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patient cancer rectal cancer model docetaxel group study rectal clearance brostallicin pharmacokinetic liver grade lf abnormalities treatment abnormality function parameter docetaxel clearance toxicity surgery cycle value ermbt variability neutropenia 12.5 mg /m excision plasma concentration covariate population level transanal endoscopic microsurgery analysis netherland number response table cyp 3a activity activity phase department preoperative oncol committee member erythromycin breath test result effect chemoradiation trial tumor 12.5 course neoadjuvant tumour rectum 15 mg /m grade 4 neutropenia binding model radboud university nijmegen 10 mg /m dose level liter transanal liver function grade 3 antitumor activity therapy 3 weeks centre recurrence group 3 b liver impairment phosphatase tme surgery oncology figure radiotherapy