title: Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
abstract: BACKGROUND
  The value of second-line therapy for metastatic gastric cancer is unclear. So far there are no randomised phase III data comparing second-line chemotherapy to best supportive care (BSC). In this prospective, multicenter, open label, randomised phase III study we compared irinotecan to BSC to evaluate the impact on survival of second-line chemotherapy.
  
  
  METHODS
  Eligible patients (pts) had metastatic or locally advanced gastro-oesophageal junction or gastric adenocarcinoma, objective tumour progression during or within 6months after first-line chemotherapy and ECOG performance status 0-2. Stratification for time of progression after first-line therapy, ECOG PS and pretreatment secured even distribution of important prognostic factors.
  
  
  METHODS
  Arm A: Irinotecan 250mg/m(2)q3w (first cycle) to be increased to 350mg/m(2), depending on toxicity. Arm B: BSC.
  
  
  RESULTS
  Between 10/2002 and 12/2006 40 pts were randomised. The study was closed prematurely due to poor accrual. Responsefor arm A (19 pts evaluable): No objective responses, SD 53%, PD 47%. Improvement of tumour related symptoms: Arm A 50% of pts, arm B 7%. Overall Survival: (all events in 40 pts have occurred): The hazard ratio for death was reduced to 0.48 (95%CI 0.25-0.92) in the irinotecan-arm (p=0.012). Median survival arm A: 4.0months (95% CI 3.6-7.5), arm B: 2.4months (95% CI 1.7-4.9).
  
  
  CONCLUSIONS
  Irinotecan as second-line chemotherapy significantly prolongs overall survival compared to BSC in the studied pts. Second-line chemotherapy can now be considered as a proven treatment option for metastatic or locally advanced gastric cancer.
  
  
  BACKGROUND
  The study was supported by a research grant from Aventis and Pfizer.
authors: Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie, Augustenburger Platz 1, 13353 Berlin, Germany. peter.thuss@charite.de
authors: Peter C
authors: PC
authors: Thuss-Patience
authors: Albrecht
authors: A
authors: Kretzschmar
authors: Dmitry
authors: D
authors: Bichev
authors: Tillman
authors: T
authors: Deist
authors: Axel
authors: A
authors: Hinke
authors: Kirstin
authors: K
authors: Breithaupt
authors: Yasemin
authors: Y
authors: Dogan
authors: Bernhard
authors: B
authors: Gebauer
authors: Guido
authors: G
authors: Schumacher
authors: Peter
authors: P
authors: Reichardt
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005858:Germany; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin