Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies.
BACKGROUND
Long-term prognosis for localized pancreatic cancer remains poor. We sought to assess the benefit of neoadjuvant/preoperative chemotherapy with or without radiotherapy.


METHODS
Prospective studies where gemcitabine with or without radiotherapy was provided before surgery in patients with initially resectable or unresectable disease were reviewed by meta-analysis. Primary outcome was survival, and secondary outcomes were tumor response after therapy, toxicity, surgical exploration, and resection rates.


RESULTS
Twenty independent studies with 707 participants were included, 366 with resectable lesions and 341 with unresectable lesions. Seven studies were phase I/II trials, 10 phase II, and 3 prospective cohort studies. Estimated 1- and 2-year survival probabilities after resection were 91.7% (95% confidence interval [CI] 75-100) and 67.2% (95% CI 38-87) for initially resectable patients, and 86.3% (95% CI 78-100) and 54.2% (95% CI 25-100) for initially unresectable patients. The complete/partial response rate was 12% (95% CI 4-23) and 27% (95% CI 18-38) in resectable and unresectable lesions, respectively. The rate of treatment-related grade 3-4 toxicity was 31% (95% CI 21-42). Of resectable patients evaluable after restaging, 91% (95% CI 83-97) underwent surgery, and 82% (95% CI 65-95) of explored patients underwent resection. R0 resections amounted to 89% (95% CI 83-94). Of unresectable patients evaluable after restaging, 39% (95% CI 28-50) underwent surgery, and 68% (95% CI 53-82) of explored patients were resected, with 60% (95% CI 50-71) R0 resections.


CONCLUSIONS
Current analysis provides marginal support to the assumed benefits of neoadjuvant therapies for patients with resectable cancer, and indicates a potential advantage only for a minority of those with unresectable lesions.
Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo, Italy.
Angelo
A
Andriulli
Virginia
V
Festa
Edoardo
E
Botteri
Maria R
MR
Valvano
Maurizio
M
Koch
Claudio
C
Bassi
Patrick
P
Maisonneuve
Pierluigi Di
PD
Sebastiano
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011292:Premedication; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D000093542:Gemcitabine