Second-line therapy in bladder cancer.

PURPOSE OF REVIEW: To review new developments in second-line treatment for transitional cell carcinoma of the urinary bladder focusing on advances and findings within the last year. RECENT FINDINGS: So far no standard therapy has been established for pretreated patients with transitional cell carcinoma. Prognostic and predictive factors for response and outcome in pretreated patients have been studied retrospectively and will help to identify those who might benefit from intensive therapy and those who would rather improve their quality of life with best supportive care. Single-agent chemotherapy in this setting provided low response rates, short progression-free and overall survival. Vinflunine, a novel vinca-alkaloid, and best supportive care had a modest, but still significant benefit at a very moderate toxicity rate in a randomized phase III trial. As for second-line combination chemotherapy, response rates as well as potential toxicities are higher and the progression-free survival and overall survival benefits are still poorly understood. New chemotherapeutics and approaches like metronomic chemotherapy and novel agents are under investigation. SUMMARY: With vinflunine there is reasonable hope for a new standard chemotherapy in second-line management of transitional cell carcinoma. However, due to the reported results with single agents and combination chemotherapy, treatment within clinical trials is still the best choice in patients progressing after first-line chemotherapy.

[Organization, administration, and performance of clinical studies]. / Organisation, Administration und Durchfuhrung von klinischen Studien.

This contribution deals with all important organizational and administrative aspects of clinical studies in German speaking countries. All trials are to be executed in accordance with the Good Clinical Practice (GCP) Guidelines. GCP applies to the process of designing, conducting, recording, and reporting of clinical studies. Compliance with GCP facilitates the mutual acceptance of resulting clinical data by the respective regulatory authorities worldwide. Before initiating a clinical study the investigator has to obtain written and dated approval from the responsible ethics committee, the competent authorities, and the hospital administration. The investigator's study file contains all essential study documents. One of the most important tasks of an investigator is to properly inform the prospective subjects and to obtain their informed consent. All relevant treatment-related information has to be recorded in the patient files. These source data are transferred to case report forms. During monitoring visits, audits, and inspections, source data verification will be performed routinely. Any adverse events (AEs) must be documented according to the CTCAE, the Common Terminology Criteria for Adverse Events. All serious adverse events (SAEs) have to be reported to the sponsor immediately. At the end of the study a termination visit is performed, and all authorities are officially informed about the termination of the trial.

Vinflunine in the treatment of bladder cancer.

Vinflunine (VFL) is a third-generation bifluorinated semi-synthetic vinca alkaloid obtained by superacidic chemistry from its parent compound, vinorelbine. As with the other vinca alkaloids, the main antineoplastic effects of VFL arise from its interaction with tubulin, the major component of microtubules in mitotic spindles. In contrast to other vinca alkaloids, VFL shows some distinctive properties in terms of tubulin binding, possibly explaining its superior antitumor activity in vitro and in vivo compared with vinorelbine as well as its excellent safety profile. In transitional cell carcinoma (TCC), two single-agent phase II trials were performed testing VFL in platinum-pretreated patients, showing moderate response rates and promising disease control rates. Therefore, the first phase III trial in modern times for second-line TCC of the urothelium was designed in order to further investigate the activity of VFL. First results were presented at the 2008 ASCO conference. VFL appears to be a possible treatment option for patients with TCC progressing after first-line platinum-containing chemotherapy.

New developments in first- and second-line chemotherapy for transitional cell, squamous cell and adenocarcinoma of the bladder.

PURPOSE OF REVIEW: To review the systemic treatment, patient selection and treatment outcome of transitional cell carcinoma of the urinary bladder, squamous cell carcinoma and adenocarcinoma, focusing on advances and findings within the last year. RECENT FINDINGS: Cisplatin-based chemotherapy is considered to be the standard treatment for transitional cell carcinoma. In recent updates of randomized trials, patients with favorable prognostic factors were shown to have a chance of long-term disease-free survival even after chemotherapy for metastatic disease. Patient selection for cisplatin, newer drugs or alternative combinations is crucial. New genetic markers like excision repair cross-complementing 1 expression were developed and tested for this purpose. Adequate evaluation of renal function plays an important role for treatment selection, especially in the elderly population. Newer chemotherapeutics like oxaliplatin, vinflunine and pemetrexed have been studied in the first- or second-line settings. Their efficacy is promising, but there is still a need for further testing. Only few data are available on the systemic treatment of squamous cell carcinoma and adenocarcinoma. Complete resection seems to be more important than chemotherapy in the rare cases of adenocarcinoma of the urinary tract. SUMMARY: In locally advanced and metastatic disease patient- and tumor-related prognostic factors and predictive factors for response to treatment will guide treatment decisions in the future.