Treatment of patients with metastatic melanoma with bryostatin-1 - A phase II study

R. Gonzalez, S. Ebbinghaus, T. K. Henthorn, D. Miller, Andrew Kraft

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Abstract

Bryostatin-1 is a protein kinase C regulator which has shown antitumour activity against B16 melanoma In animal models. Safety trials revealed this agent to be minimally toxic, thus a phase II trial of bryostatin-1 was conducted to determine its efficacy in patients with melanoma. Eighteen patients with metastatic melanoma, seven of whom had been previously treated, were enrolled in the study. Patients received bryostatin-1 25 μg/m2 intravenously weekly over 1 h for 3 out of 4 weeks. No objective responses were observed. One patient who had not previously received chemotherapy had stable disease for 4 months, and two patients (one previously treated) had a marked decrease In the skin component of their disease. The major toxicity was myalgia (one patient with grade III, two patients with grade II and five patients with grade I), with no grade IV toxicities reported. To indirectly evaluate the stimulation of protein kinase C, a sensitive assay that measures the upregulation of the activated form of CD62 (glycoprotein IIb/IIIa) on platelets was performed. There was a statistically significant upregulation of this antigen 1 h after bryostatin-1 therapy. A bioassay based on the ability of bryostatin-1 to bind protein kinase C was used to measure bryostatin-1 levels in serum. This assay showed that bryostatin-1 has a volume of distribution of 2.1 l/m2, an elimination clearance of 32.9 ml/min per m2 and a half-life of 43.9 min. In conclusion, this phase II trial demonstrates that, although it is relatively non-toxic, bryostatin-1 therapy had minimal activity in metastatic melanoma.

Original languageEnglish (US)
Pages (from-to)599-606
Number of pages8
JournalMelanoma Research
Volume9
Issue number6
Publication statusPublished - 1999
Externally publishedYes

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Keywords

  • Bryostatin-1
  • Metastatic melanoma
  • Pharmacology
  • Platelet activation

ASJC Scopus subject areas

  • Cancer Research
  • Dermatology

Cite this

Gonzalez, R., Ebbinghaus, S., Henthorn, T. K., Miller, D., & Kraft, A. (1999). Treatment of patients with metastatic melanoma with bryostatin-1 - A phase II study. Melanoma Research, 9(6), 599-606.