Increased hepatic gluconeogenesis: the secret of Lance Armstrong's success.

Enormous amounts of lactic acid are produced during endurance sport by muscle cells. This metabolite is thought responsible for the muscle pain and the fatigue during sport. Its internal removal from the body by enzymatic conversion depends mainly on the capacity of the hepatic gluconeogenesis that converts lactic acid to glucose. The extraordinary sportive results of the racing cyclist Lance Armstrong did us realize that a high capacity of hepatic gluconeogenesis was the basis of his success, because it might have provided him with less pain complaints caused by lactic acid and with an extra source of energy from lactic acid. This enhanced gluconeogenesis can be due to his heavy training program. At the age of 12-13 years he daily swam 10,000m and cycled 32km. In later years as cyclist his training labour was also more than normal. A constitutional increased gluconeogenesis cannot be excluded, because as a boy of 12 years he became already fourth in 1500m free style swimming in a contest for swimmers from whole Texas. The last argument for an increased gluconeogenesis is that Armstrong in October 1996 suffered from an extensively disseminated testicular tumour. This large tumour load caused that in the tumour the oxidative (=aerobic) energy generation changed into a fermentative (=anaerobic) one. This resulted in a high increase of lactic acid that putted up the gluconeogenesis in the liver. We think that this stimulated, high level gluconeogenesis remained high in the following years, when Armstrong restarted cycling, that it provided him with extra energy from lactic acid and with fewer complaints due to the exercise, and that thus this was the basis of his success.

Weekly infusional high-dose fluorouracil (HD-FU), HD-FU plus folinic acid (HD-FU/FA), or HD-FU/FA plus biweekly cisplatin in advanced gastric cancer: randomized phase II trial 40953 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group and the Arbeitsgemeinschaft Internistische Onkologie.

PURPOSE: This multicentric, randomized, two-stage phase II trial evaluated three simplified weekly infusional regimens of fluorouracil (FU) or FU plus folinic acid (FA) and cisplatin (Cis) with the aim to select a regimen for future phase III trials. PATIENTS AND METHODS: A total of 145 patients with advanced gastric cancer where randomly assigned to weekly FU 3,000 mg/m2/24 hours (HD-FU), FU 2,600 mg/m2/24 hours plus dl-FA 500 mg/m2 or l-FA 250 mg/m2 (HD-FU/FA), or FU 2000 mg/m2/24 hours plus FA plus biweekly Cis 50 mg/m2, each administered for 6 weeks with a 1-week rest. The primary end point was the response rate. RESULTS: Confirmed responses were observed in 6.1% (two of 33) of the eligible patients treated with HD-FU, in 25% (12 of 48, including one complete remission [CR]) with HD-FU/FA, and in 45.7% (21 of 46, including four CRs) with HD-FU/FA/Cis. The HD-FU arm was closed after stage 1 because the required minimum number of responses was not met. The median progression-free survival of all patients in the HD-FU, HD-FU/FA, and HD-FU/FA/Cis arm was 1.9, 4.0, and 6.1 months, respectively. The median overall survival was 7.1, 8.9, and 9.7 months, and the survival rate at 1 year was 24.3%, 30.3%, and 45.3%, respectively. Grade 4 toxicities were rare. The most relevant grade 3/4 toxicities were neutropenia in 1.9%, 5.4%, and 19.6%, and diarrhea in 2.7%, 1.9%, and 3.9% of the cycles in the HD-FU, HD-FU/FA, and HD-/FU/Cis arms, respectively. CONCLUSION: Weekly infusional FU/FA plus biweekly Cis is effective and safe in patients with gastric cancer.

19F-magnetic resonance spectroscopy in patients with liver metastases of colorectal cancer treated with 5-fluorouracil.

The purpose of this study was to examine the uptake and metabolism of 5-fluorouracil (5-FU) in human liver metastases. Patients with liver metastases of colorectal cancer were treated with 5-FU (500/600 mg/m)+folinic acid with or without trimetrexate. The clinical application of F-magnetic resonance spectroscopy (MRS) of 5-FU in a random group of patients (n=17) was investigated. MR spectra of all patients showed 5-FU and catabolite resonances, and fluoronucleotides were also seen in seven patients. A correlation was found between maximum levels of 5-FU catabolites as measured by F-MRS and response in a group with larger metastases. However, such correlation was not observed in a group with smaller metastases, probably because of a significant contribution of normal liver tissue to the MR spectra.