Incomplete Cross-Resistance Between Taxanes for Advanced Urothelial Carcinoma: Implications for Clinical Practice and Trial Design

In this retrospective study, docetaxel treatment after previous paclitaxel treatment and the reverse sequence demonstrated outcomes and activity similar to salvage therapy for advanced urothelial carcinoma (UC). The clinical implications are that trials using a taxane can probably allow previous exposure to a different taxane, and patients treated off protocol may receive a taxane after previous exposure to a different taxane. Background: Taxanes such as paclitaxel and docetaxel are commonly used for second-or third-line salvage systemic therapy for metastatic UC. Although trials have generally excluded previous exposure to taxanes when using a taxane in a salvage therapy trial, taxanes might not be completely cross-resistant. Hence, we aimed to study outcomes with docetaxel after previous paclitaxel and the reverse sequence, to identify the level of cross-resistance between these taxanes. Patients and Methods: Data from a randomized phase II trial that compared salvage therapy with docetaxel combined with either placebo or vandetanib for advanced UC were analyzed. Both arms were combined for analysis because no differences in any outcomes were observed. Data were also requested from institutions for patients who received paclitaxel after previous docetaxel treatment. Descriptive statistics were used to summarize patient and treatment characteristics and outcomes. The primary clinical end point of interest was overall survival (OS). Results: Of 148 patients who received docetaxel with either vandetanib or placebo, 21 had received previous paclitaxel treatment. No difference in OS, progression-free survival, or response rate was observed with docetaxel based on previous paclitaxel treatment after adjusting for known prognostic factors. Among the 8 patients who received paclitaxel after previous docetaxel treatment, partial response was observed in 1 patient (12.5%) and stable disease in 2 patients (25%). Conclusion: Docetaxel treatment after previous paclitaxel treatment and the reverse sequence demonstrates activity in advanced UC. There is no strong evidence to disallow patients with previous exposure to a taxane to enroll in a clinical trial involving another taxane. (C) 2015 Elsevier Inc. All rights reserved.