Phase I/II Study to Investigate the Use of Gemcitabine in Combination with Raltitrexed in Locally Advanced or Metastatic Pancreatic Adenocarcinoma

Abstract

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.