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


METHODS
Individual patient-level data from phase 2 trials of salvage systemic therapy were used.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.


RESULTS
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.
UAB Comprehensive Cancer Center, Birmingham, AL, USA. Electronic address: gsonpavde@uabmc.edu.
Guru
G
Sonpavde
McMaster University, Ontario, Canada.
Gregory R
GR
Pond
Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Toni K
TK
Choueiri
Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Stephanie
S
Mullane
Heinrich Heine University, Dusseldorf, Germany.
Guenter
G
Niegisch
Heinrich Heine University, Dusseldorf, Germany.
Peter
P
Albers
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Andrea
A
Necchi
University Federico II, Naples, Italy.
Giuseppe
G
Di Lorenzo
Centro di Riferimento Oncologico della Basilicata IRCCS, Rionero In Vulture, Italy.
Carlo
C
Buonerba
Istituto Neurotraumatologico Italiano, Grottaferrata, Italy.
Antonio
A
Rozzi
Kitasato University School of Medicine, Sagamihara, Japan.
Kazumasa
K
Matsumoto
Asan Medical Center, Seoul, Republic of Korea.
Jae-Lyun
JL
Lee
Sapporo Medical University School of Medicine, Sapporo, Japan.
Hiroshi
H
Kitamura
University of Tokyo Hospital, Tokyo, Japan.
Haruki
H
Kume
Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Joaquim
J
Bellmunt
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology
D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel
Advanced urothelial carcinoma; Combination; Salvage; Survival; chemotherapy