title: Gemcitabine and irinotecan as first-line therapy for carcinoma of unknown primary: results of a multicenter phase II trial.
abstract: Metastatic carcinoma of unknown primary (CUP) has a very poor prognosis, and no standard first-line therapy currently exists. Here, we report the results of a phase II study utilizing a combination of gemcitabine and irinotecan as first-line therapy. Treatment was with gemcitabine 1000 mg/m(2) and irinotecan 75 mg/m(2) weekly times four on a six week cycle (Cohort I). Due to excessive toxicity, the dose and schedule were modified as follows: gemcitabine 750 mg/m(2) and irinotecan 75 mg/m(2) given weekly times three on a four week cycle (Cohort II). The primary endpoint was the confirmed response rate (CR + PR). Secondary endpoints consisted of adverse events based upon the presence or absence of the UDP glucuronosyltransferase 1 family, polypeptide A1*28 (UGT1A1*28) polymorphism, time to progression, and overall survival. Thirty-one patients were enrolled with a median age of 63 (range: 38-94), and 26 patients were evaluable for efficacy. Significant toxicity was observed in Cohort 1, characterized by 50% (7/14) patients experiencing a grade 4+ adverse event, but not in cohort II. The confirmed response rate including patients from both cohorts was 12% (95% CI: 2-30%), which did not meet the criteria for continued enrollment. Overall median survival was 7.2 months (95% CI: 4.0 to 11.6) for the entire cohort but notably longer in cohort II than in cohort I (9.3 months (95% CI: 4.1 to 12.1) versus 4.0 months (95% CI: 2.2 to 15.6)). Gemcitabine and irinotecan is not an active combination when used as first line therapy in patients with metastatic carcinoma of unknown primary. Efforts into developing novel diagnostic and therapeutic approaches remain important for improving the outlook for this heterogeneous group of patients.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00066781.
authors: Mayo Clinic Rochester, Rochester, Minnesota, United States of America.
authors: Shernan G
authors: SG
authors: Holtan
authors: Preston D
authors: PD
authors: Steen
authors: Nathan R
authors: NR
authors: Foster
authors: Charles
authors: C
authors: Erlichman
authors: Fabiola
authors: F
authors: Medeiros
authors: Matthew M
authors: MM
authors: Ames
authors: Stephanie L
authors: SL
authors: Safgren
authors: David L
authors: DL
authors: Graham
authors: Robert J
authors: RJ
authors: Behrens
authors: Matthew P
authors: MP
authors: Goetz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015331:Cohort Studies; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine