Cancer Chemotherapy and Pharmacology

, Volume 62, Issue 5, pp 875–880 | Cite as

Phase II trial of sequential paclitaxel and 1 h infusion of bryostatin-1 in patients with advanced esophageal cancer

  • Geoffrey Y. Ku
  • David H. Ilson
  • Lawrence H. Schwartz
  • Marinela Capanu
  • Eileen O’Reilly
  • Manish A. Shah
  • David P. Kelsen
  • Gary K. Schwartz
Original Article

Abstract

Background

We sought to determine the response rate and toxicity profile of sequential paclitaxel and bryostatin-1, a novel, selective inhibitor of protein kinase C, in patients with advanced esophageal cancer.

Patients and methods

Patients with advanced esophageal and gastroesophageal junction cancer were enrolled. All gave informed consent. They were initially treated with paclitaxel 90 mg/m2 intravenously on Day 1 and bryostatin-1 50 μg/m2 on Day 2 weekly for three consecutive weeks out of four. Because of severe myalgias, dosing was reduced to paclitaxel 80 mg/m2 with bryostatin-1 40 μg/m2 and then to paclitaxel 80 mg/m2 with bryostatin-1 25 μg/m2.

Results

Twenty-four patients were enrolled, with 22 assessable for response. The partial response rate was 27%. 10 patients treated with bryostatin-1 40–50 μg/m2 had a response rate of 40 versus 17% at bryostatin-1 25 μg/m2 (p-value = 0.3). Median time-to-progression was 3.7 months and median survival was 8.3 months. Grade 3/4 myalgias were seen in 50% of patients. Myalgias appeared to be related to bryostatin-1 dose. Because of toxicity, the trial was closed prior to full accrual.

Conclusions

Despite potential anti-tumor activity of this combination in patients with advanced esophageal cancer, further development is not warranted, given the severe toxicity, especially myalgias, that were seen.

Keywords

Bryostatin-1 Esophageal cancer Gastroesophageal cancer Paclitaxel Protein kinase C 

Notes

Acknowledgments

Supported in part by FDA-R01-001826 from the Food and Drug Administration Orphan Drug Program (to GKS).

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Geoffrey Y. Ku
    • 1
  • David H. Ilson
    • 1
  • Lawrence H. Schwartz
    • 2
  • Marinela Capanu
    • 3
  • Eileen O’Reilly
    • 1
  • Manish A. Shah
    • 1
  • David P. Kelsen
    • 1
  • Gary K. Schwartz
    • 1
  1. 1.Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of RadiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Department of Biostatistics and EpidemiologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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