Yale Cancer Center, New Haven, CT.
Department of Medicine, Rutgers Cancer Institute of New Jersey, NJ.
Clin Genitourin Cancer. 2018 Dec;16(6):437-444.e6. doi: 10.1016/j.clgc.2018.07.021. Epub 2018 Jul 29.
Sorafenib, an oral tyrosine kinase inhibitor, may enhance the antitumor activity of platinum-based chemotherapy in transitional-cell carcinoma. This study investigated the safety and clinical outcome of adding sorafenib to gemcitabine and carboplatin for patients with advanced transitional-cell carcinoma.
Subjects with metastatic or unresectable chemotherapy-naive TCC with Eastern Cooperative Oncology Group performance status 0 or 1 received gemcitabine (1000 mg/m on days 1 and 8) and carboplatin (area under the curve of 5 on day 1) with sorafenib (400 mg 2 times a day on days 2-19 every 21 days) for 6 cycles. Subjects with stable disease or partial or complete response continued to receive sorafenib until disease progression. The primary end point was progression-free survival (PFS) at 5 months with a secondary end point of response (partial or complete).
Seventeen subjects were enrolled. The median number of cycles of gemcitabine and carboplatin with sorafenib provided was 4.4. A total of 15, 5, and 8 subjects required reductions of gemcitabine, carboplatin, and sorafenib, respectively. Thirteen subjects (76%) required multiple dose reductions. Eleven subjects (65%) were free of progression at 5 months. The overall response rate was 54% (95% confidence interval [CI], 0.28-077), with 4 patients experiencing complete response (24%; 95% CI, 0.07-0.50) and 5 partial response (29%; 95% CI, 0.10-0.56); 7 subjects (41%) had stable disease. Median PFS was 9.5 months (95% CI, 0.43-1.26), and median overall survival was 25.2 months (95% CI, 0.96-5.65). One-year PFS was 31%, and 1-year overall survival was 72%. Eleven subjects (65%) discontinued treatment because of toxicity. There were no toxic deaths.
Gemcitabine and carboplatin with sorafenib showed clinical activity in advanced TCC, with some prolonged progression-free intervals. However, gemcitabine and carboplatin with sorafenib was associated with significant toxicity, causing discontinuation of therapy in most patients.
索拉非尼是一种口服酪氨酸激酶抑制剂，可能会增强铂类化疗药物在移行细胞癌中的抗肿瘤活性。本研究旨在探讨索拉非尼联合吉西他滨和顺铂治疗初治转移性或不可切除的晚期移行细胞癌患者的安全性和临床疗效。
本研究纳入了体力状况（ECOG）评分为 0 或 1 分的转移性或不可切除的初治化疗敏感的移行细胞癌患者，给予吉西他滨（1000mg/m2，第 1 和 8 天）和顺铂（第 1 天 AUC=5）联合索拉非尼（400mg，2 次/天，第 2-19 天，每 21 天为一个周期）治疗 6 个周期。对病情稳定或部分缓解或完全缓解的患者继续给予索拉非尼治疗，直至疾病进展。主要研究终点为 5 个月时的无进展生存期（PFS），次要研究终点为缓解率（部分缓解或完全缓解）。
共纳入 17 例患者，中位接受吉西他滨和顺铂联合索拉非尼治疗的周期数为 4.4 个。分别有 15、5 和 8 例患者需要减少吉西他滨、卡铂和索拉非尼的剂量。13 例（76%）患者需要多次减少剂量。11 例（65%）患者在 5 个月时无疾病进展。总缓解率为 54%（95%CI，0.28-0.77），其中 4 例患者获得完全缓解（24%；95%CI，0.07-0.50），5 例患者获得部分缓解（29%；95%CI，0.10-0.56），7 例患者病情稳定（41%）。中位 PFS 为 9.5 个月（95%CI，0.43-1.26），中位总生存期为 25.2 个月（95%CI，0.96-5.65）。1 年 PFS 率为 31%，1 年总生存率为 72%。11 例（65%）患者因毒性而停止治疗。无治疗相关性死亡。
吉西他滨和顺铂联合索拉非尼治疗晚期移行细胞癌具有一定的临床疗效，可延长无进展生存期。但吉西他滨和顺铂联合索拉非尼治疗相关毒性较大，导致大多数患者停止治疗。
