Ann Oncol. 2001 Apr;12(4):569-71. doi: 10.1023/a:1011178111295.
A 59-year-old Caucasian male was diagnosed with a moderately differentiated adenocarcinoma of the ascending colon and underwent a right hemicolectomy and lymphadenectomy in October 1999. The tumor was classified as pT3pN2M0, grade 3 and grouped as UICC stage III. Standard adjuvant treatment with 5-FU and folinic acid was initiated within two weeks after surgery 5-FU (425 mg/m2 ) and folinic acid (20 mg/m2 ) were given as an l v bolus on days 1-5. The in-patient treatment was initially tolerated well and he was discharged after the last application of the first treatment cycle on October 29, 1999 On November 3 he presented with severe stomatitis and dysphagia and had to be re-admitted to the hospital During the first two weeks of this longterm hospitahzation, the patient's condition worsened progressively The stomatitis did not improve despite local therapy. He developed severe bone marrow depression with peripheral pancytopenia. Due to febrile leukopenia with temperatures up to 39 3°C on November 6, treatment with antibiotics and granulocyte-colony stimulating factor was initiated. The further course was complicated due to pneumonia, repeated aspiration and respiratory insufficiency requiring mechanical ventilation Furthermore he developed left cardiac insufficiency of unknown etiology After gradual improvement, the patient left the intensive care unit and was discharged in good condition on December 21. No further adjuvant chemotherapy was administered, and the patient was followed closely. The severe toxicity observed during the first cycle of standard 5-FU-treatment rose suspicion of a defect in drug metabolism As we expected a hereditary genetic defect, punne and pynmidine metabolites and DPDactivity were determined in urine and plasma of the patient and his healthy son according to methods previously described [9] (Table 1). Uracil and uric acid were mildly elevated in plasma samples of the patient, whereas thymine, 5-OH-methyluracil, hypoxanthine and xanthine were within the normal range (data not shown). DPD activity was present in mononuclear cells of the patient, but was decreased compared to that of healthy controls (n = 21) and was comparable to the DPD activity observed in obligate heterozygote individuals (n = 13). The son had decreased DPD activity in mononuclear cells as well, which was comparable to obligate heterozygotes. Based on these findings, both father and son were diagnosed of having a hereditary form of partial DPD deficiency. In February 2000 the patient was complaining of fatigue and abdominal pain. A CT scan revealed metachronous inoperable liver metastases, confirmed by a significant rise in serum CEA In order to avoid the further administration of fluoropynmidines, we suggested palliative treatment with single agent lnnotecan, which was then safely administered over three consecutive cycles at a dose of 125
