Serum methionine depletion without side effects by methioninase in metastatic breast cancer patients.

摘要: The growth dependence of human tumors on elevated levels methionine has been shown in preclinical vitro and vivo studies to be a frequently occurring, highly effective, tumor-selective therapeutic target. High purity endotoxin-free methioninase was produced from Pseudomonas putida order develop anti-methionine chemotherapy targeting tumors. A pilot Phase I clinical trial initiated determine toxicity, the pharmacokinetics methionine-depletion maximum tolerated dose. two hour i.v. infusion 5,000 units (0.4 g) 10,000 (0.8 ten 20,000 (1.6 administered patient-1, patient-2, patient-3, respectively. All patients had advanced breast cancer. Blood urine samples were obtained at frequent intervals between 0 24 hours. toxicity evaluations carried out according FDA criteria. Pharmacokinetics data for both serum. No acute observed all criteria measured patient-2 patient-3. depletion serum started within 30 minutes infusion, maintained 4 hours after completed patient-1 patient-2. lowest 35% 19% pretreatment level, respectively, Patient-3 received without any signs side effects. as high 50% level subsequent 6 infusion. Methionine depleted over 200-fold 23.1 microM 0.1 by 10-hour whatsoever results 1 suggested that is safe effectively depletes Clinical are continuing length time complete can tolerated.