title: Comparison of gemcitabine combined with targeted agent therapy versus gemcitabine monotherapy in the management of advanced pancreatic cancer.
abstract: OBJECTIVE
  Targeted therapy has brought great clinical benefits for patients with multiple solid tumors, but its effects in patients with locally advanced/metastatic pancreatic cancer (LA/MPC) are disputed. This systematic evaluation compared the efficacy and safety profiles of gemcitabine combined with targeted agents (GEM + TA) versus gemcitabine administered as monotherapy or combined with placebo (GEM ± PLC) in LA/MPC patients.
  
  
  METHODS
  PubMed and EMBASE were searched for relevant randomized controlled trials published on or before April 30, 2013. The primary end points were overall survival (OS) and progression-free survival (PFS); the secondary end points were 1-year survival rate, objective response rate (ORR), and toxicity rates (TRs), defined as the prevalence of grade 3/4 adverse events. The systematic evaluation was performed by using Review Manager version 5.1.7.
  
  
  RESULTS
  A total of 10 randomized controlled trials involving 3899 patients (2195 males; mean age, 63.6 years) were included in the systematic evaluation. The results reported that there was no significant difference in OS (hazard ratio [HR] = 0.97 [P = 0.85]), PFS (HR = 0.95 [P = 0.14]), or ORR (odds ratio [OR] = 0.95 [P = 0.69]) between GEM + TA and GEM ± PLC. However, a marginal difference in 1-year survival rate (OR = 0.80 [P = 0.05]) between the 2 groups was observed. The grade 3/4 TRs of anemia, diarrhea, nausea, neutropenia, thrombocytopenia, and vomiting were not significantly different between the 2 groups. However, the prevalence of grade 3/4 rash was significantly greater in the GEM + TA group (OR = 8.31 [P < 0.01]).
  
  
  CONCLUSIONS
  Based on the results from this analysis, the addition of targeted agents to a regimen of gemcitabine treatment does not bring survival benefits except 1-year survival rate to patients with LA/MPC.
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People׳s Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People׳s Republic of China.
authors.forename: Zhenyan
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People׳s Republic of China.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: Experimental Center for Basic Medical Teaching, Capital Medical University, Beijing, People׳s Republic of China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People׳s Republic of China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People׳s Republic of China; Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, People׳s Republic of China; Beijing Digestive Diseases Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People׳s Republic of China. Electronic address: oncologychina@163.com.
authors.forename: Bangwei
authors.initials: B
authors.lastname: Cao
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D016206:Databases, Bibliographic; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: combination therapy; gemcitabine; pancreatic cancer; survival benefit; targeted agent