Skip to main content

Advertisement

SpringerLink
Log in

Early initiation of adjuvant chemotherapy improves survival of patients with pancreatic carcinoma after surgical resection

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Adjuvant chemotherapy is accepted as a standard treatment after surgical resection of pancreatic carcinoma; however, the optimal timing between surgery and initiation of adjuvant chemotherapy has not been reported. The aim of this study was to determine the optimal timing of adjuvant chemotherapy after surgical resection of pancreatic carcinoma.

Methods

Records of 104 patients who received adjuvant chemotherapy after curative surgical resection of pancreatic carcinoma were reviewed retrospectively. Patients were grouped according to whether they received initial adjuvant chemotherapy within 20 days after surgery (≦20 days, n = 57) or more than 20 days after surgery (>20 days, n = 47). Relationships between time to initiation of adjuvant chemotherapy, other clinicopathological factors, and survival were analyzed.

Results

The rate of postoperative complication was significantly lower than in the ≦20 days group compared with the >20 days group (P = 0.003); no significant difference in other clinicopathological factors was found. Multivariate analysis revealed that time to initiation of adjuvant chemotherapy was an independent prognostic factor of disease-free survival (P = 0.009) and overall survival (P = 0.037). The ≦20 days group had longer 5-year overall survival rates than did the >20 days group (52 vs. 26 %, P = 0.013) as well as longer 5-year disease-free survival rates (53 vs. 22 %, P = 0.007).

Conclusions

Adjuvant chemotherapy for patients with resected pancreatic carcinoma should be initiated as soon as possible after surgical resection. Prevention of postoperative complication is needed to enable early initiation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

    Article  PubMed  Google Scholar 

  2. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakashima A, Yuasa Y, Kondo N, Ohge H, Sueda T (2010) Number of metastatic lymph nodes, but not lymph node ratio, is an independent prognostic factor after resection of pancreatic carcinoma. J Am Coll Surg 211:196–204

    Article  PubMed  Google Scholar 

  3. Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, Hodgin MB, Sauter PK, Hruban RH, Riall TS, Schulick RD, Choti MA, Lillemoe KD, Yeo CJ (2006) 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg 10:1199–1211

    Article  PubMed  Google Scholar 

  4. Matsuno S, Egawa S, Fukuyama S, Motoi F, Sunamura M, Isaji S, Imaizumi T, Okada S, Kato H, Suda K, Nakao A, Hiraoka T, Hosotani R, Takeda K (2004) Pancreatic cancer registry in Japan: 20 years of experience. Pancreas 28:219–230

    Article  PubMed  Google Scholar 

  5. Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, Sauter PK, Coleman J, Hruban RH, Lillemoe KD (2000) Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 4:567–579

    Article  PubMed  CAS  Google Scholar 

  6. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Oláh A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler MW, European Study Group for Pancreatic Cancer (2010) Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine followed pancreatic cancer resection: a randomized controlled trial. JAMA 304:1073–1081

    Article  PubMed  CAS  Google Scholar 

  7. Van Laethem JL, Hammel P, Mornex F, Azria D, Van Tienhoven G, Vergauwe P, Peeters M, Polus M, Praet M, Mauer M, Collette L, Budach V, Lutz M, Van Cutsem E, Haustermans K (2010) Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study. J Clin Oncol 28:4450–4456

    Article  PubMed  Google Scholar 

  8. Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA (2008) Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299:1019–1026

    Article  PubMed  CAS  Google Scholar 

  9. Ueno H, Kosuge T, Matsuyama Y, Yamamoto J, Nakao A, Egawa S, Doi R, Monden M, Hatori T, Tanaka M, Shimada M, Kanemitsu K (2009) 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. Br J Cancer 101:908–915

    Article  PubMed  CAS  Google Scholar 

  10. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277

    Article  PubMed  CAS  Google Scholar 

  11. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW, European Study Group for Pancreatic Cancer (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210

    Article  PubMed  CAS  Google Scholar 

  12. Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T, Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract (2002) Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95:1685–1695

    Article  PubMed  Google Scholar 

  13. Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, Arnaud JP, Gonzalez DG, de Wit LT, Hennipman A, Wils J (1999) 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 230:776–784

    Article  PubMed  CAS  Google Scholar 

  14. Bakkevold KE, Arnesjo B, Dahl O, Kambestad B (1993) Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater–results of a controlled, prospective, randomised multicentre study. Eur J Cancer 29A:698–703

    Article  PubMed  CAS  Google Scholar 

  15. Gastrointestinal Tumour Study Group (1987) Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 59:2006–2010

    Article  Google Scholar 

  16. Lima IS, Yasui Y, Scarfe A, Winget M (2011) Association between receipt and timing of adjuvant chemotherapy and survival for patients with stage III colon cancer in Alberta, Canada. Cancer 117:3833–3840

    Article  PubMed  Google Scholar 

  17. Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM (2011) Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA 305:2335–2342

    Article  PubMed  CAS  Google Scholar 

  18. Des Guetz G, Nicolas P, Perret GY, Morere JF, Uzzan B (2010) Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer 46:1049–1055

    Article  PubMed  Google Scholar 

  19. Cheung WY, Neville BA, Earle CC (2009) Etiology of delays in the initiation of adjuvant chemotherapy and their impact on outcomes for Stage II and III rectal cancer. Dis Colon Rectum 52:1054–1063 (discussion 1064)

    Article  PubMed  Google Scholar 

  20. Hershman D, Hall MJ, Wang X, Jacobson JS, McBride R, Grann VR, Neugut AI (2006) Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer. Cancer 107:2581–2588

    Article  PubMed  Google Scholar 

  21. Alkis N, Durnali AG, Arslan UY, Kocer M, Onder FO, Tokluoglu S, Celenkoglu G, Muallaoglu S, Utkan G, Ulas A, Altundag K (2011) Optimal timing of adjuvant treatment in patients with early breast cancer. Med Oncol 28:1255–1259

    Article  PubMed  CAS  Google Scholar 

  22. Lohrisch C, Paltiel C, Gelmon K, Speers C, Taylor S, Barnett J, Olivotto IA (2006) Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol 24:4888–4894

    Article  PubMed  Google Scholar 

  23. Colleoni M, Bonetti M, Coates AS, Castiglione-Gertsch M, Gelber RD, Price K, Rudenstam CM, Lindtner J, Collins J, Thürlimann B, Holmberg S, Veronesi A, Marini G, Goldhirsch A (2000) Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. The International Breast Cancer Study Group. J Clin Oncol 18:584–590

    PubMed  CAS  Google Scholar 

  24. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakagawa N, Ohge H, Sueda T (2008) Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma. Am J Surg 195:757–762

    Article  PubMed  CAS  Google Scholar 

  25. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Ohge H, Sueda T (2009) Impact of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for adenocarcinoma of the body or tail of the pancreas. J Gastrointest Surg 13:85–92

    Article  PubMed  Google Scholar 

  26. Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Nakagawa N, Sueda T (2012) Long-term results of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic carcinoma. J Surg Oncol 106:174–180

    Article  PubMed  CAS  Google Scholar 

  27. Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, Ohge H, Sueda T (2007) Prognostic significance of lymph node metastasis and surgical margin status for distal cholangiocarcinoma. J Surg Oncol 95:207–212

    Article  PubMed  Google Scholar 

  28. Sudo T, Murakami Y, Uemura K, Hayashidani Y, Hashimoto Y, Ohge H, Shimamoto F, Sueda T (2008) Prognostic impact of perineural invasion following pancreatoduodenectomy with lymphadenectomy for ampullary carcinoma. Dig Dis Sci 53:2281–2286

    Article  PubMed  Google Scholar 

  29. Murakami Y, Uemura K, Ohge H, Hayashidani Y, Sudo T, Sueda T (2006) Intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms of the pancreas differentiated by ovarian-type stroma. Surgery 140:443–453

    Article  Google Scholar 

  30. Murakami Y, Uemura K, Sudo T, Hashimoto Y, Yuasa Y, Sueda T (2010) Prognostic impact of para-aortic lymph node metastasis in pancreatic carcinoma. World J Surg 34:1900–1907

    Article  PubMed  Google Scholar 

  31. Sobin LH, Gospodarowicz MK, Wittekind C (eds) (2010) International Union Against Cancer (UICC): TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, New York

    Google Scholar 

  32. Kondo N, Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, Nakashima A, Sakabe R, Shigemoto N, Kato Y, Ohge H, Sueda T (2010) Prognostic impact of perioperative serum CA 19–9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol 17:2321–2329

    Article  PubMed  Google Scholar 

  33. Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4–6

    Article  PubMed  CAS  Google Scholar 

  34. Eggermont AM, Steller EP, Sugarbaker PH (1987) Laparotomy enhances intraperitoneal tumor growth and abrogates the antitumor effects of interleukin-2 and lymphokine-activated killer cells. Surgery 102:71–78

    PubMed  CAS  Google Scholar 

  35. Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, Nakagawa N, Ohge H, Sueda T (2008) No mortality after 150 consecutive pancreatoduodenctomies with duct-to-mucosa pancreaticogastrostomy. J Surg Oncol 97:205–209

    Article  PubMed  Google Scholar 

  36. Shirasaka T, Shimamoto Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, Fukushima M (1996) Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumour selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs 7:548–557

    Article  PubMed  CAS  Google Scholar 

  37. Ioka T, Ikeda S, Ohkawa H, Yanagimoto H, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Chen JS, Mizumoto K, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Cheng AL, Okusaka T (2011) Randomized phase III study of gemcitabine plus S-1 (GS) versus S-1 versus gemcitabine (GEM) in unresectable advanced pancreatic cancer (PC) in Japan and Taiwan: GEST study. J Clin Oncol 29 (suppl; abstr 4007)

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Yoshiaki Murakami, Kenichiro Uemura, Takeshi Sudo, Yasushi Hashimoto, Naru Kondo, Naoya Nakagawa, Hayato Sasaki & Taijiro Sueda

Authors
  1. Yoshiaki Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenichiro Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takeshi Sudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasushi Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naru Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naoya Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hayato Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Taijiro Sueda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshiaki Murakami.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murakami, Y., Uemura, K., Sudo, T. et al. Early initiation of adjuvant chemotherapy improves survival of patients with pancreatic carcinoma after surgical resection. Cancer Chemother Pharmacol 71, 419–429 (2013). https://doi.org/10.1007/s00280-012-2029-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-012-2029-1

Keywords

Search

Navigation