Influencing on Survival of Postoperative Adjuvant Chemotherapy for Pancreatic Cancer Patients after Operation: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 WANGHai-jing ¹ , ZHANGLi-zhen ¹ , TIANJi-hong ¹ , BILiang-wen ¹ , HUANGPu-wen ²

1. Department of Radiotherapy, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China;
2. Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China;

Corresponding author：

Keywords：

Pancreatic cancer; Adjuvant chemotherapy; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20140238

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Objective To systematically review the influence of postoperative adjuvant chemotherapy for pancreatic cancer on survival. Methods We comprehensively searched databases including The Cochrane Library (Issue 11, 2013), PubMed, EMbase, CBM, CNKI, VIP and WanFang Data from inception to December 2013 to collect randomized controlled trials (RCTs) about the influencing on survival of postoperative adjuvant chemotherapy for pancreatic cancer patients after operation. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Then meta-analysis was conducted using RevMan 5.2 software. Results A total of 7 RCTs involving 1 079 patients were included (544 cases and 535 controls). The results of meta-analysis showed that, compared with single radical correction, the patients with adjuvant chemotherapy were better in prolonging total survival time (WMD=5.45, 95%CI 2.52 to 8.39, P=0.000 3), and increasing 2-year (RR=1.17, 95%CI 1.01 to 1.35, P=0.03) as well as 5-year survival rates (RR=1.80, 95%CI 1.24 to 2.62, P=0.002) with significant differences. But for 1-year survival rates, no significant difference was found between the two groups (RR=1.02, 95%CI 0.94 to 1.11, P=0.65). Conclusion Current evidence shows that postoperative adjuvant chemotherapy should be applied after resection of pancreatic cancer.

Citation： WANGHai-jing, ZHANGLi-zhen, TIANJi-hong, BILiang-wen, HUANGPu-wen. Influencing on Survival of Postoperative Adjuvant Chemotherapy for Pancreatic Cancer Patients after Operation: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2014, 14(12): 1491-1496. doi: 10.7507/1672-2531.20140238 Copy

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2.	Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabin vs. observation in patients undergoing curative-intent resection of pancreatic cancer:A randomized controlled trial. JAMA, 2007, 297(3):267-277.
3.	Ueno H, Kosuge T, Matsuyama Y, et al. A randomized phase Ⅲ trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer:Japanese study group of adjuvant therapy for pancreatic cancer. Brit J Cancer, 2009, 101(6):908-915.
4.	Kosuge T, Kiuchi T, Mukai K, et al. A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer. Jpn J Clin Oncol, 2006, 36(3):159-165.
5.	Bakkevold KE, Arnesjo B, Dahl O, et al. Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of vater-results of a controlled, prospective, randomized multicenter study. Eur J Cancer, 1993, 29(5):698-703.
6.	Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer:a randomized controlled trial. Lancet, 2001, 358(9293):1576-1585.
7.	Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoraidotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med, 2004, 350(12):1200-1210.
8.	Neoptolemos JP, Stocken DD, Smith TC, et al. Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer:composite data from the ESPAC-1 and-3(vl) trials. Brit J Cancer, 2009, 100(2):246-250.
9.	Pedrazzoli S, DiCarlo V, Dionigi R, et al. Standard versus extended lymphadenectomy associated with pancreaticoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas:a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg, 2009, 228(4):508-517.
10.	Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcima, part 2:randomized control trial evaluating survival, morbidity, and mortality. Ann Surg, 2002, 236(3):355-368.
11.	Farnell MB, Pearson RK, Sarr MG, et al. A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery, 2005, 138(4):618-628.
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13.	Burris HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced cancer:a randomized trial. J Clin Oncol, 1997, 15(6):2403-2413.
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16.	Warshaw AL, Fernandez-del CC. Pancreatic carcinoma. N Engl J Med, 1992, 326(7):455-465.
17.	Neoptolemos JP, Buchler M, Stocken DD, et al. ESPAC-3(v2):A multicenter, international, open-label, randomized, controlled phase Ⅲ trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma. J Clin Oncol, 2009, 27(28s):LBA4505.
18.	Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma?A phase Ⅲ multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer, 2002, 95(8):1685-1695.
19.	Klinkenbijl J, Jeekel J, Sahmoud T, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region:phase Ⅲ trial of the EORTC Gastrointestinal Tract Cancer Cooperative Group. Ann Surg, 1999, 230(6):776-782.
20.	Regine WF, Winter KW, Abrams R, et al. RTOG 9704 a phase Ⅲ study of adjuvant pre and post chemoradiation (CRT) 5FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma. J Clin Oncol, 2006, 24(18S):LBA4007.
21.	Kalser MH, Ellenberg SS. Pancreatic cancer.Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg, 2006, 120(8):899-903.
22.	Abou-Alfa GK, Letourneau R, Harker G, et al. Randomised phase Ⅲ study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol, 2006, 24(27):4441-4447.
23.	Berlin JD, Catalano P, Thomas JP, et al. Phase Ⅲ study of gemcitabine in combination with fluorouracil vs gemcitabine alone in patients with advanced pancreatic carcinoma:Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol, 2002, 20(15):3270-3275.
24.	Bria E, Milella M, Gelibter A, et al. Gemcitabine-based combination for inoperable pancreatic cancer:have we made real progres? A meta-analysis of 20 phase 3 trials. Cancer, 2007, 110(3):525-533.
25.	Golucci G, Giuliani F, Gebbia V, et al. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma.A prospective, randomised phase Ⅲ study of the Gruppo Oncologico dell'Italia Meridionale. Cancer, 2002, 94(4):902-910.
26.	Sultana A, Smith CT, Cunningham D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer:results of secondary end points analyses. Brit J Cancer, 2008, 99(1):6-13.
27.	Burris HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer:a randomized trial. J Clin Oncol, 1997, 15(6):2403-2413.
28.	Suzuki S, Morishita K, Kaji S, et al. Effectiveness of adjuvant chemotherapy using gemcitabine for resected pancreatic cancer. Gan To Kagaku Ryoho, 2011, 38(1):65-68.
29.	Murakami Y, Uemura K, Sudo T, et al. Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. The American Journal of Surgery, 2008, 195(6):757-762.

1. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin, 2012, 62(1):10-29.
2. Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabin vs. observation in patients undergoing curative-intent resection of pancreatic cancer:A randomized controlled trial. JAMA, 2007, 297(3):267-277.
3. Ueno H, Kosuge T, Matsuyama Y, et al. A randomized phase Ⅲ trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer:Japanese study group of adjuvant therapy for pancreatic cancer. Brit J Cancer, 2009, 101(6):908-915.
4. Kosuge T, Kiuchi T, Mukai K, et al. A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer. Jpn J Clin Oncol, 2006, 36(3):159-165.
5. Bakkevold KE, Arnesjo B, Dahl O, et al. Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of vater-results of a controlled, prospective, randomized multicenter study. Eur J Cancer, 1993, 29(5):698-703.
6. Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer:a randomized controlled trial. Lancet, 2001, 358(9293):1576-1585.
7. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoraidotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med, 2004, 350(12):1200-1210.
8. Neoptolemos JP, Stocken DD, Smith TC, et al. Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer:composite data from the ESPAC-1 and-3(vl) trials. Brit J Cancer, 2009, 100(2):246-250.
9. Pedrazzoli S, DiCarlo V, Dionigi R, et al. Standard versus extended lymphadenectomy associated with pancreaticoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas:a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg, 2009, 228(4):508-517.
10. Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcima, part 2:randomized control trial evaluating survival, morbidity, and mortality. Ann Surg, 2002, 236(3):355-368.
11. Farnell MB, Pearson RK, Sarr MG, et al. A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery, 2005, 138(4):618-628.
12. Stocken DD, Buchler MW, Derveins C, et al. Meta-analysis of randomized adjuvant therapy trials for pancreatic cancer. Brit J Cancer, 2005, 92(8):1372-1381.
13. Burris HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced cancer:a randomized trial. J Clin Oncol, 1997, 15(6):2403-2413.
14. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011]. The Cochrane Collaboration, 2011.
15. Neuhaus P, Riess H, Post S, et al. CONKO-001:Final results of the randomized, prospective, multicenter phase Ⅲ trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer (PC). J Clin Oncol, 2008, 26(15s):LBA4504.
16. Warshaw AL, Fernandez-del CC. Pancreatic carcinoma. N Engl J Med, 1992, 326(7):455-465.
17. Neoptolemos JP, Buchler M, Stocken DD, et al. ESPAC-3(v2):A multicenter, international, open-label, randomized, controlled phase Ⅲ trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma. J Clin Oncol, 2009, 27(28s):LBA4505.
18. Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma?A phase Ⅲ multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer, 2002, 95(8):1685-1695.
19. Klinkenbijl J, Jeekel J, Sahmoud T, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region:phase Ⅲ trial of the EORTC Gastrointestinal Tract Cancer Cooperative Group. Ann Surg, 1999, 230(6):776-782.
20. Regine WF, Winter KW, Abrams R, et al. RTOG 9704 a phase Ⅲ study of adjuvant pre and post chemoradiation (CRT) 5FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma. J Clin Oncol, 2006, 24(18S):LBA4007.
21. Kalser MH, Ellenberg SS. Pancreatic cancer.Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg, 2006, 120(8):899-903.
22. Abou-Alfa GK, Letourneau R, Harker G, et al. Randomised phase Ⅲ study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol, 2006, 24(27):4441-4447.
23. Berlin JD, Catalano P, Thomas JP, et al. Phase Ⅲ study of gemcitabine in combination with fluorouracil vs gemcitabine alone in patients with advanced pancreatic carcinoma:Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol, 2002, 20(15):3270-3275.
24. Bria E, Milella M, Gelibter A, et al. Gemcitabine-based combination for inoperable pancreatic cancer:have we made real progres? A meta-analysis of 20 phase 3 trials. Cancer, 2007, 110(3):525-533.
25. Golucci G, Giuliani F, Gebbia V, et al. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma.A prospective, randomised phase Ⅲ study of the Gruppo Oncologico dell'Italia Meridionale. Cancer, 2002, 94(4):902-910.
26. Sultana A, Smith CT, Cunningham D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer:results of secondary end points analyses. Brit J Cancer, 2008, 99(1):6-13.
27. Burris HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer:a randomized trial. J Clin Oncol, 1997, 15(6):2403-2413.
28. Suzuki S, Morishita K, Kaji S, et al. Effectiveness of adjuvant chemotherapy using gemcitabine for resected pancreatic cancer. Gan To Kagaku Ryoho, 2011, 38(1):65-68.
29. Murakami Y, Uemura K, Sudo T, et al. Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. The American Journal of Surgery, 2008, 195(6):757-762.

Chinese Journal of Evidence-Based Medicine

Influencing on Survival of Postoperative Adjuvant Chemotherapy for Pancreatic Cancer Patients after Operation: A Meta-Analysis

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