III Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Ruprecht-Karls-Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
J Cancer Res Clin Oncol. 2010 Dec;136(12):1845-51. doi: 10.1007/s00432-010-0843-6. Epub 2010 Mar 12.
Preclinical data indicate the improvement of the antitumor activity of capecitabine by mitomycin C and docetaxel through upregulation of thymidine phosphorylase activity. Therefore, we have established a combination regimen of these drugs (DocMitoCape), which demonstrated preliminary activity especially in bile duct and pancreatic carcinoma.
Here we report the safety and efficacy of the DocMitoCape regimen in pre-treated patients with gallbladder, bile duct, or pancreatic carcinoma. Treatment consisted of capecitabine (2,000 mg/m(2) days 1-14) in combination with docetaxel (40 mg/m(2) day 1) and mitomycin C (4 mg/m(2) day 1). Cycles were repeated on day 22. Toxicity was graded according to NCI-CTC criteria, and the antitumor activity was assessed by RECIST criteria.
Twenty-eight pre-treated patients with a median age of 59 suffering from pancreatic, gallbladder, intra- (IHCCC) or extrahepatic (EHCCC) bile duct carcinoma were included. Eleven patients had received ≥2 lines of prior chemotherapy. A total of 183 and a median of six cycles were administered (range 1-21). The mean dose intensity was as follows (cycles 1-2/3-4; %): capecitabine 97/92, docetaxel 100/100, mitomycin C 99/100. Main adverse events grades 2/3/4 were (n): leukocytopenia 3/2/2, anemia 13/4/0, thrombocytopenia 3/1/0, nausea/vomiting 2/1/0, diarrhea 5/1/0, hand-foot-skin reaction 7/0/0. Six patients achieved partial and seven patients minor remissions, while six patients had stable disease adding to a tumor control rate of 68%. Median progression-free and overall survival was 4.5 (range 1.0-44.9) and 6.8 months (range 1.5-44.9), respectively, calculated from the start of treatment.
In all, the DocMitoCape regimen exhibited a favorable safety profile and a high rate of tumor stabilizations in patients with pre-treated gallbladder, bile duct and pancreatic carcinoma. It might be considered after failure of standard regimens in these types of cancer.
临床前数据表明，通过上调胸苷磷酸化酶活性，卡培他滨与丝裂霉素 C 和多西紫杉醇联合可提高抗肿瘤活性。因此，我们建立了这些药物的联合方案（DocMitoCape），该方案在胆管癌和胰腺癌中显示出初步疗效。
在此，我们报告了在先前治疗过的胆囊癌、胆管癌或胰腺癌患者中，DocMitoCape 方案的安全性和疗效。治疗方案包括卡培他滨（2000mg/m2，第 1-14 天）联合多西紫杉醇（40mg/m2，第 1 天）和丝裂霉素 C（4mg/m2，第 1 天）。第 22 天重复周期。毒性按 NCI-CTC 标准分级，根据 RECIST 标准评估抗肿瘤活性。
共纳入 28 例先前治疗过的中位年龄为 59 岁的胰腺癌、胆囊癌、肝内（IHCCC）或肝外（EHCCC）胆管癌患者。11 例患者接受了≥2 线化疗。共接受了 183 个周期，中位数为 6 个（范围 1-21）。平均剂量强度如下（周期 1-2/3-4；%）：卡培他滨 97/92，多西紫杉醇 100/100，丝裂霉素 C 99/100。2/3/4 级主要不良事件（n）：白细胞减少症 3/2/2、贫血症 13/4/0、血小板减少症 3/1/0、恶心/呕吐 2/1/0、腹泻 5/1/0、手足皮肤反应 7/0/0。6 例患者获得部分缓解，7 例患者获得轻微缓解，6 例患者病情稳定，肿瘤控制率为 68%。从治疗开始计算，中位无进展生存期和总生存期分别为 4.5 个月（范围 1.0-44.9）和 6.8 个月（范围 1.5-44.9）。
总体而言，DocMitoCape 方案在先前治疗过的胆囊癌、胆管癌和胰腺癌患者中显示出良好的安全性和较高的肿瘤稳定率。在这些类型的癌症中，标准治疗方案失败后可以考虑使用该方案。
