Optimal Methionine-Free Diet Duration for Nitrourea Treatment: A Phase I Clinical Trial

Durando, Xavier; Thivat, Émilie; Farges, Marie‐Chantal; Cellarier, Eric; D’Incan, M.; Demidem, Aïcha; Vasson, Marie‐Paule; Barthomeuf, Chantal; Chollet, Philippe

doi:10.1080/01635580701525877

Cited by 47 publications

(43 citation statements)

References 25 publications

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“…This reduction threshold for plasma MET was consistent with previous reports in healthy men [22] on an oral MET-free diet (49% at 3 h, 60% at 2 days) and in patients with metastatic solid cancer [23]with enteral MET restriction (42% at 4 days). In our previous phase I clinical trial testing the association of a MET-free diet with nitrosourea chemotherapy in metastatic melanoma and recurrent gliomas, the MET-free diet induced a maximal decrease of 55% in the plasma MET concentration 4 h after beginning diet administration without an effect on the extent of the MET-free diet period [24]. Indeed, we confirmed the lack of any cumulative effect of diet on plasma MET concentrations which could be linked to the daily increase in MET level during overnight fasting.…”

Section: Discussionmentioning

confidence: 99%

Dietary Methionine Restriction with FOLFOX Regimen as First Line Therapy of Metastatic Colorectal Cancer: A Feasibility Study

Durando¹,

Farges²,

Buc³

et al. 2010

Oncology

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The methionine (MET) dependency of tumor cells opens interesting perspectives for targeting tumor cells and potentiating chemotherapy treatment, like 5-fluorouracil (5-FU) and platinum compound. Since MET deprivation can individually potentiate the different chemotherapeutic agents used in the 48-hour combined regimen of 5-FU, leucovorin and oxaliplatin (FOLFOX) regimen, we initiated a feasibility study associating dietary MET restriction with the FOLFOX regimen in patients with metastatic colorectal cancer. Objectives: (i) To evaluate the depletion in the plasma MET concentration, and (ii) to assess the feasibility of this combination. Methods: Eleven patients were enrolled in this study. They received a median number of 3 two-week cycles of a MET-free diet (3 consecutive days) and FOLFOX6 regimen. Results: The plasma MET concentration was reduced by dietary MET restriction, with a depletion of 58% on the 1st day of MET-free diet. Indeed, we demonstrated the feasibility and good tolerance (nutritional status and toxicity) of the association of a MET-free diet with the FOLFOX regimen. Despite good compliance to the diet, this study revealed the difficulty of administering this combination during further months. Among the 4 patients evaluable for response, 3 experienced a partial response and 1 patient a disease stabilization.

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Section: Discussionmentioning

confidence: 99%

Dietary Methionine Restriction with FOLFOX Regimen as First Line Therapy of Metastatic Colorectal Cancer: A Feasibility Study

Durando¹,

Farges²,

Buc³

et al. 2010

Oncology

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“…In neither group did we observe a significant change in body weight while on the diet. In comparison, an approximately 40% decrease of plasma Met was previously reported on the first day of a Met-free regimen, which was a more stringent, formulabased Met-free diet [12].…”

Section: Mr Effects On Clinical Patients With Crohn's Diseasementioning

confidence: 94%

“…Data from a phase I clinical trial conducted on 8 patients with metastatic solid tumors by Epner and colleagues indicated for the first time that diet with a reduced Met content is safe and feasible to treat patients with cancer, despite a conclusive lack of sufficient anti-tumor activity [10,11]. A Met-free diet was used in con-junction with other anti-cancer agents in another two Phase I clinical trials [12,13]. Both regimens were found to be relatively feasible and well tolerated, one of which resulted in partial response to the therapy and disease stabilization among 4 evaluated patients [13].…”

Section: Methionine Restriction In Aging and Can-cer Studiesmentioning

confidence: 99%

Methionine Restriction and Modification of Epithelial Tight Junction Barrier Function and Permeability

Wang¹

2012

JEBP

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Abstract:It is well known that caloric restriction leads to an increased longevity by forestalling age-related diseases. Dietary restriction of methionine also renders similar benefits. In this review, we report studies on the effect of methionine restriction on epithelial barrier function in a renal epithelial LLC-PK 1 cell, a rodent gastrointestinal model and a clinical trial using Crohn's patients. In LLC-PK 1 cell culture, a reduction of culture medium methionine by 80% resulted in altered tight junctional claudin composition with improved epithelial barrier function as exemplified by increased transepithelial electrical resistance and decreased paracellular leak to 14 C-D-mannitol. In addition to small but significant reductions in plasma and intracellular colonocyte methionine levels, dietary methionine restriction tightens intestinal epithelium and reduces mannitol permeability in rat colonic, but not ileal tissue. Crohn's patients on methionine-restricted diet reported improved symptoms as demonstrated by a reduced CDAI index, but this diet was not able to significantly reduce the plasma methionine level in patients recruited. An increased urinary lactulose/mannitol ratio was also the result of the regimen in Crohn's patients, suggesting an increased, rather than decreased ileal leakage. Overall, our results showed that reduction in dietary intake of methionine is promising in improving at least some epithelial barriers and this may be through altering tight junctional protein compositions. Methionine restriction might result in contrasting effects depending on the tissue type and possible disease conditions, thus wider range of studies are required.

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“…132 In a Phase I trial with 10 patients with recurrent glioma and metastatic melanoma, the optimal duration of a MET-free diet for maximum depletion of plasma level was determined to be 1 day, leading to a depletion level of 41%. 133 The patients tolerated four cycles of 2 weeks of a MET-free diet in combination with cystemustine treatment. 133 Based on these results, a clinical Phase II trial was initiated with 20 patients with metastatic melanoma and two recurrent glioma receiving four cycles of cystemustine every second week in combination with a MET-free diet.…”

mentioning

confidence: 99%

“…133 The patients tolerated four cycles of 2 weeks of a MET-free diet in combination with cystemustine treatment. 133 Based on these results, a clinical Phase II trial was initiated with 20 patients with metastatic melanoma and two recurrent glioma receiving four cycles of cystemustine every second week in combination with a MET-free diet. 134 The MET plasma level decreased to 53.1% 6 21.8%.…”

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confidence: 99%

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

Neubeck¹,

Seidlitz²,

Kitzler³

et al. 2015

BJR

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Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses .60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression-free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets.

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Optimal Methionine-Free Diet Duration for Nitrourea Treatment: A Phase I Clinical Trial

Cited by 47 publications

References 25 publications

Dietary Methionine Restriction with FOLFOX Regimen as First Line Therapy of Metastatic Colorectal Cancer: A Feasibility Study

Dietary Methionine Restriction with FOLFOX Regimen as First Line Therapy of Metastatic Colorectal Cancer: A Feasibility Study

Methionine Restriction and Modification of Epithelial Tight Junction Barrier Function and Permeability

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

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