Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Invest New Drugs. 2011 Dec;29(6):1488-93. doi: 10.1007/s10637-010-9485-4. Epub 2010 Jul 6.
Gemcitabine and cisplatin combination chemotherapy have been shown to have promising efficacy for the treatment of advanced biliary tract cancer (BTC) as a first-line chemotherapy. However, this treatment has not been approved for clinical practice in Japan. Oral fluoropyrimidines (e.g., S-1 and capecitabine) are also promising agents that are widely used with or without gemcitabine. Unfortunately, there is no standard chemotherapy for patients refractory to gemcitabine and oral fluoropyrimidine. We conducted a feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with advanced BTC who are refractory to gemcitabine and S-1. Gemcitabine (1,000 mg/m(2)) and cisplatin (25 mg/m(2)) were administered intravenously on days 1 and 8, and this regimen was repeated every 3 weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty patients with pathologically confirmed BTC were enrolled. Gemcitabine and cisplatin combination chemotherapy was administered as a second-line chemotherapy in thirteen patients and as a third-line chemotherapy in seven patients. Tumor response did not occur in any of the cases. Fourteen patients demonstrated stable diseases, and the disease control rate was 70%. Median overall survival and time-to-progression were 5.9 months (95% CI, 3.9-11.3 months) and 3.6 months (95% CI, 2.2-4.2 months), respectively. Grade 3/4 toxicities included leucopenia (35%), neutropenia (35%), anemia (20%), and thrombocytopenia (15%). Two patients treated for approximately 1 year developed cisplatin-related toxicities. In conclusion, gemcitabine and cisplatin combination chemotherapy produces a limited tumor response in BTC, but may prolong patient's survival.
吉西他滨和顺铂联合化疗作为一线化疗方案,已被证明对晚期胆道癌(BTC)具有良好的疗效。然而,这种治疗方法尚未在日本获得临床批准。口服氟嘧啶类药物(如 S-1 和卡培他滨)也是很有前途的药物,与吉西他滨联合使用或不联合使用均可。不幸的是,对于吉西他滨和口服氟嘧啶类药物耐药的患者,没有标准的化疗方案。我们对吉西他滨和 S-1 耐药的晚期 BTC 患者进行了吉西他滨和顺铂联合化疗的可行性研究。吉西他滨(1000mg/m²)和顺铂(25mg/m²)于第 1 天和第 8 天静脉给药,每 3 周重复一次。每两个周期使用实体瘤反应评价标准 1.0 评估肿瘤反应。共有 20 例经病理证实的 BTC 患者入组。吉西他滨和顺铂联合化疗在 13 例患者中作为二线化疗,在 7 例患者中作为三线化疗。没有发生肿瘤反应。14 例患者表现为稳定疾病,疾病控制率为 70%。中位总生存期和无进展生存期分别为 5.9 个月(95%CI,3.9-11.3 个月)和 3.6 个月(95%CI,2.2-4.2 个月)。3/4 级毒性包括白细胞减少(35%)、中性粒细胞减少(35%)、贫血(20%)和血小板减少(15%)。两名患者接受约 1 年的治疗后出现了顺铂相关的毒性。总之,吉西他滨和顺铂联合化疗方案在 BTC 中产生的肿瘤反应有限,但可能延长患者的生存时间。