Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma: A study of the US gastric cancer consortium Journal Article

  

Authors:	Shah, M. A.; Janjigian, Y. Y.; Stoller, R.; Shibata, S.; Kemeny, M.; Krishnamurthi, S.; Bernard, Su, Y.; Ocean, A.; Capanu, M.; Mehrotra, B.; Ritch, P.; Henderson, C.; Kelsen, D. P.
Article Title:	Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma: A study of the US gastric cancer consortium
Abstract:	Purpose Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and is associated with significant toxicity. We examined the safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter phase II study. Patients and Methods Previously untreated patients with metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either mDCF (fluorouracil 2,000 mg/m2 intravenously [IV] over 48 hours, docetaxel 40 mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 3, every 2 weeks) or parent DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, and fluorouracil 750 mg/m2 IV over 5 days with granulocyte colony-stimulating factor, every 3 weeks). The study had 90% power to differentiate between 6-month progression-free survival of 26% and 43%, with type I and II error rates of 10% each. An early stopping rule for toxicity was included, defined as grade 3 to 4 adverse event rate > 70% in the first 3 months. Results From November 2006 to June 2010, 85 evaluable patients were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31) closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52% hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI, 34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6 months; P = .007). Conclusion mDCF is less toxic than parent DCF, even when supported with growth factors, and is associated with improved efficacy. mDCF should be considered a standard first-line option for patients with metastatic gastric or GEJ adenocarcinoma. © 2015 American Society of Clinical Oncology. All rights reserved.
Keywords:	adult; controlled study; aged; major clinical study; overall survival; cisplatin; fluorouracil; cancer combination chemotherapy; drug efficacy; drug safety; side effect; treatment duration; metastasis; progression free survival; multiple cycle treatment; neutrophil count; phase 2 clinical trial; anemia; randomized controlled trial; creatinine; creatinine blood level; docetaxel; alanine aminotransferase blood level; aspartate aminotransferase blood level; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; hospitalization; karnofsky performance status; multicenter study; thrombocyte count; alkaline phosphatase blood level; recombinant granulocyte colony stimulating factor; stomach adenocarcinoma; bilirubin blood level; human; male; female; priority journal; article; metastatic gastric adenocarcinoma
Journal Title:	Journal of Clinical Oncology
Volume:	33
Issue:	33
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2015-11-20
Start Page:	3874
End Page:	3879
Language:	English
DOI:	10.1200/JCO.2015.60.7465
PROVIDER:	scopus
PUBMED:	26438119
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84948456752&partnerID=40&md5=42288982d52152eccc7d152b5d3ab3ac
Notes:	Article -- 1 -- Export Date: 7 January 2016 -- 3874 -- Source: Scopus

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