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Methods Mol Biol. 2019;1866:95-105. doi: 10.1007/978-1-4939-8796-2_9.

Clinical Studies of Methionine-Restricted Diets for Cancer Patients.

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AntiCancer, Inc., San Diego, CA, USA.
Department of Surgery, University of California, San Diego, CA, USA.


Methionine (MET) restriction (MR) has been shown to arrest cancer growth and sensitizes tumors to chemotherapy. MR total parenteral nutrition (MR TPN) with a chemotherapy-containing amino acid solution ("AO-90") (lacking both MET and L-cysteine[CYS]) showed synergistic effects with 5-fluorouracil (5-FU) in tumor-bearing rats and in a Phase I clinical trial with gastrointestinal tract cancers compared to 5-FU in a MET-containing TPN. All gastric cancer patients underwent gastrectomy. Resected tumors in the AO-90 group showed significant reduction of cancer histologically, while almost no effect was seen in the control group. A Phase II clinical trial of dietary MR combined with cystemustine treatment for melanoma or glioma was carried out. Twenty-two patients (20 with metastatic melanoma and 2 with recurrent gloma) received a median of four cycles of the combination of a 1-day MR diet with cystemustine (60 mg/m2) every 2 weeks. This combination was well tolerated (toxicity and nutritional status). The median disease-free survival was 1.8 months and the median survival was 4.6 months, with two long-duration stabilizations. MET depletion in plasma was 40%. In another study, eight patients with a variety of metastatic solid tumors were enrolled in a Phase I clinical trial of a commercially available MR medical food. Participants remained on the experimental diet for an average of 17.3 weeks. Plasma methionine levels fell from 21.6 to 9 μm within 2 weeks, a 58% decline. The only side effect was weight loss of approximately 0.5 kg per week. A feasibility study combining dietary MR with a FOLFOX regimen in patients with metastatic colorectal cancer was carried out. The plasma MET concentration was reduced by dietary MR by 58% on the first day of the MR diet. Among the four patients evaluable for response, three experienced a partial response and one patient had disease stabilization. The results of the above-described clinical trials indicate the clinical potential of MR.


5-FU; 5-Fluorouracil; Cancer; Clinical trial; Gastric cancer; Histological response; MET-restricted TPN; Methionine (MET) dependence; Methionine restriction; Resection; Total parenteral nutrition (TPN)

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