Oral dipyridamole and methotrexate in human solid tumors: a toxicity trial

Celestia S. Higano, Robert B. Livingston

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Dipyridamole (DP) blocks nucleoside salvage by inhibiting uptake at the cell membrane. At the usual oral doses DP has no cytotoxic activity, but when combined with an antimetabolite, it results in synergistic cell kill in vitro. In this study, 45 patients with advanced solid tumors were treated with oral DP and i.v. or i.m. methotrexate (MTX) to define the toxicity of this combination. The DP dose was 75 mg b.i.d. in the first 16 patients, 150 mg b.i.d. in the next 2, and 75 mg q.i.d. in the remaining 27 patients. MTX was given weekly at an initial dose of 10-30 mg/m2 and increased weekly by 5-10 mg/m2 to the maximum tolerable dose (MTD) or a maximum of 60 mg/m2; thereafter that dose was given every other week. DP levels ranged from 2.76 to 11.46 μM, with a mean of 5.67 μM in four patients taking 75 mg q.i.d. The combination of oral DP and MTX was generally well tolrated and did not appear to result in any more myelotoxicity or mucositis than that expected for MTX alone. One patient experienced severe headaches related to DP, ten patients experienced grade 3 or 4 neutropenia and/or thrombocytopenia, and four patients had grade 3 mucositis. Although this trial was not designed as a phase II study, one partial remission was observed in a patient with metastatic pleomorphic adenoma of the parotid gland and seven patients showed significant improvement.

Original languageEnglish (US)
Pages (from-to)259-262
Number of pages4
JournalCancer Chemotherapy And Pharmacology
Volume23
Issue number4
DOIs
StatePublished - Jul 1 1989

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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