Abstract
BackgroundSingle-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma (UC). ObjectiveTo study the impact of combination chemotherapy delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy. Design, setting, and participantsIndividual patient-level data from phase 2 trials of salvage systemic therapy were used. InterventionsTrials 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 analysisInformation 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 limitationsData 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. ConclusionsPatients 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 summaryThis 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.
Published Version
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