Neoadjuvant chemotherapy versus none for resectable gastric cancer.

BACKGROUND Gastric cancer is a major cause of cancer death, and many patients are only diagnosed when the cancer has reached an advanced stage. Neoadjuvant chemotherapy (NAC), that is, chemotherapy administered shortly before surgical treatment, could provide a method of increasing the possibility of complete resection and survival. OBJECTIVES To evaluate the effect of neoadjuvant chemotherapy versus none for patients with resectable gastric cancer in terms of efficacy and toxicity. SEARCH STRATEGY Electronic databases including Cochrane Library, MEDLINE, EMBASE, CancerLit, Chinese Biomedical Literature Database (CBMDISC) and ongoing clinical trials as well as handsearching of conference proceedings, were searched to retrieve relevant data. SELECTION CRITERIA Randomized controlled clinical trials of neoadjuvant chemotherapy on resectable gastric cancer. DATA COLLECTION AND ANALYSIS We identified a total of 36 published citations or meeting abstracts. Thirty-two items were excluded. Of the four remaining studies, three stated random allocation but the method of randomization was unclear. Two of these employed allocation concealment by sealed envelope which was controlled by an independent party. None of the trials was double blind. All trials presented a detailed description of the number of withdrawals, dropouts and losses to follow-up. MAIN RESULTS Of the four clinical trials enrolled, there were 250 and 332 cases in total, with 106 and 126 deaths at the end of follow-up in the NAC and control group, respectively. The OR (odds ratio) was 1.05 (95%CI: 0.73-1.50), which was not statistically significant. Of the evaluable 129 patients receiving NAC, 28.7% demonstrated either a complete or a partial response. Two studies of NAC in resectable gastric cancer had resection rate data available for analysis The R0 resection rate in the NAC group was comparable to that in the control (OR: 0.96 (95%CI: 0.51-1.83)). The morbidity and mortality of NAC varied with the regimens used preoperatively. Of the 129 patients included in the analyzed studies, some acceptable toxicity was observed. AUTHORS' CONCLUSIONS There is no definite evidence of the effectiveness of NAC in resectable gastric cancer, in terms of improvements in patient survival, in the trials we reviewed. Neoadjuvant chemotherapy should not be used routinely in clinical setting until further results from randomized clinical are available. Neoadjuvant chemotherapy of gastric cancer should be applied under the framework of clinical trials.

[1]  D. Cunningham,et al.  Perioperative chemotherapy in operable gastric and lower oesophageal cancer: Final results of a randomised, controlled trial (the MAGIC trial, ISRCTN 93793971) , 2005 .

[2]  H. Putter,et al.  Neo-adjuvant chemotherapy for operable gastric cancer: long term results of the Dutch randomised FAMTX trial. , 2004, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[3]  Y. Nio,et al.  A randomized consent design trial of neoadjuvant chemotherapy with tegafur plus uracil (UFT) for gastric cancer--a single institute study. , 2004, Anticancer research.

[4]  Kwok-Kin Wong,et al.  Complications of gastrectomy following CPT-11-based neoadjuvant chemotherapy for gastric cancer , 2003, Journal of Gastrointestinal Surgery.

[5]  H. Höfler,et al.  Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy , 2003, Cancer.

[6]  J. Sakamoto Neoadjuvant chemotherapy: a standard treatment for locally advanced gastric cancer in the near future? , 2003, Gastric Cancer.

[7]  D. Cunningham,et al.  45 Perioperative chemotherapy in operable gastric and lower oesophageal cancer: a randomised, controlled trial of the UK NCRI upper GI clinical studies group (the MAGIC trial, ISRCTN 93793971) , 2003 .

[8]  C. Leichman,et al.  Definitive and neoadjuvant therapies for esophageal and gastroesophageal junction tumors: a look back and toward the future. , 2003, Seminars in oncology.

[9]  C. V. D. van de Velde,et al.  The gastric cancer treatment controversy. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  M. Miyazaki,et al.  Neoadjuvant chemotherapy with CDDP and 5-fluorouracil for gastric cancer with serosal invasion. , 2003, Oncology reports.

[11]  S. Thompson,et al.  How should meta‐regression analyses be undertaken and interpreted? , 2002, Statistics in medicine.

[12]  H. Tao,et al.  Effect of preoperative regional artery chemotherapy on proliferation and apoptosis of gastric carcinoma cells. , 2002, World journal of gastroenterology.

[13]  Douglas G Altman,et al.  Statistical methods for assessing the influence of study characteristics on treatment effects in ‘meta‐epidemiological’ research , 2002, Statistics in medicine.

[14]  Gang Su,et al.  Local injection of M-CH combined with i.p. hyperthermic hypo-osmolar infusion is an effective therapy in advanced gastric cancer , 2002, Anti-cancer drugs.

[15]  M. Fukushima,et al.  Dihydropyrimidine dehydrogenase activity and mRNA expression in advanced gastric cancer analyzed in relation to effectiveness of preoperative 5-fluorouracil-based chemotherapy. , 2000, International journal of oncology.

[16]  T. Kobayashi,et al.  [Long-term outcome of preoperative chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR) for gastric cancer]. , 2000, Gan to kagaku ryoho. Cancer & chemotherapy.

[17]  H. Zhang,et al.  A favorable impact of preoperative FPLC chemotherapy on patients with gastric cardia cancer. , 2000, Oncology reports.

[18]  D. Morita,et al.  Evaluation of the new American Joint Committee on Cancer/International Union Against Cancer classification of lymph node metastasis from gastric carcinoma in comparison with the Japanese classification , 1999, Cancer.

[19]  J. Byles,et al.  Effects of parenteral nutrition support and chemotherapy on the phasic composition of tumor cells in gastrointestinal cancer. , 1999, JPEN. Journal of parenteral and enteral nutrition.

[20]  G. Sgourakis,et al.  Upper abdominal stop-flow perfusion as a neo and adjuvant hypoxic regional chemotherapy for resectable gastric carcinoma. A prospective randomized clinical trial. , 1999, Hepato-gastroenterology.

[21]  J. Hermans,et al.  Chemotherapy for operable gastric cancer: results of the Dutch randomised FAMTX trial. The Dutch Gastric Cancer Group (DGCG). , 1999, European journal of cancer.

[22]  P. Hermanek,et al.  Classification of regional lymph node metastasis from gastric carcinoma , 1998, Cancer.

[23]  F. Liu,et al.  [Influence of preoperative on gastric cancer tissues and cells]. , 1997, Zhonghua wai ke za zhi [Chinese journal of surgery].

[24]  H. Saito,et al.  [Significance of 5'-deoxy-5-fluorouridine (5'-DFUR) administration before surgery for advanced gastric and colonic cancers--activity of pyrimidine nucleoside phosphorylase (PyNPase) and serum immunosuppressive acidic protein (IAP)]. , 1996, Gan to kagaku ryoho. Cancer & chemotherapy.

[25]  A. Yamaguchi,et al.  [Study on the combined preoperative treatment with CDDP and HCFU for gastric cancer]. , 1996, Gan to kagaku ryoho. Cancer & chemotherapy.

[26]  P. Fayers,et al.  Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial , 1996, The Lancet.

[27]  N. Tanaka,et al.  胃癌に対するBiological response modifiers (BRM)の術前腫瘍内注射療法 , 1995 .

[28]  J. Hermans,et al.  Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients , 1995, The Lancet.

[29]  S. Onodera,et al.  [Evaluation of medicinal lymph node dissection in advanced gastric cancer]. , 1994, Nihon Geka Gakkai zasshi.

[30]  M. Zembala,et al.  Preoperative endoscopic intratumor application of tumor necrosis factor alpha in patients with locally advanced resectable gastric cancer. , 1994, Endoscopy.

[31]  J. Chmiel,et al.  Cancer of the stomach. A patient care study by the American College of Surgeons. , 1993, Annals of surgery.

[32]  K. Kinoshita,et al.  Neoadjuvant chemotherapy for high-grade advanced gastric cancer , 1993, World Journal of Surgery.

[33]  R. Kanamaru,et al.  Histopathological evaluation on the effect of induced hypertension chemotherapy presurgically performed in patients with advanced carcinoma of the stomach. , 1992, The Tohoku journal of experimental medicine.

[34]  M. Toi,et al.  Prospective randomized controlled study on bestatin in resectable gastric cancer —Third report— , 1990, The Japanese journal of surgery.

[35]  A. Oshima,et al.  A long‐term follow‐up study of patients with gastric cancer detected by mass screening , 1989, Cancer.

[36]  Jin Pok Kim The concept of immunochemosurgery in gastric cancer , 1987, World journal of surgery.

[37]  M. Miyazaki,et al.  A study of survival in patients with stomach cancer treated by a combination of preoperative intra‐arterial infusion therapy and surgery , 1976, Cancer.

[38]  Yasushi Watanabe,et al.  Studies on preoperative cancer chemotherapy. Methods of preoperative intra‐arterial infusion by the use of methotrexate or vinblastine , 1969, Cancer.

[39]  Hirofumi Suzuki A Histological and Cytological Effect of Preoperative Chemotherapy for Advanced Gastric Cancer. Evaluation of the Combination Chemotherapy with 5FU and Low Dose CDDP. , 1999 .

[40]  J. Siewert,et al.  [The German EORTC Study of neoadjuvant therapy of stomach carcinoma]. , 1998, Langenbecks Archiv fur Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft fur Chirurgie. Kongress.

[41]  Z. Puchalski,et al.  The prospective multicenter trial of gastric cancer. , 1998, Langenbecks Archiv fur Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft fur Chirurgie. Kongress.

[42]  P. Wingo,et al.  Cancer statistics, 1997 , 1997, CA: a cancer journal for clinicians.

[43]  N. Kaibara,et al.  Enhanced induction of apoptosis of human gastric carcinoma cells after preoperative treatment with 5‐fluorouracil , 1997, Cancer.

[44]  P. Wingo,et al.  Cancer statistics, 1996 , 1996, CA: a cancer journal for clinicians.

[45]  T. Hattori,et al.  Prospective randomized controlled study on bestatin in resectable gastric cancer. , 1991, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[46]  C. McConkey,et al.  Cancer of the stomach. , 1989 .

[47]  Josef Korinek,et al.  Proceedings of the American Society of Clinical Oncology , 1982 .