NEW DEVELOPMENTS IN CANCER-TREATMENT WITH THE NOVEL THYMIDYLATE SYNTHASE INHIBITOR RALTITREXED (TOMUDEX)

Following the demonstration of efficacy, tolerability and quality-of-l ife benefits of raltitrexed ('Tomudex'), principally in advanced color ectal but also in other cancers, an extensive evaluation of combinatio n therapy with other agents in patients with colorectal and other tumo ur types is being undertaken. This work has been prompted by preclinic al observations of enhanced activity of raltitrexed when coadministere d with other cytotoxic agents or radiotherapy and by preliminary resul ts showing the activity of raltitrexed in patients with cancers other than colorectal. Raltitrexed is currently being investigated as monoth erapy in phase I and II cancer studies, including head and neck cancer , hormone-resistant prostate cancer, paediatric and adult leukaemias a nd solid tumours, and soft tissue sarcoma. In addition, phase I clinic al trials are evaluating the drug in combination with taxanes (paclita xel) in solid tumours, anthracyclines (doxorubicin) in gastric carcino ma, topoisomerase I inhibitors (CPT-11) and 5-fluorouracil (both infus ion and bolus regimens) in advanced colorectal cancer, platinum compou nds (oxaliplatin and cisplatin) in a variety of tumours and radiothera py in rectal cancer. Preliminary reports indicate good tolerability an d acceptability of the combinations being investigated, with no dose-l imiting toxicity being reported to date, and some early indications of efficacy.