title: Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer.
abstract: OBJECTIVE
  This phase II, multicenter, open-label, single-arm study evaluated the efficacy and safety of irinotecan and gemcitabine as combination chemotherapy for previously untreated patients with unresectable or metastatic pancreatic cancer.
  
  
  METHODS
  Patients received repeated 21-day cycles at starting doses of gemcitabine 1,000 mg/m(2) over 30 minutes followed immediately by irinotecan 100 mg/m(2) over 90 minutes, both given intravenously on days 1 and 8. Patients were evaluated for objective tumor response, changes in the serum tumor marker CA 19-9, time to tumor progression (TTP), survival, and safety.
  
  
  RESULTS
  Forty-five patients were treated. Eleven patients (24%) had 50% or greater reductions in tumor area. These were confirmed one cycle later in nine patients (response rate, 20%; 95% confidence interval, 8% to 32%). Among 44 patients with baseline CA 19-9 determinations, CA 19-9 decreased during therapy in 22 patients (50%) and was reduced by 50% or more in 13 patients (30%). Median TTP was 2.8 months (range, 0.3 to 10.8 months). There were significant (P <.001) correlations between proportional changes in CA 19-9 and radiographic changes in tumor area with regard to extent of change (r =.67), timing of minimum on-study values (r =.85), and tumor progression (r =.89). Median survival was 5.7 months (range, 0.4 to 19.4+ months), and the 1-year survival rate was 27%. Severe toxicities were uncommon and primarily limited to grade 4 neutropenia (2%), grade 4 vomiting (2%), and grade 3 diarrhea (7%).
  
  
  CONCLUSIONS
  Irinotecan/gemcitabine is a new combination that offers encouraging activity in terms of radiographic and CA 19-9 response and notable 1-year survival in pancreatic cancer. The regimen was well tolerated, with minimal grade 3 and 4 toxicities and excellent maintenance of planned dose-intensity.
authors.affiliation: H. Lee Moffitt Cancer Center, University of South Florida, Gastrointestinal Program Office, Tampa, FL 33612, USA. rochalcm@moffitt.usf.edu
authors.forename: Caio Max S
authors.initials: CM
authors.lastname: Rocha Lima
authors.forename: Diane
authors.initials: D
authors.lastname: Savarese
authors.forename: Howard
authors.initials: H
authors.lastname: Bruckner
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Dudek
authors.forename: John
authors.initials: J
authors.lastname: Eckardt
authors.forename: John
authors.initials: J
authors.lastname: Hainsworth
authors.forename: Furhan
authors.initials: F
authors.lastname: Yunus
authors.forename: Eric
authors.initials: E
authors.lastname: Lester
authors.forename: William
authors.initials: W
authors.lastname: Miller
authors.forename: Wayne
authors.initials: W
authors.lastname: Saville
authors.forename: Gary L
authors.initials: GL
authors.lastname: Elfring
authors.forename: Paula K
authors.initials: PK
authors.lastname: Locker
authors.forename: Linda D
authors.initials: LD
authors.lastname: Compton
authors.forename: Langdon L
authors.initials: LL
authors.lastname: Miller
authors.forename: Mark R
authors.initials: MR
authors.lastname: Green
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D011859:Radiography; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D003841:Deoxycytidine; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine