Phase II Trial of Trimetrexate in Patients with Advanced Soft-tissue Sarcoma

Overview

Journal Cancer Chemother Pharmacol

Specialty Oncology

Date 1991 Jan 1

PMID 1830249

Citations 2

Authors

J D Licht

R GONIN

K H Antman

Affiliations

Soon will be listed here.

Abstract

Trimetrexate, a lipophilic, 2,4-diaminoquinazoline derivative of methotrexate, enters cells by passive diffusion rather than via a transport system. Trimetrexate has shown promising activity in animal model systems. A total of 16 patients with metastatic soft-tissue sarcoma who had received only one prior chemotherapy regimen were treated with trimetrexate (8 mg/m2 given intravenously daily for 5 days) every 3 weeks. Treatment-related toxicity included greater than or equal to grade 2 neutropenia (8/16), thrombocytopenia (3/16), mucositis (4/16) and skin rash (3/16). No partial or complete responses were observed in 15 evaluable patients (95% confidence interval for true response rate, 0-22%) Six subjects showed stabilization of disease for periods ranging from 2 to 9 months. At this dose and on this schedule, trimetrexate appears to have little activity against refractory soft-tissue sarcomas.

Citing Articles

Phase II Trial of Dolastatin-10, a Novel Anti-Tubulin Agent, in Metastatic Soft Tissue Sarcomas.

von Mehren M, Balcerzak S, Kraft A, Edmonson J, Okuno S, Davey M Sarcoma. 2008; 8(4):107-11.

PMID: 18521404 PMC: 2395616. DOI: 10.1155/2004/924913.

From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates.

Walling J Invest New Drugs. 2005; 24(1):37-77.

PMID: 16380836 DOI: 10.1007/s10637-005-4541-1.

References

Diddens H, Niethammer D, Jackson R . Patterns of cross-resistance to the antifolate drugs trimetrexate, metoprine, homofolate, and CB3717 in human lymphoma and osteosarcoma cells resistant to methotrexate. Cancer Res. 1983; 43(11):5286-92. View

Lin J, Cashmore A, Baker M, Dreyer R, Ernstoff M, Marsh J . Phase I studies with trimetrexate: clinical pharmacology, analytical methodology, and pharmacokinetics. Cancer Res. 1987; 47(2):609-16. View

Weiss R, James W, Major W, Porter M, Allegra C, Curt G . Skin reactions induced by trimetrexate, an analog of methotrexate. Invest New Drugs. 1986; 4(2):159-63. DOI: 10.1007/BF00194596. View

Jolivet J, Chabner B . Intracellular pharmacokinetics of methotrexate polyglutamates in human breast cancer cells. Selective retention and less dissociable binding of 4-NH2-10-CH3-pteroylglutamate4 and 4-NH2-10-CH3-pteroylglutamate5 to dihydrofolate reductase. J Clin Invest. 1983; 72(3):773-8. PMC: 1129242. DOI: 10.1172/JCI111048. View

Bertino J, Sawicki W, Moroson B, Cashmore A, Elslager E . 2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline (tmq), a potent non-classical folate antagonist inhibitor--I effect on dihydrofolate reductase and growth of rodent tumors in vitro and in vivo. Biochem Pharmacol. 1979; 28(12):1983-7. DOI: 10.1016/0006-2952(79)90655-5. View