A multicenter phase II study of biweekly capecitabine in combination with oxaliplatin as first-line chemotherapy in patients with locally advanced or metastatic gastric cancer

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• 作者：Yee Chao (1) (2)
  Jan-Sing Hsieh (3) (4)
  Hsien-Tang Yeh (5)
  Yu-Chieh Su (6)
  Cheng-Chung Wu (2) (7)
  Jen-Shi Chen (8)
  Cheng-Jeng Tai (10) (9)
  Li-Yuan Bai (11)
  Kun-Huei Yeh (12)
  Wu-Chou Su (13)
  Chung-Pin Li (14) (2)
  
• 关键词：Gastric cancer ; Phase II study ; Biweekly XELOX ; Capecitabine ; Oxaliplatin
• 刊名：Cancer Chemotherapy and Pharmacology
• 出版年：2014
• 出版时间：April 2014
• 年：2014
• 卷：73
• 期：4
• 页码：799-806
• 全文大小：227 KB
• 参考文献：1. Crew KD, Neugut AI (2006) Epidemiology of gastric cancer. World J Gastroenterol 12(3):354-62
  2. Chiang CY, Huang KH, Fang WL, Wu CW, Chen JH, Lo SS, Hsieh MC, Shen KH, Li AF, Niu DM, Chiou SH (2011) Factors associated with recurrence within 2?years after curative surgery for gastric adenocarcinoma. World J Surg 35(11):2472-478 CrossRef
  3. Benson AB (2008) Advanced gastric cancer: an update and future directions. Gastrointest Cancer Res 2(4 Suppl):S47–S53
  4. Ychou M, Astre C, Rouanet P, Fabre JM, Saint-Aubert B, Domergue J, Ribard D, Ciurana AJ, Janbon C, Pujol H (1996) A phase II study of 5-fluorouracil, leucovorin and cisplatin (FLP) for metastatic gastric cancer. Eur J Cancer 32A(11):1933-937 CrossRef
  5. Lin YC, Chen JS, Wang CH, Wang HM, Chang HK, Liaul CT, Yang TS, Liaw CC, Liu HE (2001) Weekly high-dose 5-fluorouracil (5-FU), leucovorin (LV) and bimonthly cisplatin in patients with advanced gastric cancer. Jpn J Clin Oncol 31(12):605-09 CrossRef
  6. Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S, Japan Clinical Oncology Group Study (JCOG9205) (2003) Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21(1):54-9 CrossRef
  7. Vanhoefer U, Rougier P, Wilke H, Ducreux MP, Lacave AJ, Van Cutsem E, Planker M, Santos JG, Piedbois P, Paillot B, Bodenstein H, Schmoll HJ, Bleiberg H, Nordlinger B, Couvreur ML, Baron B, Wils JA (2000) Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 18(14):2648-657
  8. Kim NK, Park YS, Heo DS, Suh C, Kim SY, Park KC, Kang YK, Shin DB, Kim HT, Kim HJ et al (1993) A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer 71(12):3813-818 CrossRef
  9. Budman DR, Meropol NJ, Reigner B, Creaven PJ, Lichtman SM, Berghorn E, Behr J, Gordon RJ, Osterwalder B, Griffin T (1998) Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine. J Clin Oncol 16(5):1795-802
  10. Ishitsuka H (2000) Capecitabine: preclinical pharmacology studies. Invest New Drugs 18(4):343-54 CrossRef
  11. Koizumi W, Saigenji K, Ujiie S, Terashima M, Sakata Y, Taguchi T, Clinical Study Group of Capecitabine (2003) A pilot phase II study of capecitabine in advanced or recurrent gastric cancer. Oncology 64(3):232-36 CrossRef
  12. Sakamoto J, Chin K, Kondo K, Kojima H, Terashima M, Yamamura Y, Tsujinaka T, Hyodo I, Koizumi W, Clinical Study Group of Capecitabine (2006) Phase II study of a 4-week capecitabine regimen in advanced or recurrent gastric cancer. Anticancer Drugs 17(2):231-36 CrossRef
  13. Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY (2004) A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol 15(9):1344-347 CrossRef
  14. Kim TW, Kang YK, Ahn JH, Chang HM, Yook JH, Oh ST, Kim BS, Lee JS (2002) Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer. Ann Oncol 13(12):1893-898 CrossRef
  15. 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 (2009) Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 20(4):666-73 CrossRef
  16. Woynarowski JM, Faivre S, Herzig MC, Arnett B, Chapman WG, Trevino AV, Raymond E, Chaney SG, Vaisman A, Varchenko M, Juniewicz PE (2000) Oxaliplatin-induced damage of cellular DNA. Mol Pharmacol 58(5):920-27
  17. Extra JM, Espie M, Calvo F, Ferme C, Mignot L, Marty M (1990) Phase I study of oxaliplatin in patients with advanced cancer. Cancer Chemother Pharmacol 25(4):299-03 CrossRef
  18. 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, J?ger E, Arbeitsgemeinschaft Internistische Onkologie (2008) 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 26(9):1435-442 CrossRef
  19. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR, Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358(1):36-6 CrossRef
  20. Park YH, Lee JL, Ryoo BY, Ryu MH, Yang SH, Kim BS, Shin DB, Chang HM, Kim TW, Yuh YJ, Kang YK (2008) Capecitabine in combination with Oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer. Cancer Chemother Pharmacol 61(4):623-29 CrossRef
  21. Xiang XJ, Zhang L, Qiu F, Yu F, Zhan ZY, Feng M, Yan J, Zhao JG, Xiong JP (2012) A phase ii study of capecitabine plus oxaliplatin as first-line chemotherapy in elderly patients with advanced gastric cancer. Chemotherapy 58(1):1-
  22. Luo HY, Xu RH, Wang F, Qiu MZ, Li YH, Li FH, Zhou ZW, Chen XQ (2010) Phase II trial of XELOX as first-line treatment for patients with advanced gastric cancer. Chemotherapy 56(2):94-00 CrossRef
  23. Yang T, Shen X, Tang X, Wei G, Zhang H, Du C, Xue X, Ma L, Nie M, Bi J (2011) Phase II trial of oxaliplatin plus oral capecitabine as first-line chemotherapy for patients with advanced gastric cancer. Tumori 97(4):466-72
  24. Dong NN, Wang MY, Zhang Q, Liu ZF (2009) Oxaliplatin combined with capecitabine as first-line chemotherapy for patients with advanced gastric cancer. Aizheng 28(4):412-15 (article in Chinese)
  25. Park YH, Kim BS, Ryoo BY, Yang SH (2006) A phase II study of capecitabine plus 3-weekly oxaliplatin as first-line therapy for patients with advanced gastric cancer. Br J Cancer 94(7):959-63 CrossRef
  26. Comella P, Massidda B, Filippelli G, Farris A, Natale D, Barberis G, Maiorino L, Palmeri S, Cannone M, Condemi G, Southern Italy Cooperative Oncology Group (2009) Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401. J Cancer Res Clin Oncol 135(2):217-26 CrossRef
  27. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205-16 CrossRef
  
• 作者单位：Yee Chao (1) (2)
  Jan-Sing Hsieh (3) (4)
  Hsien-Tang Yeh (5)
  Yu-Chieh Su (6)
  Cheng-Chung Wu (2) (7)
  Jen-Shi Chen (8)
  Cheng-Jeng Tai (10) (9)
  Li-Yuan Bai (11)
  Kun-Huei Yeh (12)
  Wu-Chou Su (13)
  Chung-Pin Li (14) (2)
  
  1. Department of Oncology Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  2. National Yang-Ming University School of Medicine, Taipei, Taiwan
  3. Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  4. Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  5. Department of Surgery, Lotung Poh-Ai Hospital, Yilan County, Taiwan
  6. Division of Hematology–Oncology, Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan
  7. Division of General Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
  8. Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan County, Taiwan
  10. Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taichung, Taiwan
  9. Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taichung, Taiwan
  11. Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
  12. Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
  13. Division of Hematology-Oncology, Department of Internal Medicine and Graduate Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  14. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, 11217, Taiwan
  
• ISSN：1432-0843

文摘

Purpose We evaluated the safety and efficacy of biweekly capecitabine in combination with oxaliplatin in previously untreated patients with locally advanced or metastatic gastric cancer. Methods Patients received oral capecitabine 1,000?mg/m2 twice daily on days 1-0 plus oxaliplatin 85?mg/m2 as a 2-h intravenous infusion on day 1, every 2?weeks (XELOX). The primary endpoint was overall response rate. Secondary endpoints included progression-free survival, overall survival, and toxicity. Results From March 2007 to October 2010, 46 patients were enrolled in this phase II study. The median age was 64?years (range 32-5). A total of 391 (median 7.5, range 1-9) cycles were delivered. Among the 41 patients evaluable for tumor response, 9 showed partial response and 25 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 22?% (95?% CI 10-2?%) and 20?% (95?% CI 9-4?%), respectively. In the ITT analysis, the progression-free survival and overall survival were 5.6?months (95?% CI 4.1-.3?months) and 8.0?months (95?% CI 6.3-0.1?months), respectively. The most common hematological toxicities were thrombocytopenia (35?%) and leucopenia (34?%), whereas the most common non-hematological toxicities were neuropathy (35?%), fatigue (33?%), diarrhea (27?%), vomiting (26?%), and hand-foot syndrome (25?%). Major grade 3- toxicities were anemia (11?%), diarrhea (9?%), and hand-foot syndrome (7?%). No patient died of treatment-related toxicities. Conclusions Although the biweekly XELOX regimen failed its primary response rate endpoint, it showed modest efficacy and an acceptable safety profile in the treatment of advanced gastric cancer.