吉西他滨联合雷替曲塞治疗局部晚期或转移性胰腺腺癌的I/II期研究

Michael Agnieszka, M. Hill, A. Maraveyas, H. Wasan, F. Lofts
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引用次数: 1

摘要

胰腺腺癌仍然是最难治疗的癌症之一。雷替曲塞是一种新型喹唑啉类似物,与吉西他滨联合可能会增强抗癌作用,因为这两种药物都通过不同的代谢途径抑制DNA合成。我们报告了一项I/II期研究,增加吉西他滨与雷替曲塞在晚期胰腺腺癌患者中的剂量。该研究在三种不同剂量水平下进行,雷曲塞为3mg/m2,吉西他滨逐渐增加。共招募了24名患者。队列2患者出现意想不到的毒性,58%的患者出现血液学毒性,29%的患者出现恶心和呕吐。多数患者表现为嗜睡,5例达到剂量限制性毒性。24例患者中有2例(8%)出现部分缓解,25%的患者病情稳定,50%的患者病情进展。我们发现雷替曲塞和吉西他滨联合治疗胰腺癌有效,但耐受性差。
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Phase I/II Study to Investigate the Use of Gemcitabine in Combination with Raltitrexed in Locally Advanced or Metastatic Pancreatic Adenocarcinoma
Adenocarcinoma of the pancreas remains one of the most difficult cancers to treat. Raltitrexed, a novel quinazoline analogue, combined with gemcitabine is likely to potentate the anti-cancer effect, as both of those drugs inhibit DNA synthesis via separate metabolic pathway. We report a phase I/II study of increasing dose of gemcitabine with raltitrexed in patients with advanced adenocarcinoma of the pancreas. The study was conducted at three different dose levels with raltitrexed at 3mg/m2 and increasing gemcitabine levels. 24 patients were recruited. Cohort 2 patient developed unexpected toxicity with 58% of patients experiencing haematological toxicity and 29% nausea and vomiting. The majority of patients complained of lethargy and 5 patients reached dose-limiting toxicity. Partial responses were documented in two out of 24 patients (8%), 25% had stable disease and 50% developed progressive disease. We found the combination of raltitrexed and gemcitabine active but poorly tolerated in pancreatic cancer.
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