4Gy (Hofheinz et al, 2005)). selleckchem Secondary end points comprise the assessment of the rate of local and distant failure. The statistical calculation was made on toxicity issues and was based on the definition of dose-limiting toxicity (DLT) used in our previous phase-I trial (Hofheinz et al, 2005). Dose-limiting toxicity had been defined in this phase-I trial by the occurrence of one of the following adverse events: grade 4 leukocytopenia/neutropenia or thrombocytopenia, symptomatic thrombocytopenia, grade 3/4 febrile neutropenia, or any grade 3 non-haematological adverse events except renal adverse events (grade 2) and nausea/vomiting. The rate of DLTs during the present phase-II trial should be lower than 17% (ie about one out of six patients).

With a total of 32 patients, a rate of at least 83% of the patients experiencing no DLTs during radiochemotherapy can be assumed using Simon’s two-stage design with a power of 80% and an ��-value of 0.2 if less than five out of 15 (first stage) or eight out of 32 patients (second stage) experienced DLTs. Deadline for the follow-up data evaluation was 31 May 2006. Survival according to Kaplan�CMeier was performed using the Graph-Pad Prism software 4.0 (GraphPad Software, San Diego, CA, USA). Survival was calculated from the start of study treatment until patients death or the date of last follow-up. Progression free-survival was calculated from the start of treatment until the detection of local recurrence or distant metastases. RESULTS Out of 36 patients entering this single-center trial, 33 had newly diagnosed rectal adenocarcinoma, and three patients had a local recurrence at the anastomotic site (Table 1).

None of these patients had received prior pelvic radiotherapy. The median distance from the lower border of the primary to the anal verge was 5cm (2�C15cm). Most tumours were located in the lower third of the rectum (n=21 patients). Only five patients had tumours in the upper third. Table 1 Patient and tumour characteristics Two patients with potentially resectable hepatic metastases and one patient with suspected pleural carcinomatosis (not histologically verified) were included in this trial. Toxicity and dose intensity Acute toxicity during chemoradiotherapy is listed in Table 2. The most frequently observed haematologic adverse event was leucocytopenia. Nine out of 36 patients had grade 3 or 4 leukocytopenia (25%), but no episode of neutropenic fever was reported. No patient received prophylactic or therapeutic granulocyte colony-stimulating factors during the study. Mild thrombocytopenia was only seen in two patients. The median decrease of haemoglobin GSK-3 level was 2.1gdl?1 (ranging from 0.0 to 3.