Raltitrexed ('
Tomudex') monotherapy is a conveniently administered alternative to
5-fluorouracil (5-FU) in the first-line treatment of advanced
colorectal cancer (CRC), and has single-agent activity in a variety of advanced solid tumours. Although both
raltitrexed and
5-FU are
thymidylate synthase inhibitors,
raltitrexed has a specific mode of action and a toxicity profile distinct from
5-FU. The mechanism of action of
raltitrexed is also completely different from that of
oxaliplatin,
irinotecan and other drugs with which it has been combined. These properties, together with preclinical data, suggested that combinations of
raltitrexed with
5-FU, other chemotherapeutic agents, or
radiotherapy could result in improved
therapies for a variety of advanced solid tumours, including advanced CRC. This review outlines the appropriate management of patients treated with
raltitrexed, whether as monotherapy or in combination, and discusses the preliminary results of combination studies with
raltitrexed in a range of tumour types including advanced CRC,
malignant mesothelioma, gastric, pancreatic, head and neck, and non-small-cell
lung cancers. Of particular interest is the combination of
raltitrexed and
oxaliplatin, which has shown promising antitumour effects in first-line treatment of advanced CRC and
malignant mesothelioma, a disease that is refractory to
chemotherapy.