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Published in: Medical Oncology 5/2012

01-12-2012 | Original Paper

Long-term outcome of continuous 5-fluorouracil/cisplatin-based chemotherapy followed by chemoradiation in patients with resected gastric cancer

Authors: Amir Sonnenblick, Yakir Rottenberg, Luna Kadouri, Marc Wygoda, Avraham Rivkind, Gilad W. Vainer, Tamar Peretz, Ayala Hubert

Published in: Medical Oncology | Issue 5/2012

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Abstract

Despite substantial developments in gastric cancer treatment, the majority of patients relapse after definitive surgery. We have previously described well-tolerated adjuvant regimen that includes a combination of bolus 5-fluorouracil, continuous 5-fluorouracil, and cisplatin followed by chemoradiation after 3 months of chemotherapy. The aim of this study was to evaluate long-term outcomes of patients treated with this regimen and to determine whether expressions of the excision repair cross-complementing (ERCC1) and thymidylate synthase (TS) predict clinical outcome in those patients. The study population consisted of 36 advanced gastric cancer patients. Patients were treated with six cycles of continuous 5-fluorouracil (600 mg/m2) for 24 h, push 5-fluorouracil (400 mg/m2), and leucoverin (LCV) (200 mg/m2) on day 1–2 every 2 weeks, cisplatin (60 mg/m2) on day 1 every 4 weeks followed by combined modality therapy using 45 Gy at 1.8 Gy per day concomitant with weekly bolus 5-fluorouracil (600 mg/m2) and LCV (50 mg). After median follow-up of 48.9 months, the median disease-free survival was 45 months and the overall survival was 66.4 months. Sixteen patients (44 %) were alive and disease-free. There was no significant correlation between ERCC1 expression and TS expression pattern and time to relapse (P = 0.302 and P = 0.707, respectively). In conclusion, long-term follow-up demonstrates that postoperative chemoradiation with combination of bolus 5-fluorouracil, continuous 5-fluorouracil, and cisplatin is a feasible approach.
Literature
1.
go back to reference Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin. 1999;49(1):33–64, 1. Parkin DM, Pisani P, Ferlay J. Global cancer statistics. CA Cancer J Clin. 1999;49(1):33–64, 1.
2.
go back to reference Lim L, Michael M, Mann GB, Leong T. Adjuvant therapy in gastric cancer. J Clin Oncol. 2005;23(25):6220–32.PubMedCrossRef Lim L, Michael M, Mann GB, Leong T. Adjuvant therapy in gastric cancer. J Clin Oncol. 2005;23(25):6220–32.PubMedCrossRef
3.
go back to reference Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30.PubMedCrossRef Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30.PubMedCrossRef
4.
go back to reference Yakir R, Luna K, Marc W, Tamar S, Avraham R, Ayala H. The toxicity and outcomes of continuous 5-fluorouracil/cisplatin-based chemotherapy followed by chemoradiation in patients with resected high-risk gastric cancer: results of a single institute. Ann Acad Med Singap. 2008;37(3):200–4.PubMed Yakir R, Luna K, Marc W, Tamar S, Avraham R, Ayala H. The toxicity and outcomes of continuous 5-fluorouracil/cisplatin-based chemotherapy followed by chemoradiation in patients with resected high-risk gastric cancer: results of a single institute. Ann Acad Med Singap. 2008;37(3):200–4.PubMed
5.
go back to reference Kohne CH, Wils J, Lorenz M, Schoffski P, Voigtmann R, Bokemeyer C, et al. Randomized phase III study of high-dose fluorouracil given as a weekly 24-hour infusion with or without leucovorin versus bolus fluorouracil plus leucovorin in advanced colorectal cancer: European organization of research and treatment of cancer gastrointestinal group study 40952. J Clin Oncol. 2003;21(20):3721–8.PubMedCrossRef Kohne CH, Wils J, Lorenz M, Schoffski P, Voigtmann R, Bokemeyer C, et al. Randomized phase III study of high-dose fluorouracil given as a weekly 24-hour infusion with or without leucovorin versus bolus fluorouracil plus leucovorin in advanced colorectal cancer: European organization of research and treatment of cancer gastrointestinal group study 40952. J Clin Oncol. 2003;21(20):3721–8.PubMedCrossRef
6.
go back to reference Park SR, Chun JH, Kim YW, Lee JH, Choi IJ, Kim CG, et al. Phase II study of low-dose docetaxel/fluorouracil/cisplatin in metastatic gastric carcinoma. Am J Clin Oncol. 2005;28(5):433–8.PubMedCrossRef Park SR, Chun JH, Kim YW, Lee JH, Choi IJ, Kim CG, et al. Phase II study of low-dose docetaxel/fluorouracil/cisplatin in metastatic gastric carcinoma. Am J Clin Oncol. 2005;28(5):433–8.PubMedCrossRef
7.
go back to reference Johnson NP, Hoeschele JD, Rahn RO. Kinetic analysis of the in vitro binding of radioactive cis- and trans-dichlorodiammineplatinum(II) to DNA. Chem Biol Interact. 1980;30(2):151–69.PubMedCrossRef Johnson NP, Hoeschele JD, Rahn RO. Kinetic analysis of the in vitro binding of radioactive cis- and trans-dichlorodiammineplatinum(II) to DNA. Chem Biol Interact. 1980;30(2):151–69.PubMedCrossRef
8.
go back to reference Kwon HC, Roh MS, Oh SY, Kim SH, Kim MC, Kim JS, et al. Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer. Ann Oncol. 2007;18(3):504–9.PubMedCrossRef Kwon HC, Roh MS, Oh SY, Kim SH, Kim MC, Kim JS, et al. Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer. Ann Oncol. 2007;18(3):504–9.PubMedCrossRef
9.
go back to reference Yeh KH, Shun CT, Chen CL, Lin JT, Lee WJ, Lee PH, et al. High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy. Cancer. 1998;82(9):1626–31.PubMedCrossRef Yeh KH, Shun CT, Chen CL, Lin JT, Lee WJ, Lee PH, et al. High expression of thymidylate synthase is associated with the drug resistance of gastric carcinoma to high dose 5-fluorouracil-based systemic chemotherapy. Cancer. 1998;82(9):1626–31.PubMedCrossRef
10.
go back to reference Choi J, Lim H, Nam DK, Kim HS, Cho DY, Yi JW, et al. Expression of thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection. Br J Cancer. 2001;84(2):186–92.PubMedCrossRef Choi J, Lim H, Nam DK, Kim HS, Cho DY, Yi JW, et al. Expression of thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection. Br J Cancer. 2001;84(2):186–92.PubMedCrossRef
11.
go back to reference Lenz HJ, Leichman CG, Danenberg KD, Danenberg PV, Groshen S, Cohen H, et al. Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol. 1996;14(1):176–82.PubMed Lenz HJ, Leichman CG, Danenberg KD, Danenberg PV, Groshen S, Cohen H, et al. Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol. 1996;14(1):176–82.PubMed
12.
go back to reference Bouche O, Ychou M, Burtin P, Bedenne L, Ducreux M, Lebreton G, et al. Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Ann Oncol. 2005;16(9):1488–97.PubMedCrossRef Bouche O, Ychou M, Burtin P, Bedenne L, Ducreux M, Lebreton G, et al. Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Ann Oncol. 2005;16(9):1488–97.PubMedCrossRef
13.
go back to reference Bajetta E, Buzzoni R, Mariani L, Beretta E, Bozzetti F, Bordogna G, et al. Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian Trials in Medical Oncology (ITMO) Group. Ann Oncol. 2002;13(2):299–307.PubMedCrossRef Bajetta E, Buzzoni R, Mariani L, Beretta E, Bozzetti F, Bordogna G, et al. Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian Trials in Medical Oncology (ITMO) Group. Ann Oncol. 2002;13(2):299–307.PubMedCrossRef
14.
go back to reference Lord RV, Brabender J, Gandara D, Alberola V, Camps C, Domine M, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002;8(7):2286–91.PubMed Lord RV, Brabender J, Gandara D, Alberola V, Camps C, Domine M, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002;8(7):2286–91.PubMed
15.
go back to reference Shirota Y, Stoehlmacher J, Brabender J, Xiong YP, Uetake H, Danenberg KD, et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol. 2001;19(23):4298–304.PubMed Shirota Y, Stoehlmacher J, Brabender J, Xiong YP, Uetake H, Danenberg KD, et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol. 2001;19(23):4298–304.PubMed
16.
go back to reference Metzger R, Leichman CG, Danenberg KD, Danenberg PV, Lenz HJ, Hayashi K, et al. ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol. 1998;16(1):309–16.PubMed Metzger R, Leichman CG, Danenberg KD, Danenberg PV, Lenz HJ, Hayashi K, et al. ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol. 1998;16(1):309–16.PubMed
17.
go back to reference Johnston PG, Lenz HJ, Leichman CG, Danenberg KD, Allegra CJ, Danenberg PV, et al. Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res. 1995;55(7):1407–12.PubMed Johnston PG, Lenz HJ, Leichman CG, Danenberg KD, Allegra CJ, Danenberg PV, et al. Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res. 1995;55(7):1407–12.PubMed
Metadata
Title
Long-term outcome of continuous 5-fluorouracil/cisplatin-based chemotherapy followed by chemoradiation in patients with resected gastric cancer
Authors
Amir Sonnenblick
Yakir Rottenberg
Luna Kadouri
Marc Wygoda
Avraham Rivkind
Gilad W. Vainer
Tamar Peretz
Ayala Hubert
Publication date
01-12-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 5/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-012-0302-0

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