TY - JOUR
T1 - Incomplete cross-resistance between taxanes for advanced urothelial carcinoma
T2 - Implications for clinical practice and trial design
AU - Sonpavde, Guru
AU - Pond, Gregory R.
AU - Mullane, Stephanie
AU - Qu, Angela Q.
AU - Di Lorenzo, Giuseppe
AU - Federico, Piera
AU - Necchi, Andrea
AU - Rosenberg, Jonathan E.
AU - Bellmunt, Joaquim
AU - Choueiri, Toni K.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Abstract 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.
AB - Abstract 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.
KW - Docetaxel
KW - Paclitaxel
KW - Prognosis
KW - Salvage therapy
KW - Urothelial carcinoma
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U2 - 10.1016/j.clgc.2014.10.005
DO - 10.1016/j.clgc.2014.10.005
M3 - Article
C2 - 25481485
AN - SCOPUS:84929077299
VL - 13
SP - 250
EP - 256
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
SN - 1558-7673
IS - 3
M1 - 335
ER -