BackgroundDysfunctional mitochondrial processes limit malignant cells ability to use energy from fatty acids and ketones. Animal studies using ketogenic diets for cancer show encouraging results. We tested the diet’s safety and feasibility in cancer patients across a broad variety of solid tumors.MethodsWe recruited 17 advanced cancer patients who were not on chemotherapy. They consumed 20 to 40 g of carbohydrates daily with evaluations performed weekly until week 4, then every 4 weeks until 16 weeks. Quality of life questionnaires monitored for tolerability and compliance. Positron emission/computerized tomography was ordered at baseline, 4,8 and 16 weeks. Student t-testing evaluated differences between baseline and last visit scores for quality of life, weight, body mass index, and serum parameters. Correlations between weight loss and serum ketones, glucose, lipids and creatinine were done. Two-tailed unpaired t-testing of the mean weight loss compared responders against non-responders.ResultsEleven out of seventeen enrolled patients were evaluable. Mean age was 65+/- 11.7 years, weight 203 +/- 4.98 lbs. (92 ± 2.3 kgs.) and previous treatment failures was 1.7, +/- 0.97. All lost significant weight with hematologic, biochemical and lipid tests remaining stable. Quality of life scores slightly improved. At 4,8 and 16 weeks, six (54.5 %), five (45.4 %) and four (36 %) patients were stable or improved. We observed no correlations between serum glucose, ketones or lipids. Clinical response did not correlate with ketosis or glycemia. Responders (stable disease or partial responders) lost statistically more weight than non-responders. Dietary compliance was difficult. Only three patients continued dieting past 16 weeks. Out of these, two patients developed brain metastases and were on steroids. They survived 80 and 116 weeks respectively. The third patient underwent residual tumor resection and has no disease at 131 weeks.ConclusionsModified Atkins diets are safe and feasible in advanced cancer. Quality of life was preserved. Patients who lost at least 10 % of their body weight responded the best. Steroid intake affected optimal ketone and glucose levels. Despite this, survival improved in some melanoma and lung cancer patients. Further studies are recommended.Trial registrationClinicaltrials.gov NCT01716468. Registered on September 18, 2012
With the improved survival of patients after liver transplantation, an increase in the incidence of secondary malignancies has been observed. The use of multiple immunosuppressive drugs has been implicated as a strong contributing factor for this increased susceptibility to malignancy, especially cutaneous cancers and lymphoproliferative diseases. With a longer follow-up, we may expect to see a wider variety of malignancies after liver transplantation, probably similar to what we have observed in renal transplant patients. Prevention through changes in lifestyle habits and ongoing surveillance for cancer may improve the timely detection of these malignancies in liver transplant patients, and allow for early institution of effective therapy.
SUMMARYWe present a 57-year-old Caucasian man with hepatocellular carcinoma (HCC) twice achieving complete remission with reduced dose sorafenib. His initial diagnosis of HCC rapidly improved with sorafenib and he achieved a complete biochemical and radiographic response within 7 months. Remission lasted only 5 months but we noted that the timing of his relapse was immediately after he incidentally discontinued clopidogrel. It was restarted and within 5 months of restarting clopidogrel he once again achieved complete remission. The course of his remission was followed and temporal association of sorafenib remission with use of clopidogrel was observed.
BACKGROUND
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