AIMS AND BACKGROUND: The availability of new drugs offers the opportunity to improve the outcome of locally advanced @entity5 . Raltitrexed and @entity901 are effective in advanced @entity14 with acceptable @entity137 and can act as radiation enhancers as shown in phase I-II studies. The aim of the study was thus to determine the recommended dose of @entity901 concomitantly administered with raltitrexed and concurrent preoperative radiotherapy in @entity1 with stage II-III extraperitoneal @entity5 . METHODS: From September 2001 to September 2002, 18 consecutive @entity1 with T3/T4 @entity5 were treated at our Institution with preoperative chemoradiation followed by surgery after 6-8 weeks. Pelvic radiotherapy was delivered at a dose of 45 Gy in 25 fractions in 5 weeks followed by a 5.4 Gy boost at 1.8 Gy daily. Concomitant chemotherapy consisted of 3 mg/m2/i.v. of raltitrexed on days 1, 19, 38 of radiotherapy treatment with incremental doses of @entity901 according to dose finding rules (4 dose levels: 65, 85, 110, 130 mg/m2). Dose-limiting @entity137 for @entity901 was defined as either grade 3-4 hematological or grade 3-4 gastrointestinal or neurological @entity137 . We studied a minimum of 3 @entity1 at each dose level. RESULTS: Three @entity1 were treated at 65, 85, and 110 mg/m2/i.v., respectively, while 9 @entity1 were recruited at the last dose level. Neither grade 3-4 gastrointestinal nor neurological @entity137 were documented. Dose-limiting @entity137 was documented in 2/9 subjects at the 130 mg/m2 level consisting of grade 3 transient asymptomatic @entity1431 . Thirteen @entity1 developed transient increase of one or more liver enzymes (grade 3-4) and 2 @entity1 developed grade 3 perineal @entity1909 . All @entity1 received the programmed dose of radiotherapy. The chemotherapy regimen was not completed in 4 cases due to grade 2 protracted @entity1431 . CONCLUSIONS: The maximum tolerated dose of @entity901 was not reached at the maximum dose level (i.v.); 130 mg/m2 can therefore be defined as the recommended dose. The combination of @entity901 with raltitrexed and radiotherapy can be considered feasible and well tolerated.

XXXX with raltitrexed and preoperative radiotherapy in @entity5 . A dose finding study.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity901 :: ('MESH:C030110', 'Chemical') :: ['oxaliplatin'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity5 :: ('MESH:D009369', 'Disease') :: ['rectal cancer'] @entity1431 :: ('MESH:D007970', 'Disease') :: ['leukopenia'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer'] @entity1909 :: ('MESH:D003872', 'Disease') :: ['dermatitis']
@entity901 :: (MESH:C030110,Chemical) :: ['Oxaliplatin']
