Urinary Bladder Cancer Treatment

Several drugs have shown in vitro and in vivo pharmacological activity against urinary bladder cancer. This review aims at compiling the different drugs evaluated in in vitro and in vivo models of urinary bladder cancer and to review the advantages and limitations of both types of models, as well as the different methodologies applied for evaluating antineoplastic drug activity. Cancer is one of the most important public health issues and the most feared human disease (1). It is the second leading cause of death after coronary heart diseases and one in three persons suffers from cancer throughout their lives and one in four will die from this disease (2). Urinary bladder cancer is a common disease that ranks ninth in worldwide cancer incidence. It is the fourth most common cancer in men and the ninth in women, with a probability of developing in men three-times higher than in women, and with a ratio of 2:1 for caucasians and negros, respectively (3). The risk for developing this disease increases with age, with a peak between 60 and 70 years (4). Remarkable differences can be found in its incidence, it being predominately higher in developed countries such as in North America, Western and Southern Europe (5). In less industrialized countries, such as in Asia, Africa and the Middle East, the incidence of urinary bladder cancer is lower except for regions where Schistosoma haematobium is endemic. In these cases, urinary bladder squamous cell carcinoma is common (6). Involving exogenous and endogenous factors, the aetiology of urinary bladder cancer is multifactorial (Figure 1) (7, 8). Cigarette smoking, and environmental and occupational exposure to chemical agents remain the two major risk factors (7). Urinary bladder cancer is classified into three main types: transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma. At minor percentages are the small-cell tumours (1%) and sarcomatoid tumours (fewer than 1%) (9). Accounting for more than 90% of all cases, transitional cell carcinoma is the most common form of urinary bladder cancer (10). At diagnosis, nearly 70% of patients with urinary bladder cancer present with non-muscle-invasive lesions. Several clinical factors, such as tumour multiplicity, diameter, concomitant carcinoma in situ (CIS) and gender, have been identified as having prognostic significance for recurrence (11). CIS represents a major concern in the treatment of non-muscle-invasive lesions. CIS is a highgrade lesion that is characterized by disorderly proliferation of cells with marked cytological abnormalities (12). Although the European Association of Urology recommends transurethral resection and intra-vesical Bacillus CalmetteGuerin (BCG) immunotherapy for patients with CIS lesions, which achieves a complete response rate, 20% of patients will ultimately die of metastatic disease (12-14). The remaining 30% of patients at diagnosis have muscle-invasive lesions and 10% of these cases has a tendency to metastasize, with a poor prognosis (15). Urinary Bladder Cancer Treatment Treatment of non-muscle-invasive lesions. Complete transurethral resection is the standard treatment for nonmuscle-invasive lesions (16). Despite good prospects of survival (success rate of 80%), these tumours recur in approximately 70% of patients (10). One of the major challenges in treating non-muscle-invasive tumours is to reduce the high frequency of early recurrences, detected in more than 45% of the patients, three months following transurethral resection (17). In order to reduce the recurrence risk and to delay or prevent progression to a muscle-invasive lesion, after transurethral resection, adjuvant intra-vesical instillations of chemotherapy or 1273 Correspondence to: Paula A. Oliveira, Department of Veterinary Sciences, CECAV, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal. E-mail: [email protected]