Top

Published in:

01-03-2020 | Pancreatic Cancer | Original Article

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

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

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2020

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.

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

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 CrossRef

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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

15.

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

16.

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

17.

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

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 CrossRefPubMed

19.

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

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 CrossRefPubMed

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 CrossRefPubMed

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):205–213CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRef

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 CrossRef

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 CrossRefPubMed

Title: Preoperative chemoradiotherapy using gemcitabine for pancreatic ductal adenocarcinoma in patients with impaired renal function
Authors: Yoshito Tomimaru
Hidetoshi Eguchi
Yoshifumi Iwagami
Hirofumi Akita
Takehiro Noda
Kunihito Gotoh
Shogo Kobayashi
Hiroaki Nagano
Masaki Mori
Yuichiro Doki
Publication date: 01-03-2020
Publisher: Springer Berlin Heidelberg
Keywords: Pancreatic Cancer
Pancreatic Cancer
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-04005-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2020

A Phase I dose-escalation, pharmacokinetics and food-effect study of oral donafenib in patients with advanced solid tumours

The influence of single-nucleotide polymorphisms on overall survival and toxicity in cabazitaxel-treated patients with metastatic castration-resistant prostate cancer

The use of Trichomonas vaginalis purine nucleoside phosphorylase to activate fludarabine in the treatment of solid tumors

Characterization of infections and hypogammaglobulinemia treated with the combination of pertuzumab and trastuzumab

Evaluation of gefitinib systemic exposure in EGFR-mutated non-small cell lung cancer patients with gefitinib-induced severe hepatotoxicity

Blood mRNA expression of REV3L and TYMS as potential predictive biomarkers from platinum-based chemotherapy plus pemetrexed in non-small cell lung cancer patients

Keynote webinar | Spotlight on antibody–drug conjugates in cancer