title: A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen.
abstract: A multicentre phase II trial to determine the efficacy of vinflunine as second-line therapy in patients with advanced transitional cell carcinoma (TCC) of the bladder; secondary objectives were to assess duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients had tumours that failed or progressed after first-line platinum-containing regimens for advanced or metastatic disease, or had progressive disease after platinum-containing chemotherapy given with adjuvant or neoadjuvant intent. Response and adverse events were assessed according to WHO criteria and NCI-CTC (version 2), respectively. Out of 51 patients treated with 320 mg m(-2) of vinflunine, nine patients responded to the therapy yielding an overall response rate of 18% (95% CI: 8.4-30.9%), and 67% (95%CI: 52.1-79.3%) achieved disease control (PR+SD). Of note, responses were seen in patients with relatively poor prognostic factors such as a short (<12 months) interval from prior platinum therapy (19%, including an 11% response rate in those progressing <3 months after platinum treatment), prior treatment for metastatic disease (24%), prior treatment with vinca alkaloids (14%) and visceral involvement (20%). The median duration of response was 9.1 months (95% CI: 4.2-15.0) and the median PFS was 3.0 months (95% CI: 2.4-3.8). The median OS was 6.6 months (95% CI: 4.8-7.6). The main haematological toxicity was grade 3-4 neutropenia, observed in 67% of patients (42% of cycles). Febrile neutropenia was observed in five patients (10%) and among them two were fatal. Constipation was frequently observed (but was manageable and noncumulative) and was grade 3-4 in only 8% of patients. The incidence of grade 3 nausea and vomiting was very low (4 and 6% of patients, respectively). Neither grade 3-4 sensory neuropathy nor severe venous irritation was observed. Moreover, and of importance in this particular study population, no grade 3-4 renal function impairment was observed. Vinflunine is an active agent for the treatment of platinum-pretreated bladder cancer, and these results warrant further investigation in phase III trials, either as monotherapy or in combination with other agents as treatment of advanced/metastatic TCC of the bladder.
authors.affiliation: CRLC Val d'Aurelle, Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Culine
authors.forename: C
authors.initials: C
authors.lastname: Theodore
authors.forename: M
authors.initials: M
authors.lastname: De Santis
authors.forename: B
authors.initials: B
authors.lastname: Bui
authors.forename: T
authors.initials: T
authors.lastname: Demkow
authors.forename: J
authors.initials: J
authors.lastname: Lorenz
authors.forename: F
authors.initials: F
authors.lastname: Rolland
authors.forename: F-M
authors.initials: FM
authors.lastname: Delgado
authors.forename: B
authors.initials: B
authors.lastname: Longerey
authors.forename: N
authors.initials: N
authors.lastname: James
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; C111217:vinflunine; D014747:Vinblastine