Phase I trial of pentamethylmelamine in patients with previously treated malignancies

D. A. van Echo, D. F. Chiuten, M. Whitacre, J. Aisner, J. L. Lichtenfeld, P. H. Wiernik

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Pentamethylmelamine (PMM), a demethylated soluble analog of hexamethylmelamine, was given to 35 patients with solid tumors in phase I clinical trial. Thirty patients were given single doses ranging from 80 to 2000 mg/m 2 in a 2-hour infusion every 3 weeks. Once a maximum tolerated dose was defined for this schedule, an additional five new patients plus four patients who had already received PMM were treated on a multiple-dose schedule of PMM given three times a week every Monday, Wednesday, and Friday (M-W-F) for 4 weeks. Dose-limiting toxic effects for the single-dose schedule were in the central nervous system and gastrointestinal tract, manifested by nausea (60%), vomiting (49%), somnolence (37%), depression (6%), and headache (6%). Other toxic effects observed on this schedule included anorexia (34%), diarrhea (7%), and diaphoresis (21%). The toxic effects were first observed in mild form at 400 mg/m 2/dose and became progressively more severe and prolonged with each dose escalation; they were considered intolerable at the 2000-mg/m 2 dose level in all patients treated. The nine patients receiving the multiple-dose schedule were given PMM at a dose of 1000 mg/m 2 three times a week (M-W-F). This level produced dose-limiting nausea and vomiting in all patients so that no patient completed > 3 weeks of treatment on this schedule. One patient developed PMM-related visual hallucinations. PMM produced no hematologic, hepatic, renal, allergic, or acute side effects; no alopecia was observed. Minor tumor regressions of 1 month's duration were seen in two patients, one with pleural mesothelioma and one with a parotid gland tumor. The recommended doses for solid tumor phase II studies are 1500 mg/m 2 given as a 2-hour infusion every 3 weeks and 1000 mg/m 2 given three times a week (M-W-F), repeated at 3-week intervals.

Original languageEnglish (US)
Pages (from-to)1335-1339
Number of pages5
JournalCancer treatment reports
Volume64
Issue number12
StatePublished - 1980

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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