Novel therapeutics in the treatment of bladder cancer

Department of Urology, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA.
Current Opinion in Urology (Impact Factor: 2.33). 10/2004; 14(5):287-93. DOI: 10.1097/00042307-200409000-00007
Source: PubMed


The successful treatment of bladder cancer remains a challenge for urologists and oncologists. There have been substantial changes in the therapeutic options for the management of both superficial and muscle-invasive bladder cancer in the last 5 years. Here we review the preclinical and clinical developments over the last year in bladder cancer therapeutics.
There is a growing trend toward the use of multimodal treatments for all bladder cancers. For superficial disease, intravesical instillation of chemotherapeutic agents after transurethral resection is quickly becoming the standard of care. Novel therapeutic modalities under investigation include DNA vaccines, magnetically targeted carriers, bio-adhesive microspheres and antisense oligodeoxynucleotides. For muscle-invasive bladder cancer, systemic perioperative chemotherapy is being used with increasing frequency and the latest preclinical research efforts are focused on the inhibition of angiogenesis and other processes predisposing to metastatic disease.
Treatment goals for bladder cancer of any stage are complete removal of the initial tumor, prevention of disease recurrence and effective inhibition of progression to advanced disease with the ultimate aim of reducing mortality. The myriad novel therapeutic modalities currently being explored suggest that these goals may perhaps be achievable within our lifetime.

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    • "Immunotherapy with bacillus Calmette-Gué rin (BCG) remains the most effective form of intravesical therapy for prophylaxis of recurrence [2] and progression [3] [4] in superficial bladder cancer. "
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    ABSTRACT: This paper reviews the most relevant findings published recently on intravesical chemotherapy for superficial bladder tumours and provides recommendations based on documented research. The evidence was categorised according to the North of England Evidence Based Guideline Development Project. Levels of evidence were based on the source of the information, meta-analyses, systematic reviews, well-designed randomised or nonrandomised controlled clinical trials, and uncontrolled studies or consensus. Three levels of recommendations were assigned to the evidence obtained. Despite intravesical chemotherapy being used prophylactically after endoscopic resection of superficial bladder tumours, the recurrence rate is still 36-44%. Researchers have focused on improving the effectiveness of intravesical chemotherapy, each adopting a different strategy. Some have aimed to identify the optimum timing for instillations and others to improve the pharmacokinetics of agents by avoiding their dilution, increasing their stability, or improving the absorption of the drug by bladder mucosa. Some researchers are looking into new, single chemotherapeutic agents or combinations for intravesical use and others into avoiding chemoresistance with resistance-reverting agents (modulating agents) or by using in vitro chemosensitivity tests to identify the most sensitive drug. Progress has been made in optimising intravesical chemotherapy for timing of instillations and pharmacokinetic interventions. Simple and inexpensive approaches may have a widespread, practical acceptance by urologists, but it is more difficult to extend new techniques requiring more complex and sometimes expensive instrumentation to the urologic community. Further research into finding more effective cytotoxic drugs, combinations, or modulating agents should be encouraged.
    European Urology 09/2006; 50(2):225-34. DOI:10.1016/j.eururo.2006.05.035 · 13.94 Impact Factor
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    ABSTRACT: Bladder cancer is the second most common genitourinary cancer and is a significant cause of morbidity and mortality with an estimated 63210 new cases and projected 13180 deaths in 2005 in the USA (1). This malignancy occurs more frequently in men while the median age at diagnosis is 68 years. Transitional cell carcinoma (TCC) comprises more than 90% of all bladder cancers with the remainder consisting of squamous cell carcinoma (3%), adenocarcinoma (2%), and small cell carcinoma (less than 1%). TCCs with focal areas of squamous or glandular differentiation are common and are classified and managed as TCC. On the contrary, the biology and management of pure non-TCC bladder cancers differ from those of TCC. Four clinical distinct entities of TCC are recog- nised: superficial papillary tumors (Ta and T1), carcinoma in situ (Tis) muscle-invasive (T2 to T4) and advanced (involved extra-pelvic nodal or distant metastatic) disease. About 75% of patients present with superficial disease that can be gener- ally managed with local therapy, such as transurethral resec- tion and intravescical chemotherapy or immunotherapy. Once muscle invasion has occurred, the prognosis worsens, with 5-year survival of about 60% for patients with carcinoma macroscopically confined to the bladder and only 20-30% for patients with tumors extending beyond the bladder wall (2). The standard treatment for invasive bladder cancer is radical cystectomy with bilateral pelvic lymphadenectomy. Although surgery may be curative, about 50% of patients with muscle- invasive bladder cancer develop metastases within 2 years because of micrometastatic disease probably present at the time of local treatment (3). Herein we discuss the role of systemic chemotherapy, aimed at improving survival for muscle-invasive disease, and palliation for metastatic TCC of the bladder.
    Annals of Oncology 06/2005; 16 Suppl 4(suppl 4):iv85-89. DOI:10.1093/annonc/mdi914 · 7.04 Impact Factor
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    ABSTRACT: Despite remarkable progress in therapeutic options for the management of bladder cancer, it remains a challenge for urologists to achieve successful outcomes in the treatment of both superficial and invasive bladder cancers. In this review, recent advances in the field of antisense oligodeoxynucleotide therapy targeting several genes playing functionally important roles in the progression and recurrence of bladder cancer are summarized. Data showing the synergistic antitumor activities of antisense oligodeoxynucleotide therapy, combined with several treatments, including cytotoxic chemotherapy, radiation and other molecular targeting therapies, are also presented. Finally, the future direction of antisense oligodeoxynucleotide therapy in the therapeutic strategy of bladder cancer is discussed. These findings may help clarify the significance of antisense oligodeoxynucleotide therapy as an attractive alternative to conventional strategies.
    Expert Review of Anti-infective Therapy 01/2006; 5(6):1001-9. DOI:10.1586/14737140.5.6.1001 · 2.25 Impact Factor
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