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Vitamin B12 and folic acid in advanced oesophageal and gastric cancer774Table 3. CDA and MTHFR gene polymorphisms in relation to outcome and toxicity. Polymorphisms in the gene for CDA were measured in 37 patients. The AA variant was found in 22 patients, the CC variant in 7 patients and AC variant in 8 patients. Polymorphisms in the gene for MTHFR were measured in 20 patients. The TT variant was found in 2 patients, the CC variant in 6 patients and CT variant in 12 patients. Abbreviations: OS, overall survival (median months); TTP, time to progression (median months); RR, response rate (%); PR, partial response; CR, complete response; SD, standard deviation.AAn=22CCn=7ACn=8TTn=2CCn=6CTn=12Clinical parameterOS (months) 7.8 (SD 9.1) 17.3 (SD 13.7)10.1 (SD 3.1) 11.0 (SD 12.4)5.0 (SD 19.3) 9.8 (SD 11.0)TTP (months) 5.5 (SD 12.9) 9.0 (SD 8.6) 6.8 (SD 2.0) 10.5 (-) 1.9 (SD 12.8) 6.4 (SD 9.0)PR/CR n=8 n=3 n=5 n=1 n=1 n=6RR (%) 36 43 63 50 17 50Grade 3 toxicityn=12 (55%) n=4 (57%) n=5 (63%) n=1 (50%) n=3 (50%) n=6 (50%)Grade 4 toxicity- - N=1 (13%) - - -DiscussionIn this study we demonstrate that the combination of gemcitabine and cisplatin can be considered an effective palliative chemotherapeutic regime in patients with AEGC. The median combined OS of 9.2 months and TTP of 5.4 months in our study is comparable with the currently commonly used first line palliative chemotherapy regimens for AEGC. The current standard first line palliative chemotherapy for AEGC consists of triplet chemotherapy regimens such as EOX (epirubicin, oxaliplatin and capecitabine, OS/PFS 11.2/7.0 months), ECX (epirubicin, cisplatin, capecitabine, OS/PFS 9.9/6.7 months) or EOF (epirubicin, oxaliplatin and fluorouracil, OS/PFS 9.3/6.5 months)[22] or doublet therapies (fluorouracil, leucovorin in combination with oxaliplatin or cisplatin, OS/PFS resp. 10.7/5.8 vs. 8.8/3.9 months)[23], or capecitabine and oxaliplatin, OS 8 months[24]. A recent meta-analysis showed a limited survival benefit of triplet chemotherapy with an increased risk of toxicity when compared to doublet chemotherapy[25]. Cisplatin and gemcitabine have a different side effect profile compared with oxaliplatin based chemotherapy regimens. Cisplatin is associated with a higher incidence of grade 3 to 4 neutropenia, alopecia, thromboembolism, and renal dysfunction while peripheral neuropathy and diarrhea is a more frequent side effect of oxaliplatin [26,27]. The intravenous administration route of cisplatin and