caa a22 4500 465790119 CHVBK 20180323112021.0 cr unu---uuuuu 170327e19900501xx s 000 0 eng 10.1007/BF00177251 doi (NATIONALLICENCE)springer-10.1007/BF00177251 A phase I and pharmacokinetic study of trimetrexate using a 24-hour continuous-infection schedule [Elektronische Daten] [Carmen Allegra, Jean Jenkins, Raymond Weiss, Frank Balis, James Drake, Jay Brooks, Rose Thomas, Gregory Curt] Summary: Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limiting toxicity. Other toxicities included nausea and vomiting, stomatitis, erythema and phlebitis at the site of infusion, rash and skin hyperpigmentation, and elevated serum hepatic enzymes. Two drug-related deaths occurred secondary to leukopenia and sepsis. Twenty-six patients were evaluable for antitumor response. Twenty-one patients had progressive disease, while three patients had disease stabilization. There were two partial responses observed — one in a patient with breast cancer and a second in a patient with nasopharyngeal carcinoma. TMTX pharmacokinetics were studied in 15 patients. The drug had a mean terminal half-life of 13 hours. Steady-state was not achieved during the 24-hour infusions. Only 6% of the parent compound was excreted unchanged in the urine, and CSF levels averaged less than 2% of simultaneously measured plasma levels. A dose of 150 mg/m2 is recommended for phase II trials of TMTX using this 24-hour infusion schedule. Kluwer Academic Publishers, 1990 antifolate nationallicence phase I nationallicence pharmacokinetics nationallicence antimetabolite nationallicence Allegra Carmen Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut Jenkins Jean Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut Weiss Raymond Section of Medical Oncology, Walter Reed Army Medical Center, 20307, Washington D.C., USA aut Balis Frank Pediatric Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut Drake James Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut Brooks Jay Navy-NCI Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut Thomas Rose Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut Curt Gregory Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut Investigational New Drugs Kluwer Academic Publishers 8/2(1990-05-01), 159-166 0167-6997 8:2<159 1990 8 10637 https://doi.org/10.1007/BF00177251 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00177251 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Allegra Carmen Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Jenkins Jean Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Weiss Raymond Section of Medical Oncology, Walter Reed Army Medical Center, 20307, Washington D.C., USA aut NATIONALLICENCE 700 1- Balis Frank Pediatric Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Drake James Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Brooks Jay Navy-NCI Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Thomas Rose Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Curt Gregory Clinical Pharmacology Branch, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA aut NATIONALLICENCE 773 0- Investigational New Drugs Kluwer Academic Publishers 8/2(1990-05-01), 159-166 0167-6997 8:2<159 1990 8 10637 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer