title: A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia.
abstract: OBJECTIVE
  The incidence of adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia has been rising in the face of limited treatment options for patients with metastatic disease. With the emergence of data to suggest that single agent docetaxel and irinotecan carry antineoplastic effects in this setting, we determined the response rate of these agents when given in combination.
  
  
  METHODS
  Forty-six patients with metastatic adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia were evaluated. Patients received docetaxel 50 mg/m2/d and irinotecan 130 mg/m2/d intravenously at 21-d intervals with a tumor assessment after 2 cycles. Because of unacceptable toxicity among the first 13 patients, dosing was reduced to docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d intravenously at 21-d intervals.
  
  
  RESULTS
  The response rate for the entire cohort was 26% (95% confidence interval: 14%, 41%) with 12 confirmed partial responses. Five of these 12 responses were observed in patients treated at the higher chemotherapy dose. However, because 8 of 13 patients suffered grade 4 neutropenia and fevers, a dose reduction was incorporated into the protocol, and the remainder of the cohort was treated at the lower dose. All except 4 of the 15 observed grade 4 toxicities occurred at the higher dose, and these toxicities included nausea and vomiting, dyspnea, hypotension, dysrhythmias, and diarrhea in addition to neutropenia and fevers. There were no grade 5 toxicities. The median survival for the entire cohort was 7.3 mo.
  
  
  CONCLUSIONS
  The combination of docetaxel and irinotecan provides modest antineoplastic activity among patients with adenocarcinoma of the esophagus, esophagogastric junction, and gastric cardia. Doses of docetaxel 40 mg/m2/d and irinotecan 100 mg/m2/d at 21-d intervals provide an acceptable safety profile, but higher doses appear to result in unacceptable toxicity.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. Jatoi.aminah@mayo.edu
authors.forename: Aminah
authors.initials: A
authors.lastname: Jatoi
authors.forename: Marisa Tria
authors.initials: MT
authors.lastname: Tirona
authors.forename: Steven S
authors.initials: SS
authors.lastname: Cha
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: Roscoe F
authors.initials: RF
authors.lastname: Morton
authors.forename: Suresh
authors.initials: S
authors.lastname: Nair
authors.forename: Carl G
authors.initials: CG
authors.lastname: Kardinal
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stella
authors.forename: James A
authors.initials: JA
authors.lastname: Mailliard
authors.forename: Daniel
authors.initials: D
authors.lastname: Sargen
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002299:Cardia / Q000473:pathology*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D017239:Paclitaxel; D002166:Camptothecin