title: A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma.
abstract: BACKGROUND
  There is no standard first-line therapy for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma and the prognosis remains poor. Our institution conducted a phase I study of oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule. The regimen was tolerated; pharmacodynamic studies revealed no drug interactions, and there was one confirmed response in a gastric cancer patient. We performed a phase II trial in advanced gastric and GEJ adenocarcinoma to determine response rate and response duration.
  
  
  METHODS
  This was a multi-center single treatment arm study involving six sites. Only prior adjuvant therapy was allowed. Patients had ECOG performance status of 0-2, adequate organ function, and were able to tolerate oral medications. All patients received oxaliplatin 60 mg/m(2) intravenously (IV) and irinotecan 50 mg/m(2) IV weekly times 4 weeks with a 2-week rest period. Capecitabine 450 mg bid orally was received on days 1 through 5 every week for 4 weeks, followed by a 2-week rest. Patients were assessed for response after the first two cycles; response duration, overall survival, and adverse events were also recorded. We estimated an improvement in historical response rate by 30% would have clinical meaning.
  
  
  RESULTS
  A total of 39 patients were accrued and all were assessed for toxicity; 30 patients were evaluable for response. The median age was 57.8 years (31-79 years) and 74% were male. Two patients had a complete response, with nine patients achieving a partial response. The total response rate was 28%, with nine patients not evaluable for response. The median response duration was noted at 5.97 months and median overall survival was 8.98 months. There were no grade 5 treatment related events, with all deaths secondary to disease progression. Only five grade 4 events occurred (neutropenia, hyperkalemia, hypokalemia (2), thrombosis/embolism) without grade 4 diarrhea or sensory neuropathy.
  
  
  CONCLUSIONS
  Oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule does induce responses in advanced gastric and GEJ adenocarcinoma. However, the total response rate is modest and not an improvement over other regimens.
authors.affiliation: Developmental Therapeutics Program, Case Comprehensive Cancer Center, Cleveland, OH, USA. Joanna.Brell@UHhospitals.org
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Brell
authors.forename: Smitha S
authors.initials: SS
authors.lastname: Krishnamurthi
authors.forename: Milind
authors.initials: M
authors.lastname: Javle
authors.forename: Joel
authors.initials: J
authors.lastname: Saltzman
authors.forename: Ira
authors.initials: I
authors.lastname: Wollner
authors.forename: Robert
authors.initials: R
authors.lastname: Pelley
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
authors.forename: Belagodu N
authors.initials: BN
authors.lastname: Kantharaj
authors.forename: Mark D
authors.initials: MD
authors.lastname: Schluchter
authors.forename: Linda
authors.initials: L
authors.lastname: Rath
authors.forename: S Percy
authors.initials: SP
authors.lastname: Ivy
authors.forename: Scot C
authors.initials: SC
authors.lastname: Remick
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010166:Palliative Care; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin