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
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
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