Bleiberg H
Gastrointestinal Department, Centre des Tumeurs de l'Université, Libre de Bruxelles, Institute Jules Bordet, Belgium.
Eur J Cancer. 1999 Mar;35(3):371-9. doi: 10.1016/s0959-8049(98)00423-7.
Colorectal, gastric and pancreatic cancers are major health problems worldwide. Although surgery is a curative option in 50% of patients with colorectal cancer, it is much less effective in gastric cancer (< 20% of patients) and virtually ineffective in pancreatic cancer. These three cancer types also respond poorly to chemotherapy. CPT-11 (irinotecan), a novel cytotoxic drug, is now available in many countries as a single agent for second-line therapy in metastatic colorectal cancer. The response rate in the pivotal European study of metastatic colorectal cancer patients was 14%, with a median duration of response of 8.5 months. There was also a high rate of disease stabilisation (44%), with a median duration of 4.8 months. Median survival time was 10.4 months. The dose-limiting toxicities (DLT) for CPT-11 are delayed diarrhoea and neutropenia, both of which are schedule dependent and non-cumulative. These encouraging data in second-line therapy support the further study of CPT-11 as first-line therapy for colorectal cancer in combination with other agents. Four Japanese trials of CPT-11 as first- and/or second-line single-agent therapy for advanced gastric cancer report response rates of 18-43%. The median durations for response and survival time in the late phase II trial were 2.3 months and 5.8 months, respectively. These results are in the range of those reported for sequential high-dose methotrexate and 5-fluorouracil (5-FU)/doxorubicin (FAMTX), etoposide/leucovorin/5-FU (ELF) or cisplatin/5-FU therapy in gastric cancer. Data are currently available from five phase II studies of CPT-11 in advanced pancreatic cancer: four Japanese and one European. The response rates ranged from 9 to 19%. The median duration of survival for all treated patients in the European study was 5.2 months. CPT-11 in combination with 5-FU is currently being investigated in Japan, the U.S.A. and Europe in patients with gastrointestinal tumours. CPT-11 is also being evaluated in combination with each of the following agents: oxaliplatin, docetaxel, raltitrexed, etoposide and mitomycin C. Japanese studies of CPT-11 plus cisplatin in patients with gastric cancer have produced response rates of 48-59%. These encouraging data highlight the potential for CPT-11 in combination therapy for gastrointestinal tumours.
结直肠癌、胃癌和胰腺癌是全球主要的健康问题。尽管手术是50%的结直肠癌患者的治愈选择，但对胃癌患者的疗效要低得多（<20%的患者），而对胰腺癌几乎无效。这三种癌症类型对化疗的反应也很差。CPT-11（伊立替康）是一种新型细胞毒性药物，目前在许多国家作为转移性结直肠癌二线治疗的单一药物使用。在欧洲进行的转移性结直肠癌患者的关键研究中，缓解率为14%，中位缓解持续时间为8.5个月。疾病稳定率也很高（44%），中位持续时间为4.8个月。中位生存时间为10.4个月。CPT-11的剂量限制性毒性（DLT）是延迟性腹泻和中性粒细胞减少，这两者都与给药方案有关且无累积性。这些二线治疗中的令人鼓舞的数据支持进一步研究CPT-11作为结直肠癌一线治疗与其他药物联合使用。四项日本关于CPT-11作为晚期胃癌一线和/或二线单一药物治疗的试验报告的缓解率为18% - 43%。在II期后期试验中，缓解和生存时间的中位持续时间分别为2.3个月和5.8个月。这些结果与胃癌中序贯高剂量甲氨蝶呤和5-氟尿嘧啶（5-FU）/阿霉素（FAMTX）、依托泊苷/亚叶酸钙/5-FU（ELF）或顺铂/5-FU治疗所报告的结果范围相同。目前有五项关于CPT-11用于晚期胰腺癌的II期研究数据：四项日本研究和一项欧洲研究。缓解率在9%至19%之间。欧洲研究中所有接受治疗患者的中位生存持续时间为5.2个月。目前日本、美国和欧洲正在对CPT-11联合5-FU治疗胃肠道肿瘤患者进行研究。CPT-11也正在与以下每种药物联合进行评估：奥沙利铂、多西他赛、雷替曲塞、依托泊苷和丝裂霉素C。日本关于CPT-11加顺铂治疗胃癌患者的研究产生的缓解率为48% - 59%。这些令人鼓舞的数据突出了CPT-11在胃肠道肿瘤联合治疗中的潜力。
