Abstract
Bryostatin-1 is a macrocyclic lactone thathas been shown to modulate Protein Kinase Cactivity and has demonstrated antitumoractivity in vitro and in vivo. Fifteen patients with metastatic orrecurrent squamous cell carcinoma of thehead and neck were treated withbryostatin-1 at a dose of 25 mcg/m2 bycontinuous intravenous infusion over 24hours once weekly for three weeks followedby a break week to complete a four-weekcycle. There were no major objectiveresponses in the 14 evaluable patients. One patient with nasopharynx cancer haddisease stabilization for 4 months prior tobeing removed from the study due to medicalissues. This clinical benefit correspondedto a radiographic decrease in metabolicactivity on positron emission tomograpy(PET) scan as well as molecular evidence oftumor apoptosis in a poly[ADP-ribose]polymerase (PARP) cleavage assay. Bryostatin-1 is not recommended for use asa single agent for the treatment ofsquamous cell head and neck cancer. Further investigation is warranted todetermine the strength of the correlationbetween bryostatin-1 activity and PARPcleavage as a surrogate molecular marker ofapoptosis.
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References
Philip PA, Zonder JA: Pharmacology and clinical experience with bryostatin 1: a novel anticancer drug. Expert Opin Investig Drugs 8(12): 2189–2199, 1999
Hofmann J: Modulation of protein kinase C in antitumor treatment. Rev Physiol Biochem Pharmacol 142: 1–96, 2001
Philip PA, Rea D, Thavasu P, Carmichael J, Stuart NS, Rockett H, Talbot DC, Ganesan T, Pettit GR, Balkwill F, Harris AL: Phase I study of bryostatin 1: assessment of interleukin 6 and tumor necrosis factor alpha induction in vivo. The Cancer Research Campaign Phase I Committee. J Natl Cancer Inst 85(22): 1812–1818, 1993
Propper DJ, Macaulay V, O'Byrne KJ, Braybrooke JP, Wilner SM, Ganesan TS, Talbot DC, Harris AL: A phase II study of bryostatin 1 in metastatic malignant melanoma. Br J Cancer 78(10): 1337–1341, 1998
Prendiville J, Crowther D, Thatcher N, Woll PJ, Fox BW, McGown A, Testa N, Stern P, McDermott R, Potter M, Pettit GR: A phase I study of intravenous bryostatin 1 in patients with advanced cancer. Br J Cancer 68(2): 418–424, 1993
Jayson GC, Crowther D, Prendiville J, McGown AT, Scheid C, Stern P, Young R, Brenchley P, Chang J, Owens S, Pettit GR: A phase I trial of bryostatin 1 in patients with advanced malignancy using a 24 hour intravenous infusion. Br J Cancer 72(2): 461–468, 1995
Miller AB, Hoogstraten B, Staquet M, Winkler A: Reporting results of cancer treatment. Cancer 47: 207–214, 1981
Simon R: Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10(1): 1–10, 1989
Koutcher JA, Motwani M, Zakian KL, Li XK, Matei C, Dyke JP, Ballon D, Yoo HH, Schwartz GK: The in vivo effect of bryostatin-1 on paclitaxel-induced tumor growth, mitotic entry, and blood flow. Clinical Cancer Res 6(4): 1498–1507, 2000
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Pfister, D.G., McCaffrey, J., Zahalsky, A.J. et al. A Phase II Trial of Bryostatin-1 in Patients with Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck. Invest New Drugs 20, 123–127 (2002). https://doi.org/10.1023/A:1014449309165
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DOI: https://doi.org/10.1023/A:1014449309165