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dc.contributor.authorBotwood, Nicholasen
dc.contributor.authorJames, Roger Den
dc.contributor.authorVernon, Cen
dc.contributor.authorPrice, Patricia Men
dc.date.accessioned2009-11-18T11:30:10Z
dc.date.available2009-11-18T11:30:10Z
dc.date.issued2000-08
dc.identifier.citationRaltitrexed ('Tomudex') and radiotherapy can be combined as postoperative treatment for rectal cancer. 2000, 11 (8):1023-8 Ann. Oncol.en
dc.identifier.issn0923-7534
dc.identifier.pmid11038040
dc.identifier.urihttp://hdl.handle.net/10541/86366
dc.description.abstractBACKGROUND: The optimal adjuvant therapy for operable rectal cancer is likely to be a combination of radiotherapy and chemotherapy. Raltitrexed ('Tomudex') is a specific thymidylate synthase inhibitor with a convenient administration schedule, acceptable and manageable toxicity, radiosensitising properties, and proven efficacy in the treatment of advanced colorectal cancer. It may, therefore, offer advantages compared with standard 5-FU chemotherapy regimens used in colorectal cancer. The aim of this phase I, dose-escalation study was to determine the recommended dose of raltitrexed for use with postoperative pelvic radiotherapy in patients with rectal cancer. PATIENTS AND METHODS: Patients with resected Dukes' stage B or C rectal cancer were treated with a combination of raltitrexed and radiotherapy (50.4 Gy at 1.8 Gy per fraction over five to six weeks). At least three patients were treated at each of three escalating raltitrexed dose levels (2.0, 2.6 and 3.0 mg/m2) once every three weeks. Toxicity was assessed by the recording of WHO adverse events and biochemistry and haematology determinations. RESULTS: A total of 22 patients entered the study, 17 of whom had Dukes' stage C disease. All three patients entered at a dose level of 3.0 mg/m2 experienced dose-limiting toxicity (DLT) (2 patients had grade 3 leucopenia and 1 patient had grade 2 leucopenia and grade 3 diarrhoea); however, only 2 of 1 patients entered at a dose level of 2.6 mg/m2 experienced DLT (1 patient had grade 4 neutropenia and 1 patient died probably due to aspiration pneumonia unrelated to treatment). The most common haematological toxic events were leucopenia (8 patients) and anaemia (6 patients). Only four haematological or biochemical toxic events were of grade 3 or 4. Other common toxicities were diarrhoea and nausea, which occurred in 15 and 9 patients, respectively. CONCLUSIONS: This study demonstrates that raltitrexed can be combined with postoperative radiotherapy for treatment of patients with Dukes' stage B or C rectal cancer. The recommended dose of raltitrexed in this setting is 2.6 mg/m2, which is close to the full monotherapy dose.
dc.language.isoenen
dc.subjectRectal Canceren
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAntimetabolites, Antineoplastic
dc.subject.meshChemotherapy, Adjuvant
dc.subject.meshCombined Modality Therapy
dc.subject.meshDose-Response Relationship, Drug
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshNeutropenia
dc.subject.meshPneumonia
dc.subject.meshQuinazolines
dc.subject.meshRadiotherapy, Adjuvant
dc.subject.meshRectal Neoplasms
dc.subject.meshThiophenes
dc.subject.meshTreatment Outcome
dc.titleRaltitrexed ('Tomudex') and radiotherapy can be combined as postoperative treatment for rectal cancer.en
dc.typeArticleen
dc.contributor.departmentDepartment of Clinical Oncology, Hammersmith Hospital, Imperial College School of Medicine, London, UK.en
dc.identifier.journalAnnals of Oncologyen
html.description.abstractBACKGROUND: The optimal adjuvant therapy for operable rectal cancer is likely to be a combination of radiotherapy and chemotherapy. Raltitrexed ('Tomudex') is a specific thymidylate synthase inhibitor with a convenient administration schedule, acceptable and manageable toxicity, radiosensitising properties, and proven efficacy in the treatment of advanced colorectal cancer. It may, therefore, offer advantages compared with standard 5-FU chemotherapy regimens used in colorectal cancer. The aim of this phase I, dose-escalation study was to determine the recommended dose of raltitrexed for use with postoperative pelvic radiotherapy in patients with rectal cancer. PATIENTS AND METHODS: Patients with resected Dukes' stage B or C rectal cancer were treated with a combination of raltitrexed and radiotherapy (50.4 Gy at 1.8 Gy per fraction over five to six weeks). At least three patients were treated at each of three escalating raltitrexed dose levels (2.0, 2.6 and 3.0 mg/m2) once every three weeks. Toxicity was assessed by the recording of WHO adverse events and biochemistry and haematology determinations. RESULTS: A total of 22 patients entered the study, 17 of whom had Dukes' stage C disease. All three patients entered at a dose level of 3.0 mg/m2 experienced dose-limiting toxicity (DLT) (2 patients had grade 3 leucopenia and 1 patient had grade 2 leucopenia and grade 3 diarrhoea); however, only 2 of 1 patients entered at a dose level of 2.6 mg/m2 experienced DLT (1 patient had grade 4 neutropenia and 1 patient died probably due to aspiration pneumonia unrelated to treatment). The most common haematological toxic events were leucopenia (8 patients) and anaemia (6 patients). Only four haematological or biochemical toxic events were of grade 3 or 4. Other common toxicities were diarrhoea and nausea, which occurred in 15 and 9 patients, respectively. CONCLUSIONS: This study demonstrates that raltitrexed can be combined with postoperative radiotherapy for treatment of patients with Dukes' stage B or C rectal cancer. The recommended dose of raltitrexed in this setting is 2.6 mg/m2, which is close to the full monotherapy dose.


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