CAMPTOTHECIN ANALOGUES/CISPLASTIN: AN EFFECTIVE TREATMENT OF ADVANCED BLADDER CANCER IN A PRECLINICAL IN VIVO MODEL SYSTEM

Abstract

Objective To evaluate the impact of the camptothecin analogs on human TCC xenograft, both as monotherapy and in combination with cisplatin (CDDP). Materials and Methods Human transitional cell carcinoma (TCC) xenograft tumor line (DU4184) tested by subrenal capsule assay in 112 nude mice(NM-SRCA). CDDP and the camptothecin analogs irinotecan (CPT-11) and 9-aminocamptothecin(9-AC) were evaluated. Results Both of the camptothecin analogs showed significant short term tumor inhibition which translated into enhanced survival. Maximal tumor inhibition (>95%) was achieved when either of the camptothecin analogs was combined with CDDP with minimal host toxicity. This translated into 400% increase in median survival. While all controls were dead 39 days following tumor implantation, none of the combination treated animals had died. Conclusion The combination of CDDP with these camptothecin analogs is an effective therapy against this model of advanced TCC. These observations suggest potential clinical value.