Phase I Clinical Trial of Carbetimer

Axel R. Hanauske, Teresa J. Melink, Glenn S. Harman, Gary M. Clark, John B. Craig, Jim M. Koellei, David H. Boldt, Beverly Kantor, Daniel L. Kisner, Gayle Orczyk, David W. Anderson, Edward Paget, Gisele A. Sarosy, Daniel D. Von Hoff

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Carbetimer (carbethimer, N-137, NED-137, carboxyimamidate) is a low molecular weight polyelectrolyte with antitumor activity in a variety of tumor models. This phase I trial evaluated a single dose of carbetimer infused over 1–2 h every 28 days. Forty-three patients received 71 courses of the drug at doses ranging from 180 to 8500 mg/m2. The dose-limiting toxicity was hypercalcemia (serum calcium >12.5 mg/dl) noted in two of three patients at a dose of 8500 mg/m2. Serum calcium levels between 10.5 and 12.5 mg/dl were noted in an additional three patients treated at doses ≥1600 mg/m2. Calcium balance studies in three patients treated at 6500 mg/m2 revealed an increase in urinary cyclic AMP and phosphate excretion after treatment accompanied by a mild elevation of serum parathyroid hormone. Immunological studies in these patients revealed a statistically significant increase in the percentage of peripheral T-helper cells. An increase in the T-helper/suppressor cell ratio was observed in two of the three patients studied. Interleukin 2 production by phytohe-magglutinin-stimulated peripheral mononuclear cells was increased in two of three patients. One patient with a renal cell carcinoma showed a mixed response. The recommended dose for phase II trials as assessed from this study is 6500 mg/m2 as a single dose every 28 days.

Original languageEnglish (US)
Pages (from-to)5353-5357
Number of pages5
JournalCancer Research
Volume48
Issue number18
StatePublished - Sep 1988

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hanauske, A. R., Melink, T. J., Harman, G. S., Clark, G. M., Craig, J. B., Koellei, J. M., Boldt, D. H., Kantor, B., Kisner, D. L., Orczyk, G., Anderson, D. W., Paget, E., Sarosy, G. A., & Von Hoff, D. D. (1988). Phase I Clinical Trial of Carbetimer. Cancer Research, 48(18), 5353-5357.