Randomized phase III trials of second-line chemotherapy in patients with advanced bladder cancer: progress and pitfalls — Ann Oncol

Ann Oncol (2011) 22 (2): 245-247.
doi: 10.1093/annonc/mdq684

Randomized phase III trials of second-line chemotherapy in patients with advanced bladder cancer: progress and pitfalls
J. Bellmunt1,*, T. K. Choueiri2, F. A. B. Schutz2 and J. E. Rosenberg2


+ Author Affiliations
1Department of Medical Oncology, University Hospital del Mar, Institut Municipal d'Investigació Mèdica, Barcelona, Spain
2Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA
*E-mail: joaquim.bellmunt@gmail.com)


Few randomized clinical trials have been conducted in first-line setting and even fewer in the second-line setting in advanced bladder cancer. Overall, patients' impaired renal function, poor performance status (PS), advanced age and comorbidities have limited trial design and feasibility. In addition to the difficulty accruing patients on such trials, several methodological issues related to patient and disease heterogeneity have limited the interpretation of phase II and even phase III trials [ 1].

The second-line bladder cancer trial reported by Albers et al. [ 2] in the present issue of Annals of Oncology merits the attention for being the second randomized trial after the publication of the vinflunine phase III trial [ 3] and for providing new information in this area. Patients failing first-line chemotherapy were randomized to a short- or long-term gemcitabine and paclitaxel (GP) combination. Although it was described as a phase III study, due to its sample size, in reality it should be considered in the realm of a randomized phase II design.

Taken together these two trials provide several key concepts and definitions that need to be considered when designing new trials and interpreting results in the second-line setting. These include (i) the definition of second-line therapy; (ii) the analysis based on eligibility versus intention to treat (ITT); (iii) the need for clear definitions of primary refractory disease, acquired resistant disease and recurrent disease after treatment; (iv) the use of prognostic factors for proper stratification; (v) the value of rechallenging with agents already used in first-line therapy and (vi) the role of prolonged/maintenance treatment in second-line versus a predefined period.

The definition of second-line therapy: Eligibility criteria for second-line phase II trials have been variable and sometimes confusing, limiting the interpretation and comparison of outcomes across studies. Therefore, a strict definition of …

Randomized phase III trials of second-line chemotherapy in patients with advanced bladder cancer: progress and pitfalls — Ann Oncol