Single-agent Taxane Versus Taxane-containing Combination Chemotherapy as Salvage Therapy for Advanced Urothelial Carcinoma. Academic Article uri icon

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  • 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.


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

publication date

  • April 2016

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