A phase I study of intravenous bryostatin 1 in patients with advanced cancer

J. Prendiville, D. Crowther, N. Thatcher, P. J. Woll, B. W. Fox, A. McGown, N. Testa, P. Stern, R. McDermott, M. Potter, George Pettit

Research output: Contribution to journalArticle

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Abstract

Bryostatin 1 is a novel antitumour agent derived from Bugula neritina of the marine phylum Ectoprocta. Nineteen patients with advanced solid tumours were entered into a phase I study to evaluate the toxicity and biological effects of bryostatin 1. Bryostatin 1 was given as a one hour intravenous infusion at the beginning of each 2 week treatment cycle. A maximum of three treatment cycles were given. Doses were escalated in steps from 5 to 651μg m-2 in successive patient groups. The maximum tolerated dose was 50 hg m-2 Myalgia was the dose limiting toxicity and was of WHO grade 3 in all three patients treated at 65 μg m-2 Flu-like symptoms were common but were of maximum WHO grade 2. Hypotension, of maximum WHO grade 1, occurred in six patients treated at doses up to and including 20 μg m-2 and may not have been attributable to treatment with bryostatin 1. Cellulitis and thrombophlebitis occurred at the bryostatin 1 infusion site of patients treated at all dose levels up to 50 μg m-2 attributable to the 60% ethanol diluent in the bryostatin 1 infusion. Subsequent patients treated at 50 and 65 μg m-2 received treatment with an intravenous normal saline flush and they did not develop these complications. Significant decreases of the platelet count and total leucocyte, neutrophil and lymphocyte counts were seen in the first 24 h after treatment at the dose of 65 μg m-2 Immediate decreases in haemoglobin of up to 1.9g dl-1 were also noted in patients treated with 65 μg m-2 in the absence of clinical evidence of bleeding or haemodynamic compromise. No effect was observed on the incidence of haemopoietic progenitor cells in the marrow. Some patients' neutrophils demonstrated enhanced superoxide radical formation in response to in vitro stimulation with opsonised zymosan (a bacterial polysaccharide) but in the absence of this additional stimulus, no bryostatin 1 effect was observed. Lymphocyte natural killing activity was decreased 2 h after treatment with bryostatin 1, but the effect was not consistently seen 24 h or 7 days later. With the dose schedule examined no antitumour effects were observed. We recommend that bryostatin 1 is used at a dose of 35 to 50 μg m-2 two weekly in phase II studies in patients with malignancies including lymphoma, leukaemia, melanoma or hypemephroma, for which pre-clinical investigations suggest antitumour activity.

Original languageEnglish (US)
Pages (from-to)418-424
Number of pages7
JournalBritish Journal of Cancer
Volume68
Issue number2
StatePublished - Aug 1993

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Neoplasms
Neutrophils
Therapeutics
Bacterial Polysaccharides
bryostatin 1
Thrombophlebitis
Zymosan
Cellulitis
Maximum Tolerated Dose
Myalgia
Lymphocyte Count
Platelet Count
Leukocyte Count
Intravenous Infusions
Superoxides
Antineoplastic Agents
Hypotension
Melanoma
Lymphoma
Appointments and Schedules

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prendiville, J., Crowther, D., Thatcher, N., Woll, P. J., Fox, B. W., McGown, A., ... Pettit, G. (1993). A phase I study of intravenous bryostatin 1 in patients with advanced cancer. British Journal of Cancer, 68(2), 418-424.

A phase I study of intravenous bryostatin 1 in patients with advanced cancer. / Prendiville, J.; Crowther, D.; Thatcher, N.; Woll, P. J.; Fox, B. W.; McGown, A.; Testa, N.; Stern, P.; McDermott, R.; Potter, M.; Pettit, George.

In: British Journal of Cancer, Vol. 68, No. 2, 08.1993, p. 418-424.

Research output: Contribution to journalArticle

Prendiville, J, Crowther, D, Thatcher, N, Woll, PJ, Fox, BW, McGown, A, Testa, N, Stern, P, McDermott, R, Potter, M & Pettit, G 1993, 'A phase I study of intravenous bryostatin 1 in patients with advanced cancer', British Journal of Cancer, vol. 68, no. 2, pp. 418-424.
Prendiville J, Crowther D, Thatcher N, Woll PJ, Fox BW, McGown A et al. A phase I study of intravenous bryostatin 1 in patients with advanced cancer. British Journal of Cancer. 1993 Aug;68(2):418-424.
Prendiville, J. ; Crowther, D. ; Thatcher, N. ; Woll, P. J. ; Fox, B. W. ; McGown, A. ; Testa, N. ; Stern, P. ; McDermott, R. ; Potter, M. ; Pettit, George. / A phase I study of intravenous bryostatin 1 in patients with advanced cancer. In: British Journal of Cancer. 1993 ; Vol. 68, No. 2. pp. 418-424.
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