title: Raltitrexed (Tomudex) concomitant with radiotherapy as adjuvant treatment for patients with rectal cancer: preliminary results of phase I studies.
abstract: Radiotherapy, either alone or in combination with chemotherapy, may reduce local recurrence of rectal cancer following surgery and improve survival of patients with operable and advanced/recurrent/inoperable disease. Chemotherapy with 5-fluorouracil in combination with radiotherapy has been used both before and after surgery; however, the optimum schedule is unclear. In addition, alternative chemotherapy with raltitrexed (Tomudex) may be more convenient and better tolerated. The preliminary results of three phase I dose-finding studies are described, combining escalating doses of raltitrexed with radiotherapy as pre- or postoperative treatment for operable rectal cancer or as treatment for advanced/inoperable/recurrent rectal cancer. The recommended dose of raltitrexed when combined with adjuvant radiotherapy is likely to be 2.6 mg/m2. This is a small dose reduction compared with the dose of raltitrexed for the treatment of advanced colorectal cancer (3.0 mg/m2); however, toxicity appears to be lower using the pre-operative approach. Neo-adjuvant therapy with raltitrexed plus radiotherapy also demonstrated clinical activity in the pre-operative study, which showed that 22% of patients achieved a complete response and 56% a partial response. Once the recommended dose has been defined in each setting, large-scale studies will be undertaken as appropriate.
authors.affiliation: Department of Clinical Oncology, Christie Hospital, Manchester, U.K.
authors.forename: R
authors.initials: R
authors.lastname: James
authors.forename: P
authors.initials: P
authors.lastname: Price
authors.forename: V
authors.initials: V
authors.lastname: Valentini
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D013876:Thiophenes; C068874:raltitrexed