriocarcinoma to several chemotherapeutic agents and their combinations were determined. Response rates varied from 0% (0/3) to adriamycin to 85.7% (617) to epirubicin plus cis-platin in cervical carcinoma (cf: 75.0% (9/12) to cis-platin, 42.9% (317) to cyclophosphamide, 40.0% (4/10) to 5-fluorouracil, and 66.7% (4/6) to bleomycin). A total of 13 clinical correlations of SRCA with clinical outcome were possible in the prospective study, and the overall predictive accuracy of the SRCA in our study was 84.6%. The SRCA is considered as a reliable in vivo clinical test to predict the effectiveness of drugs against a tumor in an individual patient.