Single-agent taxane versus taxane-containing combination chemotherapy as salvage therapy for advanced urothelial Carcinoma

Guru Sonpavde, Gregory R. Pond, Toni K. Choueiri, Stephanie Mullane, Guenter Niegisch, Peter Albers, Andrea Necchi, Giuseppe Di Lorenzo, Carlo Buonerba, Antonio Rozzi, Kazumasa Matsumoto, Jae Lyun Lee, Hiroshi Kitamura, Haruki Kume, Joaquim Bellmunt

Research output: Contribution to journalArticlepeer-review

Abstract

Background Single-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma (UC). Objective To study the impact of combination chemotherapy delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy. Design, setting, and participants Individual patient-level data from phase 2 trials of salvage systemic therapy were used. Interventions Trials evaluating either single agents (paclitaxel or docetaxel) or combination chemotherapy (taxane plus one other chemotherapeutic agent or more) following prior platinum-based therapy were used. Outcome measurements and statistical analysis Information regarding the known major baseline prognostic factors was required: time from prior chemotherapy, hemoglobin, performance status, albumin, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of prognostic factors and combination versus single-agent chemotherapy with overall survival (OS). Results and limitations Data were available from eight trials including 370 patients; two trials (n = 109) evaluated single-agent chemotherapy with docetaxel (n = 72) and cremophor-free paclitaxel (n = 37), and six trials (n = 261) evaluated combination chemotherapy with gemcitabine-paclitaxel (two trials, with n = 99 and n = 24), paclitaxel-cyclophosphamide (n = 32), paclitaxel-ifosfamide-nedaplatin (n = 45), docetaxel-ifosfamide-cisplatin (n = 26), and paclitaxel-epirubicin (n = 35). On multivariable analysis after adjustment for baseline prognostic factors, combination chemotherapy was independently and significantly associated with improved OS (hazard ratio: 0.60; 95% confidence interval, 0.45-0.82; p = 0.001). The retrospective design of this analysis and the trial-eligible population were inherent limitations. Conclusions Patients enrolled in trials of combination chemotherapy exhibited improved OS compared with patients enrolled in trials of single-agent chemotherapy as salvage therapy for advanced UC. Prospective randomized trials are required to validate a potential role for rational and tolerable combination chemotherapeutic regimens for the salvage therapy of advanced UC. Patient summary This retrospective study suggests that a combination of chemotherapy agents may extend survival compared with single-agent chemotherapy in selected patients with metastatic urothelial cancer progressing after prior chemotherapy.

Original languageEnglish
Pages (from-to)634-641
Number of pages8
JournalEuropean Urology
Volume69
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Keywords

  • Advanced urothelial carcinoma
  • chemotherapy
  • Combination
  • Salvage
  • Survival

ASJC Scopus subject areas

  • Urology

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