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

Authors: Ku, G. Y.; Ilson, D. H.; Schwartz, L. H.; Capanu, M.; O'reilly, E.; Shah, M. A.; Kelsen, D. P.; Schwartz, G. K.
Article Title: Phase II trial of sequential paclitaxel and 1 h infusion of bryostatin-1 in patients with advanced esophageal cancer
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/m 2 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. © 2008 Springer-Verlag.
Keywords: adult; cancer survival; clinical article; treatment outcome; aged; middle aged; clinical trial; fatigue; mortality; carcinoma, squamous cell; advanced cancer; cancer combination chemotherapy; diarrhea; dose response; drug dose reduction; drug efficacy; antineoplastic agents; paclitaxel; anorexia; adenocarcinoma; lung toxicity; phase 2 clinical trial; anemia; leukopenia; nausea; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; myalgia; antineoplastic agents, phytogenic; antineoplastic activity; continuous infusion; dyspnea; disease progression; thrombosis; protein kinase c; esophagus cancer; bryostatin 1; esophageal neoplasms; esophageal cancer; lower esophagus sphincter; gastroesophageal cancer; bryostatin-1; sequential injection analysis; bryostatins
Journal Title: Cancer Chemotherapy and Pharmacology
Volume: 62
Issue: 5
ISSN: 0344-5704
Publisher: Springer  
Date Published: 2008-01-01
Start Page: 875
End Page: 880
Language: English
DOI: 10.1007/s00280-008-0677-y
PUBMED: 18270704
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 14" - "Export Date: 17 November 2011" - "CODEN: CCPHD" - "Source: Scopus"
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MSK Authors
  1. Gary Schwartz
    370 Schwartz
  2. Lawrence H Schwartz
    282 Schwartz
  3. Geoffrey Yuyat Ku
    97 Ku
  4. Marinela Capanu
    226 Capanu
  5. Manish Shah
    175 Shah
  6. David H Ilson
    287 Ilson
  7. Eileen O'Reilly
    354 O'Reilly
  8. David P Kelsen
    367 Kelsen