BERKELEY, CA (UroToday.com) - Urothelial cancer is a chemotherapy-sensitive malignancy, with the regimen of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) until recently considered to be the first choice for chemotherapy, however its adverse effects and poor long-term outcome results remain challenging problems. In addition, effective treatment for the cases showing resistance to M-VAC or recurrent cases after first-line chemotherapy has not to been established.
The combination of gemcitabine and cisplatin (GC) is thought to be a promising substitution as compared to M-VAC. In a randomized controlled trial that compared between the combinations of GC and M-VAC, no significant differences in overall response rate, time to progression, and overall survival were found between the two arms, while the rates of incidence of myelosuppression, oral mucosal impairment, body weight loss, and general fatigue were significantly lower with GC as compared to M-VAC. Furthermore, the dose intensity of the GC arm was significantly superior to that of the M-VAC arm.
The controversial issue about chemotherapy for urothelial cancer is that appropriate chemotherapy for cisplatin-resistant or -recurrent cases has not been established. A combination of taxanes with gemcitabine and/or platinum-based agents likely provides clinical benefits following M-VAC or GC therapy. Both the combination chemotherapy using paclitaxel and gemcitabine, and another combination using gemcitabine, docetaxel and carboplatin showed the beneficial effect on the patients having had the resistance against cisplatin-based chemotherapy. Also, a combination chemotherapy including ifosfamide and/or nedaplatin may be applicable for cisplatin-resistant cases. Recurrent cases after first-line chemotherapy frequently show myelo-functional impairment, in addition to worsened performance status and/or impaired renal function, thus second-line chemotherapy should be planned considering the patients’ healthy balance between chemotherapeutic efficacy and maintenance of quality of life.
In recent years, based on the understanding of cancer pathogenesis at the molecular level, some studies have investigated the efficacy of molecular target therapies in patients with progressive advanced urothelial cancer and some of them, such as trastuzumab (a humanized monoclonal antibody that binds to HER-2/neu) and bevacizumab (a recombinant monoclonal antibody for circulating VEGF-A) currently available seem to be effective on advanced urothelial cancer.
In the future, additional investigations using various trial designs may lead to new therapeutic strategies with molecular target agents.
Written by:
Mitsui Y, Yasumoto H, Arichi N, Honda S, Shiina H, and Igawa M. as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
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