Gastric cancer: Current status of diagnosis and treatment

Cancers

Volumn 5, Issue 1, 2013, Pages 48-63

  Takahashi, Tsunehiro ^a   Saikawa, Yoshiro ^a   Kitagawa, Yuko ^a  

^a KEIO UNIVERSITY   (Japan)

Author keywords

Chemotherapy; Gastric cancer; Molecular targeted therapy; Radiotherapy; Surgery

Indexed keywords

BEVACIZUMAB; CAPECITABINE; CETUXIMAB; CISPLATIN; DOCETAXEL; EPIRUBICIN; EVEROLIMUS; FLUORODEOXYGLUCOSE F 18; FLUOROURACIL; GIMERACIL PLUS OTERACIL POTASSIUM PLUS TEGAFUR; IRINOTECAN; LAPATINIB; OXALIPLATIN; PACLITAXEL; PANITUMUMAB; PLACEBO; RAMUCIRUMAB; TAXANE DERIVATIVE; TRASTUZUMAB;

ADVANCED CANCER; ALOPECIA; CANCER ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CANCER DIAGNOSIS; CANCER RADIOTHERAPY; CANCER STAGING; CANCER SURVIVAL; CANCER THERAPY; CHEMORADIOTHERAPY; COLORECTAL CANCER; DIARRHEA; DISEASE FREE SURVIVAL; DRUG FATALITY; ENDOSCOPIC SURGERY; GASTRECTOMY; GASTROINTESTINAL ENDOSCOPY; HEMATOLOGIC DISEASE; HUMAN; INTENSITY MODULATED RADIATION THERAPY; LAPAROSCOPIC SURGERY; LYMPH NODE DISSECTION; MOLECULARLY TARGETED THERAPY; NEUTROPENIA; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; POSITRON EMISSION TOMOGRAPHY; POSTOPERATIVE COMPLICATION; PROGRESSION FREE SURVIVAL; REVIEW; STOMACH CANCER; SURGICAL RISK; SURVIVAL RATE; SURVIVAL TIME;

EID: 84875246405     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers5010048     Document Type: Review

References (67)

1. Ferlay, J.; Shin, H.R.; Bray, F.; Forman, D.; Mathers, C.; Parkin, D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer 2010, 127, 2893-2917.
2. Ezoe, Y.; Muto, M.; Uedo, N.; Doyama, H.; Yao, K.; Oda, I.; Kaneko, K.; Kawahara, Y.; Yokoi, C.; Sugiura, Y.; et al. Magnifying narrowband imaging is more accurate than conventional white-lite imaging in diagnosis of gastric mucosal cancer. Gastroenterology 2011, 141, 2017-2025.
3. Nagahama, T.; Yao, K.; Maki, S.; Yasaka, M.; Takaki, Y.; Matsui, T.; Tanabe, H.; Iwashita, A.; Ota, A. Usefulness of magnifying endoscopy with narrow-band imaging for determining the horizontal extent of early gastric cancer when there is an unclear margin by chrmoendoscopy (with video). Gastrointest. Endosc. 2011, 74, 1259-1267.
4. Inoue, H.; Sasajima, K.; Kaga, M.; Sugaya, S.; Sato, Y.; Wada, Y.; Inui, M.; Satodate, H.; Kudo, S.E.; Kimura, S.; et al. Endoscopic in vivo evaluation of tissue atypia in the esophagus using a newly designed integrated endocytoscope: A pilot trial. Endoscopy 2006, 38, 891-895.
5. Kumagai, Y.; Kawada, K.; Yamazaki, S.; Iida, M.; Momma, K.; Odajima, H.; Kawachi, H.; Nemoto, T.; Kawano, T.; Takubo, K. Endocytoscopic observation for esophageal squamous cell carcinoma: Can biopsy histology be omitted? Dis. Esophagus 2009, 22, 505-512.
6. Inamoto, K.; Kouzai, K.; Ueeda, T.; Marukawa, T. CT virtual endoscopy of the stomach: Comparison study with gastric fiberscopy. Abdom. Imaging 2005, 30, 473-479.
7. Kole, A.C.; Plukker, J.T.; Nieweg, O.E.; Vaalburg, W. Positron emission tomography for staging of oesophageal and gastroesophageal malignancy. Br. J. Cancer 1998, 78, 521-527.
8. McAteer, D.; Wallis, F.; Couper, G.; Norton, M.; Welch, A.; Bruce, D.; Park, K.; Nicolson, M.; Gilbert, F.J.; Sharp, P. Evaluation of 18F-FDG positron emission tomography in gastric and oesophageal carcinoma. Br. J. Radiol. 1999, 72, 525-529.
9. Yoshikawa, K.; Kitaoka, H. Bone metastasis of gastric cancer. Jpn. J. Surg. 1983, 13, 173-176.
10. Smyth, E.; Scölder, H.; Strong, V.E.; Capanu, M.; Kelsen, D.P.; Coit, D.G.; Shah, M.A. A prospective evaluation of the utility of 2-deoxy-2-[(18) F] fluoro-D-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer. Cancer 2012, 118, 5481-5488.
11. Suittie, S.A.; Welch, A.E.; Park, K.G. Positron emission tomography for monitoring response to neoadjuvant therapy in patients with oesophageal and gastro-oesophageal junction carcinoma. Eur. J. Surg. Oncol. 2009, 35, 1019-1029.
12. Burke, E.C.; Karpeh, M.S.; Conlon, K.C.; Brennan, M.F. Laparoscopy in the management of gastric adenocarcinoma. Ann. Surg. 1997, 225, 262-267.
13. Lowy, A.M.; Mansfield, P.F.; Leach, S.D.; Ajani, J. Laparoscopic staging for gastric cancer. Surgery 1996, 119, 611-614.
14. Edge, S.B.; Byrd, D.R.; Compton, C.C.; Fritz, A.G.; Greene, F.L.; Trotti, A. AJCC Cancer Staging Manual, 7th ed.; Springer-Verlag: New York, NY, USA, 2009; pp. 117-126.
15. Bentrem, D.; Wilton, A.; Mazumdar, M.; Brennan, M.; Coit, D. The value of peritoneal cytology as a preoperative predictor in patients with gastric carcinoma undergoing a curative resection. Ann. Surg. Oncol. 2005, 12, 347-353.
16. Kodera, Y.; Yamamura, Y.; Shimizu, Y.; Torii, A.; Hirai, T.; Yasui, K.; Morimoto, T.; Kato, T. Peritoneal washing cytology: Prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection. J. Surg. Oncol. 1999, 72, 60-65.
17. Ono, H.; Kondo, H.; Gotoda, T.; Shirao, K.; Yamaguchi, H.; Saito, D.; Hosokawa, K.; Shimoda, T.; Yoshida, S. Endoscopic mucosal resection for treatment of early gastric cancer. Gut 2001, 48, 225-229.
18. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011, 14, 113-123.
19. Ono H. Endoscopic submucosal dissection for early gastric cancer. Chin. J. Dig. Dis. 2005, 6, 119-121.
20. Kodashima, S.; Fujishiro, M.; Yahagi, N.; Kakushima, N.; Ichinose, M.; Omata, M. Endoscopic submucosal dissection for gastric neoplasia: Experience with the flex-knife. Acta Gastroenterol. Belg. 2006, 69, 224-229.
21. Phillips, E.; Daykhovsky, L.; Carroll, B.; Gershman, A.; Grundfest, W.S. Laparoscopic cholecystectomy: Instrumentation and technique. J. Laparoendosc. Surg. 1990, 1, 3-15.
22. Jacobs, M.; Verdeja, J.C.; Goldstein, H.S. Minimally invasive colon resection (laparoscopic colectomy). Surg. Laparosc. Endosc. 1991, 1, 144-150.
23. Hüscher, C.G.; Lirici, M.M.; Chiodini, S. Laparoscopic liver resections. Semin. Laparosc. Surg. 1998, 5, 204-210.
24. Kitano, S.; Iso, Y.; Moriyama, M.; Sugimachi, K. Laparoscopy-assisted Billroth-I gasrtrectomy. Surg. Laparosc. Endosc. 1994, 4, 146-148.
25. Kanaya, S.; Haruta, S.; Kawamura, Y.; Yoshimura, F.; Inaba, K.; Hiramatsu, Y.; Ishida, Y.; Taniguchi, K.; Isogaki, J.; Uyama, I. Video: Laparosopy distinctive technique for suprapancreatic lymph node dissection: Medial approach for laparoscopic gastric cancer surgery. Surg. Endosc. 2011, 25, 3928-3929.
26. Ikeda, O.; Sakaguchi, Y.; Aoki, Y.; Harimoto, N.; Taomoto, J.; Masuda, T.; Ohga, T.; Adachi, E.; Toh, Y.; Okamura, T.; et al. Advantages of totally laparoscopic distal gastrectomy over laparoscopically assisted distal gastrectomy for gastric cancer. Surg. Endosc. 2009, 23, 2374-2379.
27. Hirahara, N.; Tanaka, T.; Yano, S.; Yamanoi, A.; Minari, Y.; Kawabata, Y.; Ueda, S.; Hira, E.; Yamamoto, T.; Nishi, T.; et al. Reconstruction of the gastrointestinal tract by hemi-double stapling method for the esophagus and jejunum using EEA OrVill in laparoscopic total gasrtectomy and proximal gastrectomy. Surg. Laparosc. Endosc. Percutan. Tech. 2011, 21, e11-e15.
28. Kitano, S.; Shiraishi, N.; Uyama, I.; Sugihara, K.; Tanigawa, N.; Japanese Laparoscopic Surgery Study Group. A multicenter study on oncologic outcome of laparoscopic gastrectomy for early cancer in Japan. Ann. Surg. 2007, 245, 68-72.
29. Kitano, S.; Shiraishi, N.; Fujii, K.; Yasuda, K.; Inomata, M.; Adachi, Y. A randomized controlled trial comparing open vs. laparoscopy-assisted distal gastrectomy for the treatment of early gastric cancer: An interim report. Surgery 2002, 131, S306-S311.
30. Huscher, C.G.; Mingoli, A.; Sgarzini, G.; Sansonetti, A.; di Paola, M.; Recher, A.; Ponzano, C. Laparoscopic versus open subtotal gastrectomy for distal gastric cancer: Five-year results of a randomized prospective trial. Ann. Surg. 2005, 241, 232-237.
31. Lee, J.H.; Han, H.S.; Lee, J.H. A prospective randomized study comparing open vs. laparoscopy-assisted distal gastrectiomy in early gastric cancer: Early result. Surg. Endosc. 2005, 19, 168-173.
32. Hayashi, H.; Ochiai, T.; Shimada, H.; Gunji, Y. Prospective randomized study of open versus laparoscopy-assisted distal gastrectiomy with extrperigastric lymph node dissection for early gastric cancer. Surg. Endosc. 2005, 19, 1172-1176.
33. Kim, Y.W.; Baik, Y.H.; Yun, Y.H.; Nam, B.H.; Kim, D.H.; Choi, I.J.; Bae, J.M. Improved quality of life outcomes after laparoscopy-assisted distal gastrectomy for early gastric cancer: Results of a prospective randomized clinical trial. Ann. Surg. 2008, 248, 721-727.
34. Katai, H.; Sasako, M.; Fukuda, H.; Nakamura, K.; Hiki, N.; Saka, M.; Yamaue, H.; Yoshikawa, T.; Kojima, K.; JCOG Gastric Cancer Surgical Study Group. Safety and feasibility of laparoscopy-assisted distal gastrectomy with suprapancreatic nodal dissection for clinical stage I gastric cancer: A multicenter phase II trial (JCOG0703). Gastric Cancer 2010, 13, 238-244.
35. Kim, H.H.; Hyung, W.J.; Cho, G.S.; Kim, M.C.; Han, S.U.; Kim, W.; Ryu, S.W.; Lee, H.J.; Song, K.Y. Morbidity and motality of laparoscopic gastrectomy versus open gastrectomy for gastric cancer: An interim report-a phase III multicenter, prospective, randomized trial (KLASS Trial). Ann. Surg. 2010, 251, 417-420.
36. Pietrabissa, A.; Sbrana, F.; Morelli, L.; Badessi, F.; Pugliese, L.; Vinci, A.; Klersy, C.; Spinoglio, G. Overcoming the challenges of single-incision cholecystectomy with robotic single-site technology. Arch. Surg. 2012, 147, 709-714.
37. Woo, R.; Le, D.; Krummel, T.M.; Albanese, C. Robot-assisted pediatric surgery. Am. J. Surg. 2004, 188, 27S-37S.
38. Lowery, W.J.; Leath, C.A., 3rd; Robinson, R.D. Robotic surgery applications in tne management of gynecologic malignancies. J. Surg. Oncol. 2012, 105, 481-487.
39. Nix, J.; Smith, A.; Kurpad, R.; Nielsen, M.E.; Wallen, E.M.; Pruthi, R.S. Prospective randomized controlled trial of robotic versus open radical cystectomy of bladder cancer: Perioperative and pathologic results. Eur. Urol. 2010, 57, 196-201.
40. Cuschieri, A.; Weeden, S.; Fielding, J.; Bancewicz, J.; Craven, J.; Joypaul, V.; Sydes, M.; Fayers, P. Patient survival after D1 and D2 resection for gastric cancer: Long-term results of the MRC randomized surgical trial. Surgical Co-operative Group. Br. J. Cancer 1999, 79, 1522-1530.
41. Hartgrink, H.H.; van de Velde, C.J.; Putter, H.; Bonenkamp, J.J.; Klein Kranenbarg, E.; Songun, I.; Welvaart, K.; van Krieken, J.H.; Meijer, S.; Plukker, J.T.; et al. Extended lymph node dissection for gastric cancer: Who may benefit? Final results of the randomized Dutch Gastric Cancer Group Trial. J. Clin. Oncol. 2004, 22, 2069-2077.
42. Sano, T.; Sasako, M.; Yamamoto, S.; Nashimoto, A.; Kurita, A.; Hiratsuka, M.; Tsujinaka, T.; Kinoshita, T.; Arai, K.; Yamamura, Y.; et al. Gastric cancer surgery: Morbidity and mortality results from a prospective randomized controlled trial comparing D2 and extended para-aortic lymphadenectomy-Japan Clinical Oncology Study Group Study 9501. J. Clin. Oncol. 2004, 22, 2767-2773.
43. Sasako, M.; Sano, T.; Yamamoto, S.; Kurokawa, Y.; Nashimoto, A.; Kurita, A.; Hiratsuka, M.; Tsujinaka, T.; Kinoshita, T.; Arai, K.; et al. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N. Engl. J. Med. 2008, 359, 453-462.
44. Kang, Y.K.; Kang, W.K.; Shin, D.B.; Chen, J.; Xiong, J.; Wang, J.; Lichinitser, M.; Guan, Z.; Khasanov, R.; Zheng, L.; et al. 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, 663-673.
45. Ajani, J.A.; Rodriguez, W.; Bodoky, G.; Moiseyenko, V.; Lichinitser, M.; Gorbunova, V.; Vynnychenko, I.; Garin, A.; Lang, I.; Falcon, S. 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. 2010, 28, 1547-1553.
46. Van Cutsem, E.; Moiseyenko, V.M.; Tjulandin, S.; Majlis, A.; Constenla, M.; Boni, C.; Rodrigues, A.; Fodor, M.; Chao, Y.; Voznyi, E.; et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line chemotherapy for advanced gastric cancer: A report of the V325 study group. J. Clin. Oncol. 2006, 24, 4991-4997.
47. Koizumi, W.; Narahara, H.; Hara, T.; Takagane, A.; Akiya, T.; Takagi, M.; Miyashita, K.; Nishizaki, T.; Kobayashi, O.; Takiyama, W.; et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): A phase III trial. Lancet Oncol. 2008, 9, 215-221.
48. Cunningham, D.; Starling, N.; Rao, S.; Iveson, T.; Nicolson, M.; Coxon, F.; Middleton, G.; Daniel, F.; Oates, J.; Norman, A.R.; et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N. Engl. J. Med. 2008, 358, 36-46.
49. Macdonald, J.S.; Smalley, S.R.; Benedetti, J.; Hundahl, S.A.; Estes, N.C.; Stemmermann, G.N.; Haller, D.G.; Ajani, J.A.; Gunderson, L.L.; Jessup, J.M.; et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N. Engl. J. Med. 2001, 345, 725-730.
50. Lee, J.; Lim, D.H.; Kim, S.; Park, S.H.; Park, J.O.; Park, Y.S.; Lim, H.Y.; Choi, M.G.; Sohn, T.S.; Noh, J.H.; et al. Phase III trial comparing capecitabine plus cisplatin vesus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: The ARTIST trial. J. Clin. Oncol. 2012, 30, 268-273.
51. Cunningham, D.; Allum, W.H.; Stenning, S.P.; Thompson, J.N.; van de Velde, C.J.; Nicolson, M.; Scarffe, J.H.; Lofts, F.J.; Falk, S.J.; Iveson, T.J.; et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N. Engl. J. Med. 2006, 355, 11-20.
52. Dikken, J.L.; van Sandick, J.W.; Mauritis Swellengrebel, H.A.; Lind, P.A.; Putter, H.; Jansen, E.P.; Boot, H.; van Grieken, N.C.; van de Velde, C.J.; Verheij, M.; et al. Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS). BMC Cancer 2011, 11, 329.
53. Sasako, M.; Sakuramoto, S.; Katai, H.; Kinoshita, T.; Furukawa, H.; Yamaguchi, T.; Nashimoto, A.; Fujii, M.; Nakajima, T.; Ohashi, Y. Five-year outcomes of randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J. Clin. Oncol. 2011, 29, 4387-4393.
54. Bang, Y.J.; Kim, Y.W.; Yang, H.K.; Chung, H.C.; Park, Y.K.; Lee, K.H.; Lee, K.W.; Kim, Y.H.; Noh, S.I.; Cho, J.Y.; et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): A phase 3 open-label, randomized controlled trial. Lancet 2012, 379, 315-321.
55. Childs, D.S., Jr.; Moetrel, C.G.; Holbrook, M.A.; Reitemeier, R.J.; Colby, M., Jr. Treatment of unresectable adenocarcinomas of the stomach with a combination of 5-fluorouracil and radiation. Am. J. Roentgenol. Ther. Nucl. Med. 1968, 102, 541-544.
56. Falkson, G.; Falkson, H.C. Fluorouracil and radiotherapy in gastrointestinal cancer. Lancet 1969, 2, 1252-1253.
57. Klaassen, D.J.; Maclntyre, J.M.; Catton, G.E.; Engstrom, P.F.; Moertel, C.G. Treatment of locally unresectable cancer of the stomach and pancreas: A randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil-An Eastern Cooperative Oncology Group Study. J. Clin. Oncol. 1985, 3, 373-378.
58. Saikawa, Y.; Kubota, T.; Kumagai, K.; Nakamura, R.; Kumai, K.; Shigematsu, N.; Kubo, A.; Kitajima, M.; Kitagawa, Y. Phase II study of chemoradiotherapy with S-1 and low-dose cisplatin for inoperable advanced gastric cancer. Int. J. Radiat. Oncol. Biol. Phys. 2007, 71, 173-179.
59. Yoshikawa, T.; Tsuburaya, A.; Hirabayashi, N.; Yoshida, K.; Nagata, N.; Kodera, Y.; Takahashi, N.; Oba, K.; Kimura, M.; Ishikura, S.; et al. A phase I study of palliative chemoradiation therapy with paclitaxel and cisplatin for local symptoms due to an unresectable primary advanced or locally recurrent gastric adenocarcinoma. Cancer Chemother. Pharmacol. 2009, 64, 1071-1077.
60. Hashimoto, K.; Mayahara, H.; Takashima, A.; Nakajima, T.E.; Kato, K.; Hamaguchi, T.; Ito, Y.; Yamada, Y.; Kagami, Y.; Itami, J.; et al. Palliative radiation therapy for hemorrhage of unresectable gastric cancer: A single institute experience. J. Cancer Res. Clin. Oncol. 2009, 135, 1117-1123.
61. Dawood, S.; Broglio, K.; Buzdar, A.U.; Hortobagyi, G.N.; Giordano, S.H. Prognosis of women with metaplastic breast cancer by HER2 status and trastuzumab treatment: An institutional-based review. J. Clin. Oncol. 2010, 28, 92-98.
62. Terashima, M.; Kitada, K.; Ochiai, A.; Ichikawa, W.; Kurahashi, I.; Sakuramoto, S.; Katai, H.; Sano, T.; Imamura, H.; Sasako, M.; et al. Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in Stage II/III gastric cancer. Clin. Cancer Res. 2012, 18, 5992-6000.
63. Janjigian, Y.Y.; Werner, D.; Pauligk, C.; Steinmetz, K.; Kelsen, D.P.; Jäger, E.; Altmannsberger, H.M.; Robinson, E.; Tafe, L.J.; Tang, L.H.; et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: A European and USA international collaborative analysis. Ann. Oncol. 2012, 23, 2656-2662.
64. Bang, Y.J.; van Cutsem, E.; Feyereislova, A.; Chung, H.C.; Shen, L.; Sawaki, A.; Lordick, F.; Ohtsu, A.; Omuro, Y.; Satoh, T.; 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 2010, 376, 687-697.
65. Ohtsu, A.; Shah, M.A.; van Cutsem, E.; Rha, S.Y.; Sawaki, A.; Park, S.R.; Lim, H.Y.; Yamada, Y.; Wu, J.; Langer, B.; 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. 2011, 29, 3968-3976.
66. Chau, I.; Okines, A.F.; Castro, D.G.; Saffery, Y.; Barbachano, A.; Wotherspoon, L.; Puckey, S.; Hulkki Wilson, F.Y.; Coxon, G.W.; Middleton, D.R.; et al. REAL3: A multicenter randomized phase II/III trial of epirubicin, oxaliplatin, and capecitabine (EOC) versus modified (m) EOC plus panitumumab (P) in advanced oesophagogastric (OG) cancer-Response rate (RR), toxicity, and molecular analysis from phase II. J. Clin. Oncol. 2011, 29, Abstract 4131.
67. Lordick, F.; Bodoky, G.; Chung, H.; Kurteva, G.; Kang, Y.; Oh, S.C.; Salman, P.; Goette, H.; Melezinkova, H.; Moehler, M. Cetuximab in combination with capecitabine and cisplatin as first-line treatment in advanced gastric cancer: Randomized controlled phase III EXPAND study. Ann. Oncol. 2012, 23, LBA3.