Elsevier

Surgery

Volume 150, Issue 3, September 2011, Pages 466-473
Surgery

Society of University Surgeons
Neoadjuvant therapy in pancreatic adenocarcinoma: A meta-analysis of phase II trials

https://doi.org/10.1016/j.surg.2011.07.006Get rights and content

Background

Neoadjuvant treatment has proven beneficial for many gastrointestinal (GI) malignancies, but no phase III trials have been completed examining this approach in pancreatic cancer. This meta-analysis examines the best available phase II trials using neoadjuvant treatment for resectable and borderline/unresectable pancreatic adenocarcinoma.

Methods

Phase II trials were identified using a MEDLINE search, and the Cochrane Central Register of Controlled Trials from 1960 to July 2010. Patients were divided into 2 groups: Patients with initially resectable tumors (group A), and patients with borderline/unresectable tumors (group B). Primary outcome measures were rate of resection and survival. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies.

Results

A total of 14 phase II clinical trials including 536 patients were analyzed. After treatment, resectability was 65.8% (95% CI, 55.4–75.6%) compared with 31.6% in group B (95% CI, 14.0–52.5%). A partial response was observed in patients with borderline/unresectable tumors; 31.8 (95% CI, 24.2–39.8%) in group B and 9.5% (95% CI, 2.9–19.4%) in group A (P = .003). Progressive disease was seen in 17.0% (95% CI, 11.9–22.7) of patients in group A versus 21.8% (95% CI, 10.1–36.5%) in group B (P = .006). Median survival in resected patients was 23 months for group A and 22 months for group B.

Conclusion

Neoadjuvant treatment seems to have some activity in patients with borderline/unresectable pancreatic adenocarcinoma. Nearly one third of tumors initially deemed marginal for operative intervention were able to be ultimately resected after treatment. Until more effective targeted chemotherapeutics are developed, the only group of patients with pancreatic cancer that may benefit from neoadjuvant treatment are those with locally advanced disease.

Section snippets

Study design and data collection

Studies considered for our meta-analysis included prospective phase II trials investigating the effects of neoadjuvant chemotherapy and/or neoadjuvant radiation on patients with locally advanced and unresectable pancreatic cancer. Retrospective studies, phase I trials, cohort studies, case series, and case reports were excluded.

Studies were identified using MEDLINE, and the Cochrane Central Register of Controlled Trials from 1960 to July 2010. The following key words and phrases were used to

Results

Out of 397 initially retrieved studies, 14 phase II trials from 1993 to 2010 were chosen to include in this meta-analysis (Supplemental Table). The 14 phase II trials included 536 patients. The University of Texas M.D. Anderson Cancer Center (Houston, TX) and the Fox Chase Cancer Center (Philadelphia, PA) each published 2 studies. All other studies were published by independent groups.

All 14 trials were prospective studies. Twelve (86%) were single-arm studies, and 2 trials randomized patients

Discussion

The aim of this meta-analysis and review of the literature was to investigate the potential role for neoadjuvant treatment in patients with pancreatic adenocarcinoma. Neoadjuvant therapy has been shown to have a substantial impact in several GI malignancies and has many theoretic advantages over adjuvant treatment in patients with pancreatic adenocarcinoma. Preoperative treatment has been proposed to have greater benefits on well-oxygenated, nondevascularized tissue, with improved delivery of

Conclusion

The data compiled from this meta-analysis highlight the importance of preoperative staging. Despite the limitations of this study, the data suggest that patients with borderline or unresectable disease may achieve the most benefit from neoadjuvant treatment. Like other GI malignancies, treating patients with borderline resectable pancreatic cancer before operative intervention may allow for resection in a substantial number of these patients, and provides a period of time to select those

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