Skip to main content

Advertisement

SpringerLink
Log in

Preoperative chemoradiotherapy using gemcitabine for pancreatic ductal adenocarcinoma in patients with impaired renal function

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

Abstract

Purpose

Preoperative chemoradiotherapy (CRT) can be a promising treatment for pancreatic ductal adenocarcinoma (PDAC). However, its administration for patients with impaired renal function has not been well investigated, let alone its clinical effect. We previously reported preliminary feasibility of CRT in PDAC patients with renal impairment. Herein, we aimed to investigate the clinical effects of preoperative CRT including safety and long-term prognosis in more PDAC patients with renal impairment as an extension to our previous work.

Methods

This study enrolled twenty patients harboring resectable PDAC with creatinine clearance level less than 60 ml/min. Patients underwent preoperative CRT with gemcitabine, followed by surgery. The clinical effects of the therapy were evaluated in terms of safety and long-term prognosis.

Results

Preoperative CRT was completed in all 20 patients. Grade 4 leukopenia/neutropenia was identified as an observed toxicity in four cases (20.0%). Renal function was not worsened after CRT. After CRT, 17 cases were judged resectable and underwent laparotomy. Pancreatic resection was performed in 15 of the 17 patients; it was not performed in two patients because of peritoneal dissemination. The 1-/3-/5-year cumulative survival rate from the initiation of CRT for the 20 patients was 88.8%/45.5%/22.8%. In the 15 patients, renal function was not worsened after surgery.

Conclusion

Our findings suggest that the clinical effects of preoperative CRT would be favorable in PDAC patients with renal impairment.

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 RL, Miller KD, Jemal A (2019) Cancer statistics. CA Cancer J Clin 69(1):7–34. https://doi.org/10.3322/caac.21551

    Article  PubMed  Google Scholar 

  2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2012) Global cancer statistics. CA Cancer J Clin 65(2):87–108. https://doi.org/10.3322/caac.21262

    Article  Google Scholar 

  3. 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, Buchler MW (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350(12):1200–1210. https://doi.org/10.1056/NEJMoa032295

    Article  CAS  PubMed  Google Scholar 

  4. 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(3):267–277. https://doi.org/10.1001/jama.297.3.267

    Article  CAS  PubMed  Google Scholar 

  5. Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H (2013) Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 310(14):1473–1481. https://doi.org/10.1001/jama.2013.279201

    Article  CAS  PubMed  Google Scholar 

  6. Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y (2016) Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet 388(10041):248–257. https://doi.org/10.1016/S0140-6736(16)30583-9

    Article  CAS  PubMed  Google Scholar 

  7. Evans DB, Varadhachary GR, Crane CH, Sun CC, Lee JE, Pisters PW, Vauthey JN, Wang H, Cleary KR, Staerkel GA, Charnsangavej C, Lano EA, Ho L, Lenzi R, Abbruzzese JL, Wolff RA (2008) Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26(21):3496–3502. https://doi.org/10.1200/JCO.2007.15.8634

    Article  CAS  PubMed  Google Scholar 

  8. Jang JY, Han Y, Lee H, Kim SW, Kwon W, Lee KH, Oh DY, Chie EK, Lee JM, Heo JS, Park JO, Lim DH, Kim SH, Park SJ, Lee WJ, Koh YH, Park JS, Yoon DS, Lee IJ, Choi SH (2018) Oncological benefits of neoadjuvant chemoradiation with gemcitabine versus upfront surgery in patients with borderline resectable pancreatic cancer: a prospective, randomized, open-label, multicenter phase 2/3 trial. Ann Surg 268(2):215–222. https://doi.org/10.1097/SLA.0000000000002705

    Article  PubMed  Google Scholar 

  9. Ohigashi H, Ishikawa O, Eguchi H, Takahashi H, Gotoh K, Yamada T, Yano M, Nakaizumi A, Uehara H, Tomita Y, Nishiyama K (2009) Feasibility and efficacy of combination therapy with preoperative full-dose gemcitabine, concurrent three-dimensional conformal radiation, surgery, and postoperative liver perfusion chemotherapy for T3-pancreatic cancer. Ann Surg 250(1):88–95. https://doi.org/10.1097/SLA.0b013e3181ad65cc

    Article  PubMed  Google Scholar 

  10. Takahashi H, Ohigashi H, Gotoh K, Marubashi S, Yamada T, Murata M, Ioka T, Uehara H, Yano M, Ishikawa O (2013) Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg 258(6):1040–1050. https://doi.org/10.1097/SLA.0b013e31829b3ce4

    Article  PubMed  Google Scholar 

  11. Eguchi H, Nagano H, Tanemura M, Takeda Y, Marubashi S, Kobayashi S, Kawamoto K, Wada H, Hama N, Akita H, Mori M, Doki Y (2013) Preoperative chemoradiotherapy, surgery and adjuvant therapy for resectable pancreatic cancer. Hepatogastroenterology 60(124):904–911. https://doi.org/10.5754/hge12974

    Article  CAS  PubMed  Google Scholar 

  12. Eguchi H, Takeda Y, Takahashi H, Nakahira S, Kashiwazaki M, Shimizu J, Sakai D, Isohashi F, Nagano H, Mori M, Doki Y (2019) A prospective, open-label, multicenter phase 2 trial of neoadjuvant therapy using full-dose gemcitabine and S-1 concurrent with radiation for resectable pancreatic ductal adenocarcinoma. Ann Surg Oncol 26(13):4498–4505. https://doi.org/10.1245/s10434-019-07735-8

    Article  PubMed  Google Scholar 

  13. Tomimaru Y, Eguchi H, Satoh T, Tomokuni A, Asaoka T, Wada H, Marubashi S, Ogawa K, Takehara T, Mori M, Doki Y, Nagano H (2015) Feasibility of pre-operative chemoradiotherapy with gemcitabine to treat pancreatic cancer in patients with impaired renal function. Jpn J Clin Oncol 45(4):343–348. https://doi.org/10.1093/jjco/hyu224

    Article  PubMed  Google Scholar 

  14. National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(2 Suppl 1):S1–S266

    Google Scholar 

  15. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41

    Article  CAS  PubMed  Google Scholar 

  16. Society JP (2017) Classification of pancreatic carcinoma, 4th edn. Kanehara and Co. Ltd, Tokyo

    Google Scholar 

  17. James D, Brierley MKG, Wittekind C (2017) TNM classification of malignant tumours, 8th edn. Splinger-Verlag, New York

    Google Scholar 

  18. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53(6):982–992. https://doi.org/10.1053/j.ajkd.2008.12.034

    Article  CAS  PubMed  Google Scholar 

  19. Nephrology TJSo (2018) Evidence-based clinical practice guideline for CKD 2018. Tokyo Igakusha Ltd, Tokyo

    Google Scholar 

  20. Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, Allen P, Andersson R, Asbun HJ, Besselink MG, Conlon K, Del Chiaro M, Falconi M, Fernandez-Cruz L, Fernandez-Del Castillo C, Fingerhut A, Friess H, Gouma DJ, Hackert T, Izbicki J, Lillemoe KD, Neoptolemos JP, Olah A, Schulick R, Shrikhande SV, Takada T, Takaori K, Traverso W, Vollmer CR, Wolfgang CL, Yeo CJ, Salvia R, Buchler M (2017) The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery 161(3):584–591. https://doi.org/10.1016/j.surg.2016.11.014

    Article  PubMed  Google Scholar 

  21. Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, Neoptolemos JP, Padbury RT, Sarr MG, Traverso LW, Yeo CJ, Buchler MW (2007) Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 142(5):761–768. https://doi.org/10.1016/j.surg.2007.05.005

    Article  PubMed  Google Scholar 

  22. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213

    Article  PubMed  PubMed Central  Google Scholar 

  23. Masumori N, Kunishima Y, Hirobe M, Takeuchi M, Takayanagi A, Tsukamoto T, Itoh T (2008) Measurement of plasma concentration of gemcitabine and its metabolite dFdU in hemodialysis patients with advanced urothelial cancer. Jpn J Clin Oncol 38(3):182–185. https://doi.org/10.1093/jjco/hym171

    Article  PubMed  Google Scholar 

  24. Janus N, Thariat J, Boulanger H, Deray G, Launay-Vacher V (2010) Proposal for dosage adjustment and timing of chemotherapy in hemodialyzed patients. Ann Oncol 21(7):1395–1403. https://doi.org/10.1093/annonc/mdp598

    Article  CAS  PubMed  Google Scholar 

  25. Muller S, Schutt P, Bojko P, Nowrousian MR, Hense J, Seeber S, Moritz T (2005) Hemolytic uremic syndrome following prolonged gemcitabine therapy: report of four cases from a single institution. Ann Hematol 84(2):110–114. https://doi.org/10.1007/s00277-004-0938-8

    Article  CAS  PubMed  Google Scholar 

  26. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703. https://doi.org/10.1056/NEJMoa1304369

    Article  CAS  Google Scholar 

  27. Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M (2011) Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol 29(34):4548–4554. https://doi.org/10.1200/JCO.2011.36.5742

    Article  CAS  Google Scholar 

  28. Shabason JE, Chen J, Apisarnthanarax S, Damjanov N, Giantonio B, Loaiza-Bonilla A, O'Dwyer PJ, O'Hara M, Reiss KA, Teitelbaum U, Wissel P, Drebin JA, Vollmer C, Kochman M, Mick R, Vergara N, Jhala N, Doucette A, Lukens JN, Plastaras JP, Metz JM, Ben-Josef E (2018) A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. Cancer Chemother Pharmacol 81(3):609–614. https://doi.org/10.1007/s00280-018-3519-6

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita, Osaka, 565-0871, Japan

    Yoshito Tomimaru, Hidetoshi Eguchi, Yoshifumi Iwagami, Hirofumi Akita, Takehiro Noda, Kunihito Gotoh, Shogo Kobayashi, Hiroaki Nagano, Masaki Mori & Yuichiro Doki

  2. Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan

    Hiroaki Nagano

  3. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masaki Mori

Authors
  1. Yoshito Tomimaru
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hidetoshi Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshifumi Iwagami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hirofumi Akita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takehiro Noda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kunihito Gotoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shogo Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiroaki Nagano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masaki Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yuichiro Doki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hidetoshi Eguchi.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tomimaru, Y., Eguchi, H., Iwagami, Y. et al. Preoperative chemoradiotherapy using gemcitabine for pancreatic ductal adenocarcinoma in patients with impaired renal function. Cancer Chemother Pharmacol 85, 537–545 (2020). https://doi.org/10.1007/s00280-019-04005-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-019-04005-y

Keywords

Search

Navigation