Phase I Study of Prolonged Infusion Bryostatin-1 in Patients

Authors:
  • NBNeelesh Bangalore
    Neelesh Bangalore
  • DEDorraya El-Ashry
    Dorraya El-Ashry
  • YFYair Fuxman
    Yair Fuxman
  • MJMichael Johnson
    Michael Johnson
  • BNBrian Norris
    Brian Norris
  • MOMichael Oberst
    Michael Oberst
  • ENElizabeth Ness
    Elizabeth Ness
  • SWSlawomir Wojtowicz-Praga
    Slawomir Wojtowicz-Praga
  • PBPankaj Bhargava
    Pankaj Bhargava
  • NRNaiyer Rizvi
    Naiyer Rizvi
  • SBSaid Baidas
    Said Baidas
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Abstract
Purpose: Bryostatin-1 is a compound known to inhibit protein kinase C expression. Clinical trials have focused on administration schedules ranging from 1 hour to 72 hour infusions. Preclinical data suggest that the down regulation of the target PKC occurs only as long as the drug is being infused. Therefore we performed a phase 1 clinical trial to determine the safety and recommended dose of prolonged infusion Bryostatin-1. Experimental Design: Patients with advanced metastatic cancer were enrolled in this traditional phase 1 clinical trial utilizing prolonged infusion Bryostatin-1. The administration of Bryostatin-1 was initially begun at 96 hours and extended to 14 days. Doses were escalated using the 96 hour infusion time and then duration of infusion was increased. All patients underwent extensive sampling for determination of PKC levels as well as other key biologic end points. The determination of maximum tolerated dose and recommended phase two dose were based on toxicity. Results: 38 patients were...