Safety and efficacy of combination therapy with low-dose gemcitabine, paclitaxel, and sorafenib in patients with cisplatin-resistant urothelial cancer.

Abstract

418 Background: Various chemotherapeutic regimens have been examined. However, there is no effective regimen, and some studies have been stopped because of severe adverse events. Therefore, maintenance of quality of life is also important. This study examine the anti-cancer effects, changes in the quality of life (QoL), and safety of combined therapy of low dose gemcitabine, paclitaxel, and sorafenib in these patients. Methods: Twenty patients were treated with gemcitabine (700 mg/m2 on day 1), paclitaxel (70 mg/m2 on day 1), and sorafenib (400 mg/day on days 8–22). QoL and pain relief were evaluated using the short-form survey (SF)-36 and the visual analogue scale (VAS). Data on QoL and pain were collected on the day before the first cycle was started and 8 weeks after starting the therapy. A total of 124 cycles were administered and the median (IQR) number of treatment cycles per patient was 5 (3–8) cycles. Results: Among 20 patients, 12 and 8 patients were received as 2nd- and 3rd-line therapy, respectively. In 2nd-line therapy, median / interquartile range of VAS scores after therapy (2 / 2–3) significantly decreased (p = 0.012) compared to their pretreatment levels (3 / 2–5). Likewise, a significant decrease was also found in 3rd-line therapy (5/ 4–6 to 3/ 2–3, p = 0.028). Similar findings were confirmed by the bodily pain score from the SF-36 survey. A decrease in analgesic consumption was seen in three patients (17.6%), and 2 patients (11.8%) was improved the pain without increasing the dose. Complete responses, partial responses, and stable disease were found in 0 (0.0%), 1 (5.0%), and 13 patients (65%), respectively. The period of overall survival after starting of this therapy was 7 (5–11) months. Three patients (15.0%) stopped therapy because of grade 3 fatigue and hand-foot reactions. Conclusions: Combined therapy of low dose gemcitabine, paclitaxel, and sorafenib was well tolerated. QoL was maintained and improvements in their pain levels were found after treatment. We suggest that this treatment regimen is worthy of consideration as 2nd- and 3rd-line therapy for patients with CDDP-resistant UC. Clinical trial information: 000010957.