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Clinical Studies of Methionine-Restricted Diets for Cancer Patients

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Methionine Dependence of Cancer and Aging

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1866))

Abstract

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.

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Authors and Affiliations

  1. AntiCancer, Inc., San Diego, CA, USA

    Robert M. Hoffman

  2. Department of Surgery, University of California, San Diego, CA, USA

    Robert M. Hoffman

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  1. Robert M. Hoffman
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Correspondence to Robert M. Hoffman .

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  1. AntiCancer, Inc., San Diego, CA, USA

    Robert M. Hoffman

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Hoffman, R.M. (2019). Clinical Studies of Methionine-Restricted Diets for Cancer Patients. In: Hoffman, R. (eds) Methionine Dependence of Cancer and Aging. Methods in Molecular Biology, vol 1866. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8796-2_9

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  • DOI: https://doi.org/10.1007/978-1-4939-8796-2_9

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8795-5

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