Background: Several single chemotherapeutic agents have been evaluated as the second-line
treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often
led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular
population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the
previous toxicity of chemotherapy.
Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and
safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable
patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for
advanced or metastatic disease.
Results: The study was prematurely closed due to two sudden deaths that were judged by the review
board as treatment-related. Only ten patients were evaluated and received at least one cycle of
vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis
(mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with
median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67-
4.73). There were three serious adverse events namely two sudden deaths and one grade 4
thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events
were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in
30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic
Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its
safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a
single institute experience in a limited number of patients.