Efficacy and Safety of Gemcitabine Plus Either Taxane or Carboplatin in the First-Line Setting of Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis.
Although gemcitabine plus carboplatin (GCa) is the conventional first-line chemotherapy for cisplatin-ineligible metastatic urothelial carcinoma, its results are suboptimal. A meta-analysis evaluated the results of gemcitabine with either carboplatin or a taxane (GT). Literature was searched for studies including GT (paclitaxel or docetaxel) and GCa. We pooled trial level data including response-rate, progression-free survival, overall survival (OS), and Grade 3 to 4 side effects. Trial characteristics and outcomes were univariably compared between GT and GCa. Those factors, which were recorded in > 12 trials, were analyzed. Multivariable regression models were used adjusting for Eastern Cooperative Oncology Group performance status 2 and the presence of visceral metastases. Each trial was weighted by its sample size. Twenty-seven arms of trials totaling 1032 patients were selected, of which 13 contained GT (n = 484) and 14 GCa (n = 548). The percentage of patients with Eastern Cooperative Oncology Group performance status 2 was statistically significantly different between the 2 groups (median, 8.7% vs. 23.9%; P = .003). No efficacy outcome was statistically significantly different. Median OS was 13.2 months (range, 10-15.8 months) for GT and 10 months (range, 3.3-20 months) for GCa (P = .12). However, statistically significant increases in the frequency of Grade 3 to 4 anemia (P = .010) and thrombocytopenia (P = .010) for GCa, and neuropathy (P = .040) for GT were observed. No difference in OS according to treatment was found multivariably (P = .79). In this analysis, a similar response rate and survival and worse neurotoxicity were observed with GT compared with GCa, for which hematologic toxicity was more frequent. GT is an alternative to GCa for advanced cisplatin-ineligible urothelial cancer.
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: andrea.necchi@istitutotumori.mi.it.
Andrea
A
Necchi
McMaster University, Hamilton, Ontario, Canada.
Gregory R
GR
Pond
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Daniele
D
Raggi
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Patrizia
P
Giannatempo
Developmental Therapeutics Committee and Co-Chair of the Genitourinary Committee, US Oncology Research, Comprehensive Centers of Nevada, Las Vegas, NV.
Nicholas J
NJ
Vogelzang
Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
Petros
P
Grivas
Genitourinary Medical Oncology, Mount Sinai School of Medicine, Tisch Cancer Institute, New York, NY.
Matthew D
MD
Galsky
Bladder Cancer Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
Joaquim
J
Bellmunt
Medical Oncology and Hematology, UAB Comprehensive Cancer Center, Birmingham, AL.
Guru
G
Sonpavde
D000970:Antineoplastic Agents / Q000009:adverse effects; D016190:Carboplatin / Q000009:adverse effects*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D043823:Taxoids / Q000009:adverse effects*; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D043823:Taxoids; D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine
First-line therapy; Meta-analysis; Systemic therapy; Taxanes; Urothelial carcinoma