Phase I Study of Tricyclic Nucleoside Phosphate Using a Five-Day Continuous Infusion Schedule

Lynn G. Feun, Niramol Savaraj, Gerald P. Bodey, Katherine Lu, Boh Seng Yap, Jaffer A. Ajani, M. Andrew Burgess, Robert S. Benjamin, Eugene McKelvey, Irwin Krakoff

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

A Phase I trial of tricyclic nucleoside phosphate (1,4,5,6,8-pentaazaacenaphthylene-3-amino-1,5-dihydro-5-methyl-1-β-D-ribo furanosyl 5'-phosphate ester; NSC 280594) was conducted using a 5-day continuous infusion schedule. Thirty-seven patients with advanced cancer were entered on the study, of whom 33 patients were evaluable for response and toxicity. Dose levels ranged from 10 mg/sq m/day x 5 days to 40 mg/sq m/day x 5 days. Initially, courses were repeated every 3 to 4 weeks. As cumulative toxicity became manifested, the interval between courses was changed to every 6 weeks. Major toxicities included hyperglycemia, hepatotoxicity, and thrombocytopenia. Patients with a prior history of diabetes mellitus, extensive radiation therapy, or significant liver metastases were prone to severe toxicity. Other toxicities noted were nausea and vomiting, abdominal discomfort, anemia, and reduction in serum calcium, phosphorus, and albumin levels. Rare side effects included hypertriglyceridemia, hyperamylasemia, diarrhea, and stomatitis. Antitumor activity observed include improvement in s.c. metastases in a patient with thyroid carcinoma, stabilization of disease in a patient with mesothelioma, and mixed responses in three patients (colon cancer, sarcoma, and tonsillar squamous cell cancer). Recommended schedule for Phase II studies is 20 mg/sq m/day for 5 days every 6 weeks.

Original languageEnglish (US)
Pages (from-to)3608-3612
Number of pages5
JournalCancer Research
Volume44
Issue number8
StatePublished - Aug 1 1984
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Feun, L. G., Savaraj, N., Bodey, G. P., Lu, K., Yap, B. S., Ajani, J. A., Burgess, M. A., Benjamin, R. S., McKelvey, E., & Krakoff, I. (1984). Phase I Study of Tricyclic Nucleoside Phosphate Using a Five-Day Continuous Infusion Schedule. Cancer Research, 44(8), 3608-3612.