PHASE-1 STUDY OF TRICYCLIC NUCLEOSIDE PHOSPHATE USING A 5-DAY CONTINUOUS INFUSION SCHEDULE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (8) , 3608-3612
Abstract
A Phase I trial of tricyclic nucleoside phosphate (1,4,5,6,8-pentaazaacenaphthylene-3-amino-1,5-dihydro-5-methyl-1-.beta.-D-ribofuranosyl 5''-phosphate ester: NSC 280594) was conducted using a 5-day continuous infusion schedule. Patients (37) with advanced cancer were entered on the study, of whom 33 patients were evaluated for response and toxicity. Dose levels ranged from from 10 mg/m2 per day .times. 5 days to 40 mg/m2 per day .times. 5 days. Initially, courses were repeated every 3-4 wk. As cumulative toxicity became manifested, the interval between courses was changed to every 6 wk. 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 Ca, P and albumin levels. Rare side effects included hypertriglyceridemia, hyperamylasemia diarrhea and stomatitis. Antitumor activity observed included improvement in s.c. metastases in a patient with papillary thyroid carcinoma, stabilization of disease in a patient with mesothelioma and mixed responses in 3 patients (colon cancer, sarcoma and tonsillar squamous cell cancer). Recommended schedule for Phase II studies is 20 mg/m2 per day for 5 days every 6 wk.

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