[Single nucleotide polymorphism analysis in the GSTP1 and ABCC2 genes about neuropathy by the Oxaliplatin].
The appearance of neuropathy that is a harmful phenomenon of Oxaliplatin, the key drug of FOLFOX, is strongly concerned in individual pharmacological variability. Further more, the frequency of neuropathy appearance was reported to be 74.3%. In this study, we examined a correlation between GSTP1(342G>A)and ABCC2(1249G>A)of genetic polymorphism. The mean FOLFOX drug dosage was 8.6 times. The first, second and third line treatment was 36, 32 and 9 cases, respectively. Then, the 50% survival duration of each treatment was 801, 360 and 328 days, respectively. These results showed that the first line treatment was highly lengthened the survival duration compared with the second and third line treatment. The response rate was 24.2%, and the lesion control rate was 74.2%. However, some of the toxicities we have seen included the followings: acute nervousness; 74.3%, chronic nervousness; 67.1%, allergic reaction; 26.3%, blood toxicity development; 68.4% and digestive organ symptom; 30.3%. The reasons for change in treatment were due to PD 41.6% and toxicity 51.4%, and that 45.9% of the latter was caused by neuropathy. As for a successful rate of the treatment, the wild type and hetero type of GSTP1, a metabolism enzyme of Oxaliplatin, were 53.3% and 41.7%, respectively. As for a correlation between the dose frequency and GSTP1 SNP was p=0.57, and that a correlation between the dose frequency and ABCC2 was p=0.11. We confirmed that a curative effect of the first line treatment of FOLFOX was high, and that the cases in which the treatment was terminated due to neuropathy prolonged the survival duration. It is important to control the appearance of toxicity in order to continue the treatment. The SNP analysis of the ABCC2 protein may become an index of the treatment for continuation.
Mori
Yasuharu
Y
Dept. of Digestive Surgery, Tokyo Medical University Hospital, Japan.
Katsumata
Kenji
K
Tsuchida
Akihiko
A
Aoki
Tatsuya
T
D003110:Colonic Neoplasms / Q000188:drug therapy; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015996:Survival Rate
D051549:Glutathione S-Transferase pi; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C000715087:ABCC2 protein, human; C496556:GSTP1 protein, human