title: Third-Line Chemotherapy for Metastatic Urothelial Cancer: A Retrospective Observational Study.
abstract: The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting.We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma.Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10-17) and 31 (28-36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13-22) and an OS of 38 (33-41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20-0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95-9.77; P < 0.01).We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines of treatment, as it may yield a survival benefit with low costs and no detrimental effects on quality of life.
authors.affiliation: From the Medical Oncology, University Federico II of Naples, Naples (GDL, CB, DR, SDP); Medical Oncology, Hospital "San Luca," Vallo della Lucania, Salerno (TB); ASL Napoli 3 SUD, Naples (CR); Istituto Oncologico del Sud, Naples (VM); Division of Urology, European Institute of Oncology, Milan (MF, ODC); Division of Urology, Hospital "San Luca," Vallo della Lucania, Salerno (AB); Department of Emergency and Organ Transplantation, Urology and Kidney Transplantation Unit, University of Bari, Bari, Italy (GL); Department of Urology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (ODC); and Department of Medicine, Section of Hematology-Oncology, University of Alabama, Birmingham School of Medicine, Birmingham, AL (GS).
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.forename: Carlo
authors.initials: C
authors.lastname: Buonerba
authors.forename: Teresa
authors.initials: T
authors.lastname: Bellelli
authors.forename: Concetta
authors.initials: C
authors.lastname: Romano
authors.forename: Vittorino
authors.initials: V
authors.lastname: Montanaro
authors.forename: Matteo
authors.initials: M
authors.lastname: Ferro
authors.forename: Alfonso
authors.initials: A
authors.lastname: Benincasa
authors.forename: Dario
authors.initials: D
authors.lastname: Ribera
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lucarelli
authors.forename: Ottavio
authors.initials: O
authors.lastname: De Cobelli
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D006454:Hemoglobins; D006801:Humans; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011788:Quality of Life; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods* / Q000401:mortality; D012709:Serum Albumin; D013997:Time Factors; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*
chemical_list: D006454:Hemoglobins; D012709:Serum Albumin; D003520:Cyclophosphamide