Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma Journal Article

Authors: Shah, M. A.; Jhawer, M.; Ilson, D. H.; Lefkowitz, R. A.; Robinson, E.; Capanu, M.; Kelsen, D. P.
Article Title: Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma
Abstract: Purpose: To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. Patients and Methods: Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m2, fluorouracil 400 mg/m2, leucovorin 400 mg/m2 on day 1, fluorouracil 1,000 mg/m2/d x 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m2 on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates. Results: In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). Conclusion: mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively. © 2010 by American Society of Clinical Oncology.
Keywords: adult; clinical article; treatment outcome; treatment response; aged; disease-free survival; middle aged; survival analysis; fatigue; neutropenia; bevacizumab; cisplatin; fluorouracil; diarrhea; drug efficacy; drug safety; hypertension; hypophosphatemia; liver function; side effect; follow up; follow-up studies; neoplasm staging; anorexia; adenocarcinoma; metastasis; progression free survival; multiple cycle treatment; phase 2 clinical trial; bleeding; leukopenia; mucosa inflammation; nausea; neuropathy; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; dehydration; tinnitus; drug administration schedule; continuous infusion; dose-response relationship, drug; docetaxel; febrile neutropenia; hypomagnesemia; hypokalemia; antibodies, monoclonal; thromboembolism; folinic acid; neoplasm metastasis; taxoids; maximum tolerated dose; hand foot syndrome; esophageal adenocarcinoma; alopecia; digestive system perforation; infusions, intravenous; stomach neoplasms; proteinuria; esophagus; esophageal neoplasms; lower esophagus sphincter; dysgeusia; esophagogastric junction; kaplan-meier estimate; hypersensitivity; digestive system fistula; gastroesophageal adenocarcinoma
Journal Title: Journal of Clinical Oncology
Volume: 29
Issue: 7
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2011-03-01
Start Page: 868
End Page: 874
Language: English
DOI: 10.1200/jco.2010.32.0770
PUBMED: 21189380
PROVIDER: scopus
PMCID: PMC3646322
Notes: --- - "Export Date: 23 June 2011" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Marinela Capanu
    206 Capanu
  2. Manish Shah
    174 Shah
  3. David H Ilson
    269 Ilson
  4. David P Kelsen
    332 Kelsen