title: Paclitaxel, ifosfamide, and nedaplatin as second-line treatment for patients with metastatic urothelial carcinoma: a phase II study of the SUOC group.
abstract: There is no standard second-line chemotherapy treatment for recurrent or metastatic urothelial cancer (MUC). The purpose of this phase II study was to evaluate the efficacy and toxicity of the three-drug combination of paclitaxel, ifosfamide, and nedaplatin (TIN). Patients with MUC were eligible after treatment failure with methotrexate, vinblastine, doxorubicin, and cisplatin, or gemcitabine and cisplatin. Doses for TIN therapy were paclitaxel 175 mg/m2 on day 1, ifosfamide 1500 mg/m2 on days 1-3, and nedaplatin 70 mg/m2 on day 1, every 4 weeks. Tumor response, the primary efficacy parameter, was assessed according to unidimensional measurements (Response Evaluation Criteria in Solid Tumors criteria, version 1.0). Secondary efficacy parameters were overall survival (OS) and progression-free survival (PFS). Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria, version 3.0. A total of 45 patients (13 females and 32 males) with MUC were evaluable for response and toxicity. The overall response rate was 40.0%. Median PFS time was 4.0 months (95% confidence interval [CI], 4.6-11.6). Median OS time was 8.9 months (95% CI, 10.5-18.9). Grade 3 or 4 hematologic adverse events were neutropenia (95.6%), anemia (15.6%), and thrombocytopenia (17.8%). The most common grade 3 or 4 non-hematologic adverse events were anorexia (4.4%) and elevated aspartate transaminase/alanine transaminase (2.2%). No toxic death was observed. The main limitation of this study is that only 10 patients (22.2%) who were previously treated with gemcitabine and cisplatin were included. In conclusion, TIN as second-line treatment for MUC is an active regimen with a manageable toxicity profile.
authors.affiliation: Department of Urology, School of Medicine, Sapporo Medical University, Sapporo Sapporo Medical University Urologic Oncology Consortium, Sapporo, Japan. hkitamu@sapmed.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taguchi
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Kunishima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yanase
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Shigyo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Mutoh
authors.forename: Fumimasa
authors.initials: F
authors.lastname: Fukuta
authors.forename: Naoya
authors.initials: N
authors.lastname: Masumori
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D007682:Kidney Pelvis; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014516:Ureteral Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D009944:Organoplatinum Compounds; C053989:nedaplatin; D017239:Paclitaxel; D007069:Ifosfamide