A Randomized Phase 2 and Pilot Pharmacodynamic Trial Investigating the Effect of Salovum™ and SPC-flakes on Dihydropyrimidine Induced Gastrointestinal Toxicity and Tumour Perfusion in Colorectal Cancer

The pyrimidine analogue 5-fluorouracil (5-FU) has a history in oncology for more than 50 years, and is still the backbone in chemotherapy regimens, in particular for gastrointestinal cancer although it is now often substituted with the oral prodrug capecitabine. Since colorectal cancer is the third most common cancer in Europe and the US a great number of patients will be exposed to 5-FU either as part of a curative intent, ie (neo)adjuvant, or with a palliative intention.

One debilitating, and sometimes even life-threatening, toxicity from dihydropyrimidines, e g 5-FU and capecitabine, is gastrointestinal mucositis resulting in, eg severe diarrhoea necessitating in-hospital care including periods of support with iv fluids. The efficacy of current treatment for this adverse effect include iv fluids, loperamide and opioids po and octreotide sc is moderate and new treatment principles or, preferably, ways to prevent such toxicity, are urgently needed. Mucositis is a common adverse effect also from a number of other cancer drugs as well as from radiotherapy.

Cholera induced diarrhoea, as well as other forms of diarrhoea-inducing agents, has been shown to elicit a stimulated, endogenous production of a protein, named "antisecretory factor", ASF. This protein has been chemically characterized in detail. ASF acts by modulating secretion of water and ions but also counteracts inflammatory processes. One of the biologically active peptides of the ASF protein is AF 16, a 16 amino acids long peptide which can easily be synthesized, is chemically very stable, and is therefore used for experimental purposes.

ASF is also produced by hens fed on a diet of fermented grains or a specific diet of sugars and amino acids, leading to an accumulation of the ASF protein in the egg yolk. Spray dried yolk in the form of a powder is commercialized as Salovum registered by the EU authorities as "Food for specific medical purposes", i e is not a drug from a regulatory perspective. Therefore, clinical studies with Salovum (or SPC-flakes, see below) do not need approval from the Medical Products Agency.

Salovum rapidly increase the plasma ASF-concentration. Another way to increase ASF and, thus, to achieve benefit, is to induce its production/conversion by ingestion of oat flakes, specially processed (similar to malting) to contain the proper mix of sugars and amino acids. Such flakes are also commercially available (SPC-flakes) as "Food for specific medical purposes" and has been recommended or considered for a number of secretory pathological conditions, e g for treatment of Mb Meniére.