Capecitabine in gastric cancer

Expert Review of Anticancer Therapy

Volumn 11, Issue 12, 2011, Pages 1791-1806

  Bang, Yung Jue ^a  

^a Seoul National University College of Medicine   (South Korea)

Author keywords

5 fluorouracil; adjuvant; capecitabine; cisplatin; docetaxel; epirubicin; gastric cancer; oxaliplatin; palliative; safety

Indexed keywords

BEVACIZUMAB; CAPECITABINE; CELECOXIB; CETUXIMAB; CISPLATIN; DOCETAXEL; EPIRUBICIN; FLUOROURACIL; GIMERACIL PLUS OTERACIL POTASSIUM PLUS TEGAFUR; IRINOTECAN; LAPATINIB; OXALIPLATIN; PACLITAXEL; PANITUMUMAB; SIMVASTATIN; TRASTUZUMAB;

ADVANCED CANCER; ALOPECIA; ANEMIA; ANOREXIA; ASTHENIA; CANCER COMBINATION CHEMOTHERAPY; CANCER SURGERY; CANCER SURVIVAL; CHEMOTHERAPY INDUCED EMESIS; COLORECTAL CANCER; DIARRHEA; DISEASE ASSOCIATION; DISEASE FREE SURVIVAL; DOSE RESPONSE; DRUG ABSORPTION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; ESOPHAGUS CANCER; FATIGUE; FEBRILE NEUTROPENIA; GASTRECTOMY; GASTROINTESTINAL DISEASE; GASTROINTESTINAL TOXICITY; GRANULOCYTOPENIA; HAND FOOT SYNDROME; HEMATOLOGIC DISEASE; HUMAN; INFECTION; INTERMETHOD COMPARISON; LETHARGY; LEUKOPENIA; LOW DRUG DOSE; METASTASIS; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; REVIEW; STOMACH CANCER; STOMATITIS; THROMBOCYTOPENIA; VOMITING;

ANTIMETABOLITES, ANTINEOPLASTIC; CLINICAL TRIALS AS TOPIC; DEOXYCYTIDINE; FLUOROURACIL; HUMANS; STOMACH NEOPLASMS; TREATMENT OUTCOME;

EID: 82355181398     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.11.172     Document Type: Review

References (83)

1. Cunningham D, Okines AF, Ashley S. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N. Engl. J. Med. 362(9), 858-859 (2010).
2. Wagner AD, Unverzagt S, Grothe W et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst. Rev. 3, CD004064 (2010).
3. Kim NK, Park YS, Heo DS et al. 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), 3813-3818 (1993).
4. Ohtsu A, Shimada Y, Shirao K et al. 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), 54-59 (2003).
5. Vanhoefer U, Rougier P, Wilke H et al. 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), 2648-2657 (2000). (Pubitemid 30465650)
6. Van Cutsem E, Moiseyenko VM, Tjulandin S et al. 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. 24(31), 4991-4997 (2006). (Pubitemid 46631401)
7. Montagnani F, Turrisi G, Marinozzi C et al. Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis. Gastric Cancer 14(1), 50-55 (2011).
8. Carrato A, Gallego-Plazas J, Guillén-Ponce C. Capecitabine plus oxaliplatin for the treatment of colorectal cancer. Expert Rev. Anticancer. Ther. 8(2), 161-174 (2008). (Pubitemid 351385906)
9. Schüller J, Cassidy J, Dumont E et al. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother. Pharmacol. 45(4), 291-297 (2000). (Pubitemid 30151522)
10. Endo M, Shinbori N, Fukase Y et al. Induction of thymidine phosphorylase expression and enhancement of efficacy of capecitabine or 5-deoxy-5- fluorouridine by cyclophosphamide in mammary tumor models. Int. J. Cancer 83(1), 127-134 (1999). (Pubitemid 29409488)
11. Ishitsuka H. Capecitabine: preclinical pharmacology studies. Invest. New Drugs 18(4), 343-354 (2000).
12. Reigner B, Blesch K, Weidekamm E. Clinical pharmacokinetics of capecitabine. Clin. Pharmacokinet. 40(2), 85-104 (2001). (Pubitemid 32242792)
13. Judson IR, Beale PJ, Trigo JM et al. A human capecitabine excretion balance and pharmacokinetic study after administration of a single oral dose of 14C-labelled drug. Invest. New Drugs. 17(1), 49-56 (1999). (Pubitemid 29452747)
14. Evans TR, Pentheroudakis G, Paul J et al. A Phase I and pharmacokinetic study of capecitabine in combination with epirubicin and cisplatin in patients with inoperable oesophago-gastric adenocarcinoma. Ann. Oncol. 3(9), 1469-1478 (2002).
15. Reigner B, Watanabe T, Schüller J et al. Pharmacokinetics of capecitabine (Xeloda) in Japanese and Caucasian patients with breast cancer. Cancer Chemother. Pharmacol. 52(3), 193-201 (2003). (Pubitemid 37204532)
16. Poole C, Gardiner J, Twelves C et al. Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients. Cancer Chemother. Pharmacol. 49(3), 225-234 (2002). (Pubitemid 34185596)
17. Camidge R, Reigner B, Cassidy J et al. Significant effect of capecitabine on the pharmacokinetics and pharmacodynamics of warfarin in patients with cancer. J. Clin. Oncol. 23(21), 4719-4725 (2005). (Pubitemid 46224075)
18. Kim TW, Kang YK, Ahn JH et al. Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer. Ann. Oncol. 13(12), 1893-1898 (2002). (Pubitemid 36049952)
19. Hong YS, Song SY, Lee SI et al. A Phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann. Oncol. 15(9), 1344-1347 (2004). (Pubitemid 39295021)
20. Lee JL, Kang YK, Kang HJ et al. A randomised multicentre Phase II trial of capecitabine vs S-1 as first-line treatment in elderly patients with metastatic or recurrent unresectable gastric cancer. Br. J. Cancer 99(4), 584-590 (2008).
21. Sakamoto J, Chin K, Kondo K et al. Phase II study of a 4-week capecitabine regimen in advanced or recurrent gastric cancer. Anticancer Drugs 17(2), 231-236 (2006).
22. Moehler M, Kanzler S, Geissler M et al. Arbeitsgemeinschaft Internistische Onkologie, Germany. A randomized multicenter Phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann. Oncol. 21(1), 71-77 (2010).
23. Salah-Eldin MA, Ebrahim MA, AL-Ashry MS. Phase II study of capecitabine plus cisplatin in patients with gastric cancer. Anticancer Drugs 20(3), 191-196 (2009).
24. Yun J, Lee J, Park SH et al. A randomised Phase II study of combination chemotherapy with epirubicin, cisplatin and capecitabine (ECX) or cisplatin and capecitabine (CX) in advanced gastric cancer. Eur. J. Cancer 46(5), 885-891 (2010).
25. Dong N, Jiang W, Li H et al. Triweekly oxaliplatin plus oral capecitabine as first-line chemotherapy in elderly patients with advanced gastric cancer. Am. J. Clin. Oncol. 32(6), 559-563 (2009).
26. Jatoi A, Murphy BR, Foster NR et al. 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. 17(1), 29-34 (2006). (Pubitemid 43033836)
27. Liu C, Sun Q, Hang X, Zhong B, Wang D. Multicenter Phase II study of capecitabine plus oxaliplatin as a first-line therapy in Chinese patients with advanced gastric cancer. Anticancer Drugs 19(8), 825-831 (2008).
28. Luo HY, Xu RH, Wang F et al. Phase II trial of XELOX as first-line treatment for patients with advanced gastric cancer. Chemotherapy 56(2), 94-100 (2010).
29. Park YH, Lee JL, Ryoo BY et al. Capecitabine in combination with oxaliplatin (XELOX) as a first-line therapy for advanced gastric cancer. Cancer Chemother. Pharmacol. 61(4), 623-629 (2008).
30. Kang YK, Ryu MH, Yoo C et al. Phase I/II study of a combination of docetaxel, capecitabine, and cisplatin (DXP) as first-line chemotherapy in patients with advanced gastric cancer. Cancer Chemother. Pharmacol. 67(6), 1435-1443 (2011).
31. Evans D, Miner T, Akerman P et al. A Phase I study of docetaxel, oxaliplatin, and capecitabine in patients with metastatic gastroesophageal cancer. Am. J. Clin. Oncol. 30(4), 346-349 (2007). (Pubitemid 47356677)
32. Sym SJ, Ryu MH, Kang HJ et al. Phase I study of 3-weekly docetaxel, capecitabine and oxaliplatin combination chemotherapy in patients with previously untreated advanced gastric cancer. Cancer Chemother. Pharmacol. 66(2), 373-380 (2010).
33. Andersen M, Schonnemann KR, Yilmaz M et al. Phase I study of docetaxel, oxaliplatin and capecitabine (TEX) as first line therapy to patients with advanced gastro-oesophageal cancer. Acta Oncol. 49(8), 1246-1252 (2010).
34. Goel G, Jauhri M, Negi A, Aggarwal S. Feasibility study of docetaxel, oxaliplatin and capecitabine combination regimen in advanced gastric or gastroesophageal adenocarcinoma. Hematol. Oncol. Stem Cell Ther. 3(2), 55-59 (2010).
35. Malik I, Bernal P, Byrd J. A Phase I study of docetaxel, oxaliplatin, & capecitabine (DOC) as first-line therapy of patients with locally advanced or metastatic adenocarcinoma of stomach and GE junction. Cancer Invest. 28(8), 833-838 (2010).
36. Van Cutsem E, Boni C, Tabernero J et al. Randomized Phase II study (GATE study) of docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer. J. Clin. Oncol. 29(Suppl.) (2011) (Abstract 4018).
37. Chun JH, Kim HK, Lee JS et al. Weekly docetaxel in combination with capecitabine in patients with metastatic gastric cancer. Am. J. Clin. Oncol. 28(2), 188-194 (2005). (Pubitemid 40514433)
38. Giordano KF, Jatoi A, Stella PJ et al. Docetaxel and capecitabine in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction: a Phase II study from the North Central Cancer Treatment Group. Ann. Oncol. 17(4), 652-656 (2006).
39. Park YH, Ryoo BY, Choi SJ et al. A Phase II study of capecitabine and docetaxel combination chemotherapy in patients with advanced gastric cancer. Br. J. Cancer 90(7), 1329-1333 (2004). (Pubitemid 38586256)
40. Thuss-Patience PC, Kretzschmar A, Dogan Y et al. Docetaxel and capecitabine for advanced gastric cancer: investigating dose-dependent efficacy in two patient cohorts. Br. J. Cancer 105(4), 505-512 (2011).
41. Tebbutt NC, Cummins MM, Sourjina T et al. Randomised, non-comparative Phase II study of weekly docetaxel with cisplatin and 5-fluorouracil or with capecitabine in oesophagogastric cancer: the AGITG ATTAX trial. Br. J. Cancer 102(3), 475-481 (2010).
42. Kohne C-H, De Greve J, Hartmann JT et al. Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann. Oncol. 19, 920-926 (2008). (Pubitemid 351627308)
43. Fuchs CS, Marshall J, Mitchell E et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J. Clin. Oncol. 25, 4779-4786 (2007). (Pubitemid 350086481)
44. Koopman M, Antonini NF, Douma J et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a Phase III randomised controlled trial. Lancet 370(9582), 135-142 (2007). (Pubitemid 47042893)
45. Reinacher-Schick AC, Kubicka S, Freier W et al. Activity of the combination of bevacizumab (Bev) with capecitabine/ irinotecan (CapIri/Bev) or capecitabine/ oxaliplatin (CapOx/Bev) in advanced colorectal cancer (ACRC): a randomized Phase II study of the AIO Colorectal Study Group (AIO trial 0604). J. Clin. Oncol. 26 (2008) (Abstract 4030).
46. Baek JH, Kim JG, Jeon SB et al. Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer. Br. J. Cancer 94(10), 1407-1411 (2006). (Pubitemid 43772274)
47. Oh SC, Sur HY, Sung HJ et al. A Phase II study of biweekly dose-intensified oral capecitabine plus irinotecan (bXELIRI) for patients with advanced or metastatic gastric cancer. Br. J. Cancer 96(10), 1514-1519 (2007). (Pubitemid 46762953)
48. Cho EK, Lee WK, Im SA et al. A Phase II study of epirubicin, cisplatin and capecitabine combination chemotherapy in patients with metastatic or advanced gastric cancer. Oncology 68(4-6), 333-340 (2005).
49. Ocvirk J, Reberšek M, Skof E, Hlebanja Z, Boc M. Randomized prospective Phase II study to compare the combination chemotherapy regimen epirubicin, cisplatin, and 5-fluorouracil with epirubicin, cisplatin, and capecitabine in patients with advanced or metastatic gastric cancer. Am. J. Clin. Oncol. doi:10.1097/ COC.0b013e31820dc0b0 (2011) (Epub aheaad of print).
50. Schonnemann KR, Jensen HA, Yilmaz M et al. Phase II study of short-time oxaliplatin, capecitabine and epirubicin (EXE) as first-line therapy in patients with non-resectable gastric cancer. Br. J. Cancer 99(6), 858-861 (2008).
51. Xiang XJ, Qiu F, Xiong JP et al. A Phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) as first-line chemotherapy in advanced gastric cancer: a Chinese single-center experience. Chemotherapy 56(3), 171-177 (2010).
52. Kang YK, Kang WK, Shin DB et al. Capecitabine-cisplatin versus 5-fluorouracil/ cisplatin as first-line therapy in patients with advanced gastric cancer: a randomized Phase III noninferiority trial. Ann. Oncol. 20(4), 666-673 (2009).
53. Cunningham D, Starling N, Rao S et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N. Engl. J. Med. 358(1), 36-46 (2008).
54. Bang YJ, Van Cutsem E, Feyereislova A et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a Phase 3, open-label, randomised controlled trial. Lancet 376(9749), 687-697 (2010).
55. Ohtsu A, Shah MA, Van Cutsem E et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized double-blind placebo-controlled Phase III study. J. Clin. Oncol. 29(30), 3968-7620 (2011).
56. Okines AF, Norman AR, McCloud P et al. 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. 20(9), 1529-1534 (2009).
57. Okines AF, Ashley SE, Cunningham D et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dose-finding study for the prospective multicenter, randomized, Phase II/III REAL-3 trial. J. Clin. Oncol. 28(25), 3945-3950 (2010).
58. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 11(5), 439-449 (2010).
59. Wu CW, Hsiung CA, Lo SS et al. Nodal dissection for patients with gastric cancer: a randomised controlled trial. Lancet Oncol. 7(4), 309-315 (2006).
60. Okines A, Verheij M, Allum W, Cunningham D, Cervantes A. ESMO Guidelines Working Group. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 21(Suppl. 5), v50-v54 (2010).
61. National Comprehensive Cancer Network. NCCN Cancer Guidelines, gastric cancer, 2011, version 2 (2011).
62. Cunningham D, Chua YJ. East meets west in the treatment of gastric cancer. N. Engl. J. Med. 357(18), 1863-1865 (2007). (Pubitemid 350044810)
63. Macdonald JS, Smalley SR, Benedetti J et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N. Engl. J. Med. 345(10), 725-730 (2001).
64. Cunningham D, Allum WH, Stenning SP et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N. Engl. J. Med. 355(1), 11-20 (2006).
65. Ychou M, Boige V, Pignon JP et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter Phase III trial. J. Clin. Oncol. 29(13), 1715-1721 (2011).
66. Sakuramoto S, Sasako M, Yamaguchi T et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N. Engl. J. Med. 357(18), 1810-1820 (2007). (Pubitemid 350044801)
67. Bang Y-J, Kim Y, Yang H et al. Adjuvant capecitabine and oxaliplatin for gastric cancer: Results of the Phase III CLASSIC trial. J. Clin. Oncol. 29(Suppl.) (2011) (Abstract LBA4002).
68. Burzykowski T, Bang Y: on behalf of the GASTRIC project. Disease-free survival as a surrogate endpoint for overall survival in an adjuvant trial of curatively resected stomach cancer using individual patient data meta-analysis. J. Clin. Oncol. 27, 15s (2009) (Abstract 4517).
69. Dikken JL, van Sandick JW, Maurits Swellengrebel H et al. Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS). BMC Cancer 11, 329 (2011).
70. Lee J, Kang W, Lim D et al. Phase III trial of adjuvant capecitabine/cisplatin (XP) compared with capecitabine/cisplatin/RT (XPRT) in resected gastric cancer with D2 nodal dissection (ARTIST trial): safety analysis. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium. CA, USA, 20-22 January 2009.
71. Van Cutsem E, Findlay M, Osterwalder B et al. Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomized Phase II study. J. Clin. Oncol. 18(6), 1337-1345 (2000). (Pubitemid 30159854)
72. Cassidy J, Twelves C, van Cutsem E et al. First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann. Oncol. 13(4), 566-575 (2002). (Pubitemid 34461140)
73. Cassidy J, Clarke S, Diaz Rubio E et al. A randomized Phase III study of capecitabine plus oxaliplatin (XELOX) versus fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as first-line therapy for metastatic colorectal cancer. J. Clin. Oncol. 26, 2006-2012 (2008).
74. Rothenberg ML, Cox JV, Butts C et al. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized Phase III noninferiority study. Ann. Oncol. 19, 1720-1726 (2008).
75. Starling N, Rao S, Cunningham D et al. Thromboembolism in patients with advanced gastroesophageal cancer treated with anthracycline, platinum, and fluoropyrimidine combination chemotherapy: a report from the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group. J. Clin. Oncol. 27(23), 3786-3793 (2009).
76. Haller DG, Cassidy J, Clarke SJ et al. Potential regional differences for the tolerability profiles of fluoropyrimidines. J. Clin. Oncol. 26(13), 2118-2123 (2008).
77. Norman G, Soares M, Peura P et al. Capecitabine for the treatment of advanced gastric cancer. Health Technol. Assess. 14(Suppl. 2), 11-17 (2010).
78. Van Cutsem E, Van de Velde C, Roth A et al. Expert opinion on management of gastric and gastro-oesophageal junction adenocarcinoma on behalf of the European Organisation for Research and Treatment of Cancer (EORTC)- gastrointestinal cancer group. Eur. J. Cancer 44(2), 182-194 (2008).
79. Wong R, Cunningham D. Optimising treatment regimens for the management of advanced gastric cancer. Ann. Oncol. 20(4), 605-608 (2009).
80. Ajani JA, Rodriguez W, Bodoky G et al. Multicenter Phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J. Clin. Oncol. 28, 1547-1553 (2010).
81. Dank M, Zaluski J, Barone C et al. Randomized Phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann. Oncol. 19(8), 1450-1457 (2008).
82. Park SH, Lim DH, Park K et al. A multicenter, randomized Phase III trial comparing second-line chemotherapy (SLC) plus best supportive care (BSC) with BSC alone for pretreated advanced gastric cancer (AGC). J. Clin. Oncol. 29 (2011) (Abstract 4004).
83. Kang HJ, Chang HM, Kim TW et al. A Phase II study of paclitaxel and capecitabine as a first-line combination chemotherapy for advanced gastric cancer. Br. J. Cancer 98(2), 316-322 (2008). (Pubitemid 351161266)