title: Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial.
abstract: OBJECTIVE
  To compare the results of empiric first-line therapy with paclitaxel/carboplatin/etoposide (PCE) versus gemcitabine/irinotecan, both followed by single-agent gefitinib, in patients with carcinoma of unknown primary site.
  
  
  METHODS
  Patients with previously untreated carcinoma of unknown primary site were randomized to receive either PCE or gemcitabine/irinotecan. Responding and stable patients continued treatment for 4 to 6 cycles. Patients with no evidence of tumor progression at that time received single-agent gefitinib until tumor progression. The trial was designed to detect an improvement in the 2-year survival rate from 20% to 30%.
  
  
  RESULTS
  Between September 2003 and July 2008, 198 patients entered this multicenter, community-based trial. Because of slow accrual, the trial was stopped short of its target accrual of 320 patients. Clinical characteristics were comparable for patients receiving PCE (N = 93) and gemcitabine/irinotecan (N = 105). PCE and gemcitabine/irinotecan produced similar 2-year survival (15% vs. 18%), median survival (7.4 months vs. 8.5 months), median progression-free survival (3.3 months vs. 5.3 months), and response rate (18% vs. 18%). Grade 3/4 neutropenia, thrombocytopenia, anemia, febrile neutropenia, and red blood cells transfusions were more common with PCE; diarrhea was more common with gemcitabine/irinotecan. The median duration of gefitinib maintenance was 3 months, suggesting no role as a maintenance therapy in this setting.
  
  
  CONCLUSIONS
  The PCE and gemcitabine/irinotecan regimens have comparable efficacy in the first-line treatment of patients with carcinoma of unknown primary site. Gemcitabine/irinotecan is the preferable regimen, due to its favorable toxicity profile. However, the moderate efficacy of both regimens underscores the need for novel treatment approaches in this patient population.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN, USA. jhainsworth@tnonc.com
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Bobby L
authors.initials: BL
authors.lastname: Clark
authors.forename: Dianna
authors.initials: D
authors.lastname: Shipley
authors.forename: Dana S
authors.initials: DS
authors.lastname: Thompson
authors.forename: Cynthia
authors.initials: C
authors.lastname: Farley
authors.forename: Kimberly
authors.initials: K
authors.lastname: West-Osterfield
authors.forename: Cassie M
authors.initials: CM
authors.lastname: Lane
authors.forename: Terrence
authors.initials: T
authors.lastname: Cescon
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Bury
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D005047:Etoposide; D000077146:Irinotecan; D016190:Carboplatin; D017239:Paclitaxel; D002166:Camptothecin; D000093542:Gemcitabine