A phase II study of bryostatin-1 and paclitaxel in patients with advanced non-small cell lung cancer

Lung Cancer. 2003 Feb;39(2):191-6. doi: 10.1016/s0169-5002(02)00447-6.


Background: Bryostatin-1 is a macrocyclic lactone, which exhibits pleiotropic biological effects via protein kinase C and has shown preclinical synergy with paclitaxel for enhanced tumor cell apoptosis.

Patients and methods: Patients had stage IIIB (pleural effusion)/IV non-small cell lung cancer, measurable disease, performance status 0-2 Eastern Cooperative Oncology Group, adequate organ function, and no prior chemotherapy. Patients received dexamethasone premedication followed by paclitaxel at a dose of 90 mg/m(2) on days 1, 8, and 15 along with bryostatin-1 50 microg/m(2) on days 2, 9, and 16 every 28 days until disease progression. Correlative assays measuring serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and T-lymphocyte numbers were performed based on a previous study showing cytokine induction in vivo by bryostatin-1. Fifteen patients were enrolled.

Results: Thirty cycles of the bryostatin-1 and paclitaxel were delivered with a median of 2 per patient (range 1-4). Myalgia was the predominant non-hematologic toxicity encountered as 3 patients developed grade 4 and 1 patient developed grade 3 myalgia. Four patients were removed from the study during cycle 1 for rapid disease progression or myalgia. Eleven patients could be evaluated for response. Five patients had stable disease, two had a mixed response, and four had progressive disease. Ten patients received second-line chemotherapy after leaving the study. Median survival was 31 weeks (95% confidence interval: 5.4-49.3). Correlative data showed a trend towards decreased plasma IL-6 and TNF-alpha after each cycle of therapy presumably due to the dexamethasone premedication and/or paclitaxel.

Conclusions: This drug combination showed no significant clinical response and was associated with reproducible toxicity. The predominance of myalgia in the absence of elevated serum cytokines suggests a non-inflammatory etiology of this toxicity.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / secondary
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bryostatins
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Glucocorticoids / administration & dosage
  • Humans
  • Interleukin-6 / blood
  • Lactones / administration & dosage
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy*
  • Macrolides
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Premedication
  • Survival Rate
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Bryostatins
  • Glucocorticoids
  • Interleukin-6
  • Lactones
  • Macrolides
  • Tumor Necrosis Factor-alpha
  • bryostatin 1
  • Paclitaxel