Efficacy comparisons between the de Gramont regimen or its modifications and the Mayo regimen suggest that the former are no Pacritinib aml less effective (de Gramont et al, 1997a; Andre et al, 2003). Grade 3 or 4 adverse effects were frequently reported in the present series; 45% of the patients treated with the simplified de Gramont regimen and 87% of those treated with the Mayo regimen had at least one grade 3 or 4 adverse effect. These figures are higher (Andre et al, 2003) or approximately similar in frequency (Labianca et al, 1995) as those reported from studies where similar types of chemotherapy have been administered in the adjuvant setting. Use of radiation therapy in rectal cancer, and the patients keeping a diary may have increased the number of reported events in the present series.

We administered 5-FU as true boluses with an approximate injection time of 3min, which may be associated with more adverse events than short (about 15min) infusions (Andre et al, 2001). We also included VAD-related adverse effects, though they were infrequent in comparison to some other series (Carde et al, 1989; Gleeson et al, 1993; Kock et al, 1998). The chemotherapy regimens investigated did not contain irinotecan, capecitabine, or oxaliplatin that are now commonly used to treat colorectal cancer, which is a limitation of the study. The study was not placebo-controlled nor blinded to administration of the dietary supplements, which may or may not have influenced assessment of adverse effects.

To remedy these potential shortcomings, we have initiated a prospective, randomised, multicentre, double blind, placebo-controlled study with a cross-over design where we investigate the effects of Lactobacillus supplementation in conjunction with chemotherapy that contains capecitabine, oxaliplatin, irinotecan, and bevacizumab. We conclude that daily oral administration of L. rhamnosus GG may reduce the frequency of severe 5-FU-based chemotherapy-related diarrhoea, whereas fibre supplementation may be of little benefit. Lactobacillus supplementation may be a practical and well-tolerated Brefeldin_A means to reduce the severity of 5-FU-based chemotherapy-induced diarrhoea, and deserves to be evaluated further. COMPETING INTERESTS TR, AO, PV, MK, IE, and HJ declare no conflict of interest. P? has received an honorarium from Baxter for teaching. MS is an employee at Valio Research center, Valio Ltd., Finland. RK is an employee at Valio Research center and University of Helsinki, Institute of Biomedical Sciences. This is an investigator-initiated and conducted study. Lactobacillus rhamnosus GG capsules were provided free-of-charge for the study by Valio.