Optimal methionine-free diet duration for nitrourea treatment: a Phase I clinical trial.
In animal models, methionine (MET) restriction in association with chloroethylnitrosoureas led to a substantial improvement. On this basis, we initiated a Phase I clinical trial of dietary MET restriction in association with chloroethylnitrosourea (cystemustine) treatment for patients with recurrent glioma or metastatic melanoma. Our purpose was 1) to determine the optimal MET-free diet duration for a maximum depletion of plasma MET and 2) to evaluate the feasibility of this association. A total of 10 patients received 4 cycles of 2 wk of an association of a MET-free diet of 1, 2, 3, or 4 consecutive days and cystemustine (60 mg/m(2)). For each cycle, plasma MET concentrations, nutritional status (weight, albumin, prealbumin) and toxicity were measured. Conversely, fed-state concentrations of plasma MET (12 AM) were reduced by dietary MET restriction, with an optimal depletion of 41% at the 1st day of MET-free diet without effect of the extending MET-free diet period. Indeed, we demonstrated the feasibility, that is, good diet acceptability and good tolerance (nutritional status and toxicity), of the association of a MET-free diet and cystemustine treatment. Based on these results, a Phase II clinical trial has been initiated to test the activity of the association of a 1-day MET-free diet with cystemustine treatment.
Durando
Xavier
X
Centre Jean Perrin, Unité de Recherche Clinique, Université Clermont 1, UFR Médecine, Inserm UMR 484, and Centre d'Investigation Clinique, Clermont-Ferrand, France.
Thivat
Emilie
E
Farges
Marie-Chantal
MC
Cellarier
Eric
E
D'Incan
Michel
M
Demidem
Aïcha
A
Vasson
Marie-Paule
MP
Barthomeuf
Chantal
C
Chollet
Philippe
P
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000628:therapy*; D008715:Methionine / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D009752:Nutritional Status; D009837:Oligodendroglioma / Q000378:metabolism / Q000628:therapy*; D010349:Patient Compliance; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; C051263:N'-(2-chloroethyl)-N-(2-(methylsulfonyl)ethyl)-N'-nitrosourea; D008715:Methionine