Consensus meeting on "Relevance of parenteral vitamin C in acute endothelial dependent pathophysiological conditions (EDPC)".

The 22 supersetnd Hohenheim Consensus Workshop took place in at the University of Stuttgart-Hohenheim. The subject of this conference was vitamin C and its role in the treatment of endothelial dysfunction. Scientists, who had published and reviewed scientific and regulatory papers on that topic were invited, among them basic researchers, toxicologists, clinicians and nutritionists. The participants were presented with eleven questions, which were discussed and answered at the workshop, with the aim of summarising the current state of knowledge. The explicatory text accompanying the short answers was produced and agreed on after the conference and was backed up by corresponding references. The therapeutic relevance of administration of the physiological antioxidant vitamin C in high parenteral doses in Endothelial Dependent Pathophysiological Conditions (EDPC) was discussed. Endothelial dysfunction is defined as including disturbed endothelial dependant relaxation of resistance vessels, breakdown of the microvascular endothelial barrier and/or loss of anti-adhesive function. It occurs in severe burn injury, intoxications, acute hyperglycemia, sepsis, trauma, and ischemic-reperfusion tissue injury and is induced by oxidative stress. Reduced plasma ascorbate levels are a hallmark of oxidative stress and occur in severe burns, sepsis, severe trauma, intoxication, chemotherapy/radiotherapy and organ transplantation. Vitamin C directly enhances the activity of nitric oxide synthase, the acyl CoA oxidase system and inhibits the actions of proinflammatory lipids. There is experimental evidence that parenteral high-dose vitamin C restores endothelial function in sepsis. In vitro, supraphysiological concentrations (> 1mM) of ascorbate restore nitric oxide bioavailability and endothelial function. Only parenterally, can enough vitamin C be administered to combat oxidative stress. There is no evidence that parenteral vitamin C exerts prooxidant effects in humans. Theoretical concerns in relation to competitive interactions between vitamin C and glucose cellular uptake are probably only relevant for oxidised vitamin C (dehydroascorbate).

Epirubicin and ifosfamide in patients with refractory breast cancer and other metastatic solid tumours.

The combination of ifosfamide (IFO) and epirubicin (EPI) has been found to be an effective regimen in the treatment of metastatic tumours and shows remarkable activity in heavily pretreated breast cancer patients. A combination of EPI (35 mg/m2 on days 1 and 2) and IFO (1.8-2.5 g/m2 on days 1-5) was given to 58 patients with refractory breast cancer (n = 23), metastatic sarcomas (n = 15) and other solid tumours (n = 20). Due to extensive prior therapy, the IFO dose had to be adapted to the individual haematological situation. In all, 55 patients were evaluable; we observed 5 complete (CRs) and 16 partial responses (PRs). In addition, 18 patients experienced a minor response (MR) or no change (NC). The median duration of all responses was 6.7 months. Toxicity was generally mild and closely related to previous therapy.

[Sequential treatment of progressive metastatic colorectal cancer with 5-fluorouracil/folinic acid, dipyramidole and mitomycin C]. / Sequentielle Behandlung des progredient metastasierenden kolorektalen Karzinoms mit 5-Fluorouracil/Folinsäure, Dipyramidol und Mitomycin C.

A number of reports have described enhanced therapeutic activity of 5-fluorouracil (5-FU) when combined with high-dose folinic acid (dl-CF). In the present phase-II study 35 patients with colorectal cancer were entered into a first-line chemotherapeutic protocol consisting of dl-CF 200 mg/m2 i.v. push directly followed by 340 mg/m2 5-FU i.v. pushon - days 1-5. Thus far a response rate of 37.5% (12 PR) has been achieved, and minor responses or no change were registered in 43.7% (14 MR or NC), lowering the rate of primary therapeutic failures to 18.8%. Median time to progression was 6.2 months. Toxic side effects consisted mainly of diarrhea, nausea and mucositis. As second-line therapy 5-FU/dl-CF and dipyramidole p.o. were administered to 10 patients with resulting 4 NC. Mitomycin C was given to 9 patients as a third-line regimen with resulting 5 NC for 2-4 months.