Oncology Medical News about Oxaliplatin;Cisplatin;Flourouracil and Leucovorin;metastatic gastroesophageal adenocarcinoma

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Pharmacogenetic analyses of a phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil and leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie
Journal of Clinical Oncology, 06/10/09

Goekkurt E et al. - In a study to evaluate the association of germ-line polymorphisms of genes that may impact treatment outcome of platinum and fluorouracil combination chemotherapy in advanced gastric cancer (AGC), these findings underline the hypothesis that germ-line polymorphisms may play an important role in individualizing chemotherapy in AGC and deserve further prospective evaluation in AGC pts.

Methods

Blood samples of 156 pts enrolled onto a phase III study comparing fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin were collected.
Polymorphisms within genes of TS, MTHFR, MTR, OPRT, XPD, ERCC1, XRCC1, XPA, GSTP1, GSTT1, and GSTM1 were genotyped using polymerase chain reaction–based techniques.

Results

Median overall survival (OS) was 11.8 mos and median progression-free survival (PFS) was 5.8 mos.
The TS-3R/+6 haplotype, the GSTT1 deletion polymorphism, and genotypes of OPRT-Gly213Ala and XRCC1-Arg399Gln could be identified as independent predictors of OS.
For PFS analyses, the TS-3R/+6 haplotye and MTR-A2756G were identified as independent positive predictors.
Association between the GSTT1 deletion polymorphism and PFS showed only borderline significance.
Treatment-related hematotoxicity in terms of grade 3/4 leukopenia was lowest among TS-3R/+6 haplotype carriers.
Grade 3/4 neutropenia was directly associated with the MTR-2756G/G genotype, GSTP1-105Ile/Ile genotype, and with the ERCC1-118T/8092C-haplotype.
Significant associations between GSTP1-105Ile/Ile genotype and neurotoxicity and between the XPD-Asn312/751Gln haplotype and nephrotoxicity could be identified.

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