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Cancer Chemotherapy and Pharmacology

, Volume 37, Issue 3, pp 254–258 | Cite as

Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer

  • Karen Hoffman
  • Frankie Ann Holmes
  • Giuseppe Fraschini
  • Laura Esparza
  • Debra Frye
  • Martin N. Raber
  • Robert A. Newman
  • Gabriel N. Hortobagyi
Tricyclic Nucleoside, Phosphate, Triciribine, Metastatic Breast Cancer, Hypertriglyceridemia, Hyperglycemia

Abstract

Triciribine is a purine analogue which inhibits DNA and protein synthesis. We performed two studies to define its activity against metastatic breast cancer. The first study was a phase II study in 14 patients with metastatic breast cancer who had received two or fewer chemotherapy treatments. The treatment schedule was triciribine 20 mg/m2 per day by 24-h infusion (CI) daily for 5 days every 6 weeks as recommended by a previous open phase I trial. When neither response nor toxicity was seen in the phase II trial, we assumed the starting dose was too low for this group of patients with good performance status and repeated the phase I trial in patients with metastatic breast cancer with good performance status. The starting dose was 35 mg/m2 per day using the same 5-day CI schedule, and starting doses were increased in subsequent cohorts of three patients in increments of 5 mg/m2 until toxicity occurred. In the initial (phase II) study, one patient had stable disease for 18 weeks (three courses), the remainder progressed. There were no significant toxic effects. In the subsequent phase I study, ten patients were treated until the study was closed The maximum dose was 40 mg/m2. Two patients died, one each at the 35 and 40 mg/m2 levels, respectively, 3 months and 6 weeks after their last course, one without interveing disease progression. Both had severe hypertriglyceridemia (18- and 21-fold elevation) and severe fatigue. At postmortem examination, one had congestive cardiomyopathy, and the other had severe pancreatitis and hypothyroidism. One patient had severe exacerbation of psoriasis which made her bedridden for more than 30 days. Four patients had hyperglycemia. Plasma pharmacology studies showed erratic drug levels, presumably related to enterohepatic circulation. Postmortem pharmacology studies showed residual drug present as long as 12 weeks after the last dose. We conclude that triciribine is ineffective at all doses tested and at doses of ≥35 mg/m2 has unacceptable toxic effects.

Key words

Tricyclic nucleoside Phosphate Triciribine Metastatic breast cancer Hypertriglyceridemia Hyperglycemia 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Karen Hoffman
    • 1
  • Frankie Ann Holmes
    • 1
  • Giuseppe Fraschini
    • 1
  • Laura Esparza
    • 1
  • Debra Frye
    • 1
  • Martin N. Raber
    • 2
  • Robert A. Newman
    • 2
  • Gabriel N. Hortobagyi
    • 1
  1. 1.Department of Breast and Gynecologic Medical OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Clinical InvestigationThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

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