Author(s): Okuyama Y, Hazama S, Nozawa H, Kobayashi M, Takahashi K,
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Abstract OBJECTIVES: This is the first phase II study to evaluate the efficacy and tolerability of the first-line FOLFIRI, as well as the influence of uridine diphosphate glucuronosyl transferase 1, family polypeptide A1 gene (UGT1A1) 28/6 polymorphism, in Japanese metastatic colorectal cancer patients. METHODS: Fifty-two patients were enrolled in this study and were administrated FOLFIRI (irinotecan; 150 mg/m(2)) as first-line chemotherapy. Thirty-nine patients accepted the evaluation of UGT1A1 genotypes. In patients with UGT1A1 28 homozygosity, the starting dose was reduced (100 mg/m(2)) according to the Food and Drug Administration recommendation and our previous phase I study. RESULTS: After a median follow-up period of 22 months, complete response was achieved in 1.9\%, partial response in 38.5 \%, stable disease in 51.9\% and progressive disease in 3.9\%. The overall response rate was 40.4\%, the disease control rate was 92.3\% and the median overall survival time was 22.3 months. The major toxicity was grade 3-4 neutropenia in 44.2\%. There was no definite relation between UGT1A1 28, 6 polymorphisms and toxicity. However, homozygosity for UGT1A1 28 or UGT1A1 6 and double heterozygosity for both UGT1A1 28 and UGT1A1 6 were significantly associated with severe neutropenia in metastatic colorectal cancer patients (P< 0.001). CONCLUSIONS: FOLFIRI is effective and tolerable for Japanese metastatic colorectal cancer patients. Homozygosity for UGT1A1 28 or 6 and heterozygosity for both UGT1A1 28 and 6 are associated with severe neutropenia.
This article was published in Jpn J Clin Oncol
and referenced in Journal of Pharmacogenomics & Pharmacoproteomics