Overview of the tolerability of 'Tomudex' (raltitrexed): collective clinical experience in advanced colorectal cancer.
The tolerability of raltitrexed ('Tomudex', formerly ZD1694) was examined during phase I, II and III clinical studies involving around 1000 patients with advanced colorectal cancer. The dose-limiting toxicities in the phase I studies were gastrointestinal toxicity, haematological suppression and asthenia. Adverse events during phase II and III studies were consistent with those seen during phase I. In all comparative studies, mucositis and leucopenia were markedly less frequent and less severe in patients treated with raltitrexed than with 5-fluorouracil + leucovorin.Thrombocytopenia was more common with raltitrexed but was not associated with an increase in clinically significant haemorrhage. Elevated transaminases were frequently reported with raltitrexed but were usually reversible with continued dosing and were not associated with clinical sequelae. Patients treated with 5-fluorouracil + leucovorin experienced greater toxicity during early treatment cycles than those treated with raltitrexed. Fewer dosage reductions due to toxicity and greater quality-of-life benefits were observed in these early treatment cycles in patients treated with raltitrexed. Moreover, the incidence of fatal adverse events in patients given the recommended dose of raltitrexed was similar between groups. Raltitrexed thus provides some tolerability advantages compared with 5-fluorouracil + leucovorin, mainly with respect to leucopenia and mucositis, and less overall toxicity in early treatment cycles. The toxicity profile of raltitrexed is that expected of an antimetabolite.
Zalcberg
J
J
Division of Haematology and Medical Oncology, Peter McCallum Cancer Institute, Victoria, Australia.
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D013876:Thiophenes; C068874:raltitrexed