Phase II trial of the association of a methionine-free diet with cystemustine therapy in melanoma and glioma

Anticancer Res. 2009 Dec;29(12):5235-40.

Abstract

Background: In a previous phase I clinical trial of dietary methionine (MET) restriction with cystemustine treatment for melanoma or glioma, we determined the optimal MET-free diet duration to be 1 day. On this basis, a phase II clinical trial was initiated to evaluate safety and efficacy of this combination.

Patients and methods: Twenty-two patients (20 with metastatic melanoma and 2 with recurrent gloma) received a median of 4 cycles of the association of a 1-day MET-free diet with cystemustine (60 mg/m(2)) every two weeks.

Results: This association was well tolerated (toxicity and nutritional status). Toxicity remained mainly hematological and consisted of WHO grade 3-4 thrombocytopenia, leucopenia and neutropenia in 36, 27 and 27% of patients respectively. The median disease-free survival was 1.8 months and the median survival was 4.6 months, with 2 long-duration stabilizations. The plasmatic MET depletion obtained was of 40 + or - 31%.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy*
  • Choroid Neoplasms / metabolism
  • Choroid Neoplasms / secondary
  • Choroid Neoplasms / therapy*
  • Combined Modality Therapy
  • Diet*
  • Female
  • Glioma / metabolism
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma / therapy*
  • Methionine / administration & dosage
  • Methionine / deficiency*
  • Middle Aged
  • Neoplasm Staging
  • Nitrosourea Compounds / therapeutic use*
  • Nutritional Status
  • Prognosis
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Nitrosourea Compounds
  • N'-(2-chloroethyl)-N-(2-(methylsulfonyl)ethyl)-N'-nitrosourea
  • Methionine