There is no established treatment for patients with progressive disease of urothelial carcinoma after first-line platinum-based chemotherapy. Recently, treatment with vinflunine plus best supportive care (BSC) was demonstrated to significantly improve overall survival in eligible patients compared to patients who received BSC alone in a phase III trial, and this treatment has been approved in Europe as a second-line therapy for advanced urothelial carcinoma.
Some patients whose disease progresses after a second-line chemotherapy are willing to receive additional cancer-control treatment in addition to BSC. In this study, our aim was to determine whether gemcitabine and nedaplatin (GN) that is reacted with antitumor mechanism is an effective treatment for patients with metastatic UC who have previously been treated with gemcitabine and paclitaxel (GP) followed by methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC).
Between February 2009 and August 2013, 30 patients were treated with GP as a second-line chemotherapy. Patients had measurable or assessable cancerous lesions which were histologically proven to be locally advanced or metastatic UC. All patients had received surgical treatment or biopsy of the primary lesions and chemotherapy consisting of GP followed by MVAC. The GN protocol was similar to the gemcitabine and cisplatin protocol. All patients received gemcitabine 1000 mg/m2 on days 1, 8, and 15 and nedaplatin 70 mg/m2 on day 2, and the treatment cycle was repeated every 4 weeks.
Ten eligible patients received at least two cycles of GN and were evaluated for response. The median doses of gemcitabine and nedaplatin were 750 mg/m2 (range, 490−1000 mg/m2) and 52.5 mg/m2 (range, 35−70 mg/m2), respectively. Dose reduction was required in all patients. The median number of treatment cycles was 3.5. One patient had partial response, and three had stable disease. The disease-control rate was 40%, the median overall survival was 8.8 months, and the median progression-free survival was 5.0 months. The median overall survival times for the first-line and second-line therapies were 29.1 and 13.9 months, respectively. The ten patients were subdivided into two groups: a controlled-disease group consisting of patients who showed partial response or stable disease (n = 4) and an uncontrolled-disease group consisting of patients who showed progressive disease (n = 6). Median overall survival times in the controlled-disease and uncontrolled-disease groups after GN were 14.2 and 6.2 months, respectively, but the difference between the groups was not statistically significant. Myelosuppression was the most common toxicity. There were no therapy-related deaths.
Brain metastasis occurs in less than 1% of patients with UC. In our study, three patients developed brain metastases. Although our study did not provide any clues regarding the treatment of brain metastasis, we may need to pay attention and to detect it early leading to keeping patients’ quality of life after the number of lines of chemotherapy. Despite the lack of a discernible significant impact of the number of prior lines of therapy on clinical outcomes, careful selection of a chemotherapy protocol, starting from the time of the treatment-naïve condition, on the basis of the specific chemotherapeutic agents administered is nevertheless warranted. Gemcitabine and nedaplatin chemotherapy is a favorable third-line chemotherapeutic option for patients with metastatic urothelial carcinoma. Given the safety and benefit profile seen in this study, further prospective trials are warranted to implication of our results with regard to strategic chemotherapy for patients with advanced or metastatic urothelial carcinoma.
Written by:
Kazumasa Matsumoto
Department of Urology, Kitasato University School of Medicine, Japan.