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Vitamin B12 and folic acid in advanced oesophageal and gastric cancer794was randomized for the addition of vitamins while the study of Vogelzang et al. was not randomized for vitamin suppletion. The discrepancy could also be related to specific effects of folate and vitamin B12 on the efficacy of pemetrexed that do not occur with the cisplatin and gemcitabine combination used in this study[29]. Indeed, in the phase 3 study of Vogelzang et al. the benefit of adding vitamin suppletion was predominantly observed in the group of patients treated with pemetrexed and cisplatin. Moreover, as in our study cisplatin was combined with gemcitabine a potential positive effect of folate suppletion on cisplatin sensitivity (e.g. an increased exposure to free platinum) might have been masked by effects on gemcitabine metabolism as e.g. degradation of gemcitabine to dFdU was increased in supplemented patients. In earlier studies an association between increased gemcitabine deamination and a lower response rate and survival were reported[30]. The formation of the active metabolite of gemcitabine dFdCTP in white blood cells, included as a surrogate biomarker for tissue accumulation, was initially increased. The levels of dFdCTP and the effect of cisplatin are in line with other studies of gemcitabine-cisplatin combination therapy[31]. However, this difference did not persist and may therefore preclude a clinically relevant increase of dFdCTP levels in tissues, which is necessary for an optimal effect of gemcitabine[32]. One can also not exclude that the potentiating effects of vitamin supplementation, as found in patients with mesothelioma, differ between tumor types. The 79A>C polymorphism in the CDA gene and the 667C>T polymorphism in the MTHFR gene were measured in a subgroup of patients. We found no correlation with RR, OS, TTP or severe toxicity although numbers were small and the study was not powered for this analysis. The results of this trial are important for daily practice since vitamin supplement use is very common among patients with cancer[33,34] Reasons for vitamin suppletion include an expected reduced toxicity of chemotherapy, an expected enhanced efficacy of cancer treatment in combination with vitamin use and an expected improvement in general well-being. Complementary medicine is very often not evidence based[35], but in this randomized trial no efficacy benefit was found of vitamin suppletion. In recent years, clinical trials for advanced esophagogastric cancer have focused more on triple-drug regimens. These consist of chemotherapy with tumor-specific targeted therapies, e.g. therapies targeting Her2, c-Met or VEGFR[36-38]. These approaches are likely to be further