SALVAGE CHEMOTHERAPY FOR BLADDER CANCER

Eur Urol. 2015 Aug 8. pii: S0302-2838(15)00701-0. doi: 10.1016/j.eururo.2015.07.042. [Epub ahead of print]

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

Sonpavde G1, Pond GR2, Choueiri TK3, Mullane S3, Niegisch G4, Albers P4, Necchi A5, Di Lorenzo G6, Buonerba C7, Rozzi A8, Matsumoto K9, Lee JL10, Kitamura H11, Kume H12, Bellmunt J3.

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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.