Summary
Twenty-four patients with advanced epidermoid carcinoma of the esophagus were treated with trimetrexate (TMTX), a lipid soluble non-classical antifol. Patients were given TMTX 8 mg/m2 intravenously day 1–5 every 28 days. In nine of these patients the dose was escalated to 12 mg/m2 day 1–5 every 28 days. Three patients had a partial response (95% confidence limit 3–32%) with a median response duration of 14 weeks. No hematologic toxicity was documented. Two patients developed moderate stomatitis and only 3 patients experienced any nausea or vomiting. The median survival of all patients is 12 weeks. It is concluded that a higher dose of TMTX should be studied in patients with esophageal cancer in order to assess the true therapeutic value of the agent at a dose closer to the median tolerated dose. A phase II ECOG study using TMTX 12 mg/m2 intravenously day 1–5 every 21 days is currently being conducted.
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References
Earlam R, Cunha-Melo JR: Oesophageal squamous cell carcinoma: I. A critical review of surgery. Br J Surg 67:381–390, 1980
Earlam R, Cunha-Melo JR: Oesophageal squamous cell carcinoma: II. A critical review of radiotherapy. Br J Surg 67:457–461, 1980
Kolaric K, Mqricic Z, Dujmovic I, Roth A: Therapy of advanced esophageal cancer with bleomycin, irradiation and combination bleomycin and irradiation. Tumori 62:255–262, 1976
Engstrom P, Lavin P, Kalssen D: Phase II evaluation of mitomycin and cisplatin in advanced esophageal carcinoma. Cancer Treat Rep 67:713–715, 1983
Ezdinli E, Gelber R, Desai D, Falkson G, Moertel CG, Hahn RG: Chemotherapy of advanced esophageal carcinoma: Eastern Cooperative Oncology Group experience. Cancer 46:2149–2153, 1980
Moertel C, Schutt A, Reitemeier R, Hahn RG: Therapy for gastrointestinal cancer with the nitrosoureas alone in drug combination. Cancer Treat Rep 60:729–732, 1976
Falkson G: Methyl-GAG (NSC 32946) in the treatment of esophageal cancer. Cancer Chemother Rep 55:209–212, 1971
Kelsen DP, Bains MS, Cvitkovic E, Golbey R: Vindesine in the treatment of esophageal carcinoma: A phase II study. Cancer Treat Rep 63:2019–2021, 1979
Coonley C, Bains M, Heelan M, Dukeman M, Kelsen DP: VP-16–213 in the treatment of esophagel cancer: A Phase II trial. Cancer Treat Rep 67:397–398, 1983
Kelsen D, Nanus D, Lipperman R, Eisenberger M: Phase II trial of Ifosfamide (Ifos) in epidermoid carcinoma of the esophagus (ECE): Unexpectedly severe toxicity. (Abstr). Proc Am Soc Clin Oncol 6:A340, 1987
Kamen BA, Eibl B, Cashmore A, Bertino J: Uptake and efficacy of trimetrexate, a non-classical antifolate in methotrexate-resistant cells in vitro. Biochem Pharmacol 33:1697–1699, 1984
Ohnoshi T, Ohnuma T, Takahashi I, Scanion K, Kamen BA, Holland JF: Establishment of methotrexate resistant human acute lymphoblastic leukemia cells in culture and effects of folate antagonists. Cancer Res 42:1655–1560, 1982
Mini E, Moroson BA, Franco CT, Bertino JR: Cytotoxic effects of folate-antagonists against methotrexate-resistant human leukemia lymphoblast CCRF-CEM cell line. Cancer Res 45:325–330, 1985
Broome MG, Johnson RK, Wodinsky I: Biochemical and biological characterization of two new antifols, NSC 127755 and TMQ in comparison with methotrexate. (Abstr). Proc AACR 21:309, 1980
NCI Clinical Brochure: Trimetrexate glucoronate NSC 352122, November, 1983
Warner Lambert: Investigator's Brochure. Trimetrexate glucuronate, 1985
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Alberts, A.S., Falkson, G., Badat, M. et al. Trimetrexate in advanced carcinoma of the esophagus. Invest New Drugs 6, 319–321 (1988). https://doi.org/10.1007/BF00173651
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DOI: https://doi.org/10.1007/BF00173651