Guru Sonpavde1, Gregory R Pond2, Toni K Choueiri3, Stephanie Mullane3, Guenter Niegisch4, Peter Albers4, Andrea Necchi5, Giuseppe Di Lorenzo6, Carlo Buonerba7, Antonio Rozzi8, Kazumasa Matsumoto9, Jae-Lyun Lee10, Hiroshi Kitamura11, Haruki Kume12, Joaquim Bellmunt3. 1. UAB Comprehensive Cancer Center, Birmingham, AL, USA. Electronic address: gsonpavde@uabmc.edu. 2. McMaster University, Ontario, Canada. 3. Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. 4. Heinrich Heine University, Dusseldorf, Germany. 5. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 6. University Federico II, Naples, Italy. 7. Centro di Riferimento Oncologico della Basilicata IRCCS, Rionero In Vulture, Italy. 8. Istituto Neurotraumatologico Italiano, Grottaferrata, Italy. 9. Kitasato University School of Medicine, Sagamihara, Japan. 10. Asan Medical Center, Seoul, Republic of Korea. 11. Sapporo Medical University School of Medicine, Sapporo, Japan. 12. University of Tokyo Hospital, Tokyo, Japan.
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.
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-freepaclitaxel (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.
Authors: Andrea Necchi; Salvatore Lo Vullo; Luigi Mariani; Daniele Raggi; Patrizia Giannatempo; Giuseppina Calareso; Elena Togliardi; Flavio Crippa; Nicola Di Genova; Federica Perrone; Maurizio Colecchia; Biagio Paolini; Giuseppe Pelosi; Nicola Nicolai; Giuseppe Procopio; Roberto Salvioni; Filippo G De Braud Journal: Invest New Drugs Date: 2016-02-12 Impact factor: 3.850
Authors: Kamran Zargar-Shoshtari; Michael Kongnyuy; Pranav Sharma; Mayer N Fishman; Scott M Gilbert; Michael A Poch; Julio M Pow-Sang; Philippe E Spiess; Jingsong Zhang; Wade J Sexton Journal: World J Urol Date: 2016-04-12 Impact factor: 4.226
Authors: Thomas Seisen; Asha Jamzadeh; Jeffrey J Leow; Morgan Rouprêt; Alexander P Cole; Stuart R Lipsitz; Adam S Kibel; Paul L Nguyen; Maxine Sun; Mani Menon; Joaquim Bellmunt; Toni K Choueiri; Quoc-Dien Trinh Journal: JAMA Oncol Date: 2018-02-01 Impact factor: 31.777
Authors: Giuseppe Di Lorenzo; Carlo Buonerba; Teresa Bellelli; Concetta Romano; Vittorino Montanaro; Matteo Ferro; Alfonso Benincasa; Dario Ribera; Giuseppe Lucarelli; Ottavio De Cobelli; Guru Sonpavde; Sabino De Placido Journal: Medicine (Baltimore) Date: 2015-12 Impact factor: 1.817