Objective: This study aimed at assessing the efficacy and safety of oxaliplatin plus oral capecitabine (XELOX regimen) as first-line chemotherapy in elderly patients with advanced gastric cancer (AGC). Patients and Methods: Forty-six eligible patients aged ≧70 years with previously untreated AGC received oxaliplatin 130 mg/m2 intravenously over a 2-hour period on day 1 plus oral capecitabine 850 mg/m2 twice daily on days 1–14, every 3 weeks. Results: All patients were evaluable for toxicity and 45 patients for efficacy. A median of 6 cycles (range 1–8) was administered. The overall response rate was 48.9% (95% CI 34–64) with 1 complete response, 21 partial responses, 15 stable diseases and 8 progressions. Median time to progression was 6.0 months (95% CI 3.9–8.1), and the median overall survival was 10.0 months (95% CI 8.6–11.4). Toxicity was fairly mild. Grade 3 toxicities included neutropenia (6.5%), thrombocytopenia (2.2%), nausea (2.2%), vomiting (4.3%), diarrhea (4.3%) as well as peripheral neuropathy (2.2%); grade 4 toxicities occurred in none of the patients. Conclusion: The XELOX regimen with capecitabine at a lower dose of 850 mg/m2 is active, fairly tolerable and conveniently delivered as first-line chemotherapy for elderly AGC patients.

1.
Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics. CA Cancer J Clin 2005;55:74–108.
2.
Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS: Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999;341:2061–2067.
3.
Talarico L, Chen G, Pazdur R: Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 2004;22:4626–4631.
4.
Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE: Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 2006;24:2903–2909.
5.
Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Rindlay M, Hill A, Oates J, Nicolson M, Hickish T, O’Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M: Randomized trial comparing epirubicin, cisplatin, and 5-fluorouracil versus 5-fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 1997;15:261–267.
6.
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR: Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358:36–46.
7.
Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA: Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 2006;24:4991–4997.
8.
Graziano F, Santini D, Testa E, Catalano V, Beretta GD, Mosconi S, Tonini G, Lai V, Labianca R, Cascinu S: A phase II study of weekly cisplatin, 6S-stereoisomer leucovorin and fluorouracil as first-line chemotherapy for elderly patients with advanced gastric cancer. Br J Cancer 2003;8:1428–1432.
9.
Louvet C, Andre T, Tigaud JM, Gamelin E, Douillard JY, Brunet R, Francois E, Jacob JH, Levior D, Taamma A, Rougier P, Cvitkovic E, De Gramont A: Phase II study of oxaliplatin, fluorouracil and folinic acid in locally advanced or metastatic gastric cancer patients. J Clin Oncol 2002;20:4543–4548.
10.
Al-Batran SE, Atmaca A, Hegewisch-Becker S, Jaeger D, Hahnfeld S, Rummel MJ, Seipelt G, Rost A, Orth J, Knuth A, Jaeger E: Phase II trial of biweekly infusional fluorouracil, folinic acid, and oxaliplatin in patients with advanced gastric cancer. J Clin Oncol 2004;22:658–663.
11.
Lim JY, Cho JY, Oh KJ, Choi SH, Lee SI, Jeung HC: Oxaliplatin combined with continuous infusion of 5-fluorouracil as first-line chemotherapy in patients with metastatic or recurrent gastric adenocarcinoma. Chemotherapy 2009;55:200–206.
12.
Santini D, Graziano F, Catalano V, Seri MD, Testa E, Baldelli AM, Giordani P, Cesa AL, Spalletta B, Vincenzi B, Russo A, Caraglia M, Virzi V, Cascinu S, Tonini G: Weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) as first-line chemotherapy for elderly patients with advanced gastric cancer: results of a phase II trial. BMC Cancer 2006;6:125.
13.
Nardi M, Azzarello D, Maisano R, Medico PD, Giannicola R, Raffaele M, Zavettieri M, Costarella S, Falzea A: FOLFOX-4 regimen as fist-line chemotherapy in elderly patients with advanced gastric cancer: a safety study. J Chemother 2007;19:85–89.
14.
Liu ZF, Guo QS, Zhang XQ, Yang XG, Guan F, Fu Z, Wang MY: Biweekly oxaliplatin in combination with continuous infusional 5-fluorouracil and leucovorin (modified FOLFOX-4 regimen) as first-line chemotherapy for elderly patients with advanced gastric cancer. Am J Clin Oncol 2008;31:259–263.
15.
Zhao JG, Qiu F, Xiong JP, Zhang L, Xiang XJ, Yu F, Yan J, Zhan ZY, Feng M: A phase II study of modified FOLFOX as first-line chemotherapy in elderly patients with advanced gastric cancer. Anticancer Drugs 2009;20:281–286.
16.
Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E: Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol 2008;26:1435–1442.
17.
Montagnani F, Turrisi G, Marnozzi C, Aliberti C, Fiorentini G: Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis. Gastric Cancer 2011;14:50–55.
18.
Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R: Comparison of oral capecitabine vs intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 2001;19:2282–2292.
19.
Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P: Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 2001;19:4097–4106.
20.
Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L: Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 2008;26:2006–2012.
21.
Hong YS, Song SY, Cho JY, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY: A phase II trial of capecitabine in chemotherapy naive patients with advanced and/or metastatic gastric cancer. Ann Oncol 2004;15:1344–1347.
22.
Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI: Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 2009;20:666–673.
23.
Okines AF, Normanl AR, McCloud P, Kang YK, Cunningham D: Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol 2009;20:1529–1534.
24.
Jatoi A, Murphy BR, Foster NR, Nikcevich DA, Alberts SR, Knost JA, Fitch TR, Rowland KM Jr: Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group. Ann Oncol 2006;17:29–34.
25.
Park YH, Kim BS, Ryoo BY, Yang SH: A phase II study of capecitabine plus 3-weekly oxaliplatin as first-line therapy for patients with advanced gastric cancer. Br J Cancer 2006;94:959–963.
26.
Park YH, Lee JL, Ryoo BY, Ryu MH, Yang SH, Kim BS, Shin DB, Chang HM, Kim TW, Yuh YJ, Kang YK: Capecitabine in combination with oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer. Cancer Chemother Pharmacol 2008;61:623–629.
27.
Liu CY, Sun Q, Hang XS, Zhong BL, Wang DY: Multicenter phase II study of capecitabine plus oxaliplatin as a first-line therapy in Chinese patients with advanced gastric cancer. Anticancer Drugs 2008;19:825–831.
28.
Luo HY, Xu RH, Wang F, Qiu MZ, Li YH, Li FH, Zhou ZW, Chen XQ: Phase II trial of XELOX as first-line treatment for patients with advanced gastric cancer. Chemotherapy 2010;56:94–100.
29.
Blum JL, Jones SE, Buzdar AU, Lorusso PM, Kuter I, Vogel C, Osterwalder B, Burger HU, Brown CS, Griffin T: Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 1999;17:485–493.
30.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205–216.
31.
Simon R: Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1–10.
32.
Seol YM, Song MK, Choi YJ, Kim GH, Shin HJ, Song GA, Chung JS, Cho GJ: Oral fluoropyrimidines (capecitabine or S-1) and cisplatin as first line treatment in elderly patients with advanced gastric cancer: a retrospective study. Jpn J Clin Oncol 2009;39:43–48.
33.
Shields AF, Zalupski MM, Marshall JL, Meropol NJ: Treatment of advanced colorectal carcinoma with oxaliplatin and capecitabine: a phase II trial. Cancer 2004;100:531–537.
34.
Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, Wong L, Fehrenbacher L, Abubakr Y, Saif MW, Schwartzberg L, Hedrick E: Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 2008;26:3523–3529.
35.
Dong NN, Jiang WR, Li HQ, Liu ZF, Xu XQ, Wang MY: Triweekly oxaliplatin plus oral capecitabine as first-line chemotherapy in elderly patients with advanced gastric cancer. Am J Clin Oncol 2009;32:559–563.
36.
Haller DG, Cassidy J, Clarke SJ, Cunningham D, et al: Potential regional differences for the tolerability profiles of fluoropyrimidines. J Clin Oncol 2008;26:2118–2123.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.