Clinical studies with MTA
| Autor: | JM Walling, AH Calvert |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Cancer Research Guanine medicine.drug_class Antineoplastic Agents Pemetrexed Pharmacology Antimetabolite Thymidylate synthase Drug Administration Schedule chemistry.chemical_compound Clinical Trials Phase II as Topic Thymidylate synthase inhibitor Glutamates Neoplasms medicine Mucositis Humans Aged Aged 80 and over biology Clinical Trials Phase I as Topic business.industry Middle Aged medicine.disease Gemcitabine Oncology chemistry Antifolate biology.protein Methotrexate Female business medicine.drug Research Article |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | MTA (LY231514), a multi-targeted antifolate, is a classical antifolate undergoing intracellular polyglutamation. Polyglutamated MTA is a potent thymidylate synthase (TS) inhibitor and inhibits other folate-dependent enzymes, including dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. Multifocal antifolates may overcome antifolate resistance, but it is not known whether the anti-tumour activity of MTA depends on its TS inhibition, its primary locus of action, or whether other loci contribute. MTA was examined in three phase I trials using different schedules: a 10-min i.v. infusion given once every 3 weeks, once weekly for 4 weeks every 6 weeks or daily for 5 days every 3 weeks. Dose-limiting toxicities were neutropenia and thrombocytopenia. Other consistently seen side-effects, which were manageable, included mucositis, skin rashes and transient elevations of transaminases. Toxicity was highly schedule dependent: the recommended dose for the 3-weekly schedule (600 mg m(-2)) was 30 times that for the daily x 5 schedule (4 mg m(-2)day(-1)). The 3-weekly dosing schedule was chosen for phase II evaluation. Phase II trials are underway to investigate the activity and toxicity of MTA in several tumour types, including colorectal, pancreas, breast, bladder and non-small-cell lung cancer (NSCLC) Further phase I trials will investigate MTA in combination with other agents, including gemcitabine, cisplatin, 5-fluorouracil and folate. Preliminary phase II trials results are encouraging; responses were seen in colorectal, pancreas, NSCLC and breast cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|