New developments in cancer treatment with the novel thymidylate synthase inhibitor raltitrexed ('Tomudex').
New developments in cancer treatment with the novel thymidylate synthase inhibitor raltitrexed ('Tomudex').
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DOI：
10.1038/bjc.1998.423
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发表时间：
1998
影响因子：
8.8
通讯作者：
Blackledge, G
中科院分区：
文献类型：
--
作者：
Blackledge, G
在证实了雷替曲塞（“Tomudex”）的疗效、耐受性和生活质量获益（主要是在晚期结直肠癌和其他癌症中）后，正在对与其他药物联合治疗结直肠癌和其他肿瘤类型患者进行广泛评价。临床前观察到雷替曲塞与其他细胞毒性药物或放疗联合给药时活性增强，以及初步结果显示雷替曲塞在结直肠癌以外的癌症患者中的活性，促使了这项工作。雷替曲塞目前作为单药治疗正在I期和II期癌症研究中进行研究，包括头颈癌、耐药前列腺癌、儿童和成人白血病和实体瘤以及软组织肉瘤。此外，第一阶段临床试验正在评估该药物与实体瘤中的紫杉烷类（紫杉醇）、胃癌中的蒽环类（多柔比星）、晚期结肠直肠癌中的拓扑异构酶I抑制剂（CPT-11）和5-氟尿嘧啶（输注和推注方案）、各种肿瘤中的铂化合物（奥沙利铂和顺铂）以及直肠癌中的放射疗法的组合。初步报告表明，正在研究的组合具有良好的耐受性和可接受性，迄今为止没有报道剂量限制性毒性，以及一些早期疗效迹象。
Following the demonstration of efficacy, tolerability and quality-of-life benefits of raltitrexed ('Tomudex'), principally in advanced colorectal but also in other cancers, an extensive evaluation of combination therapy with other agents in patients with colorectal and other tumour types is being undertaken. This work has been prompted by preclinical observations of enhanced activity of raltitrexed when coadministered with other cytotoxic agents or radiotherapy and by preliminary results showing the activity of raltitrexed in patients with cancers other than colorectal. Raltitrexed is currently being investigated as monotherapy in phase I and II cancer studies, including head and neck cancer, hormone-resistant prostate cancer, paediatric and adult leukaemias and solid tumours, and soft tissue sarcoma. In addition, phase I clinical trials are evaluating the drug in combination with taxanes (paclitaxel) in solid tumours, anthracyclines (doxorubicin) in gastric carcinoma, topoisomerase I inhibitors (CPT-11) and 5-fluorouracil (both infusion and bolus regimens) in advanced colorectal cancer, platinum compounds (oxaliplatin and cisplatin) in a variety of tumours and radiotherapy in rectal cancer. Preliminary reports indicate good tolerability and acceptability of the combinations being investigated, with no dose-limiting toxicity being reported to date, and some early indications of efficacy.