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: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.forename: Manish A
authors.initials: MA
authors.lastname: Shah
authors.forename: Yelena Y
authors.initials: YY
authors.lastname: Janjigian
authors.forename: Ronald
authors.initials: R
authors.lastname: Stoller
authors.forename: Stephen
authors.initials: S
authors.lastname: Shibata
authors.forename: Margaret
authors.initials: M
authors.lastname: Kemeny
authors.forename: Smitha
authors.initials: S
authors.lastname: Krishnamurthi
authors.forename: Yungpo Bernard
authors.initials: YB
authors.lastname: Su
authors.forename: Allyson
authors.initials: A
authors.lastname: Ocean
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: Bhoomi
authors.initials: B
authors.lastname: Mehrotra
authors.forename: Paul
authors.initials: P
authors.lastname: Ritch
authors.forename: Charles
authors.initials: C
authors.lastname: Henderson
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001707:Biopsy, Needle; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018570:Risk Assessment; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014481:United States
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil