Abstract
Purpose
Feasibility and efficacy of four different adjuvant radiochemotherapy regimens in patients with completely resected gastric cancer were evaluated in consecutive cooperative phase II trials using different 5-fluorouracil (5-FU)-based combination chemotherapies (CTX) and 5-FU-enhanced radiotherapy.
Methods
Between 2000 and 2005, 157 patients with completely resected gastric adenocarcinoma were included. The study design was based on two cycles of CTX and irradiation with 45 Gy plus concomitant 5-FU 225 mg/m2 per 24 h between these two cycles. CTX cycles consisted of 5-FU, folinic acid (FA), cisplatin plus paclitaxel (FLPP); 5-FU, FA and cisplatin (FLP); 5-FU, FA and irinotecan (FLI); or 5-FU, cisplatin plus docetaxel (FPD).
Results
Median follow-up for all four trials was 18 months (range, 1–64) without significant difference between the four regimens: FLPP 30 months (2–46+), FLP 18 months (1–64+), FLI 15 months (1–26), FPD 10 months (5–19+). Treatment associated toxicity was tolerable and did not differ significantly between the four CTX regimens. Across all patients grade ¾, toxicities during the first cycle/chemoradiation/second cycle consisted of leukocytopenia 4%/2%/30%, anorexia 5%/10%/6%, diarrhea 6%/1%/3%, nausea 2%/7%/2%. Early death occurred in one patient due to Pneumocystis carinii pneumonia. Median progression free survival was 23 months for FLPP, 18 months for FLP, 14 months for FLI, 9 months for FPD (not significant). One-year-overall survival rates were 95% for FLPP, 82% for FLP, 94% for FLI, 86% for FPD.
Conclusion
Adjuvant radiochemotherapy in patients with gastric cancer can be safely given continuous infusion of 5-FU at 225 mg/m2 per day. In addition, a variety of 5-FU-based multiagent chemotherapy regimen with defined activity in gastric cancer appears both safe and effective when given prior and after radiochemotherapy in this setting.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bajetta E, Buzzoni R, Mariani L, Beretta E, Bozzetti F, Bordogna G et al (2002) Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian Trials in Medical Oncology (ITMO) Group. Ann Oncol 13:299–307. doi:10.1093/annonc/mdf040
Bouche O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Federation Francophone de Cancerologie Digestive Group et al (2004) Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study–FFCD 9803. J Clin Oncol 22:4319–4328. doi:10.1200/JCO.2004.01.140
Bouche O, Ychou M, Burtin P, Bedenne L, Ducreux M, Lebreton G, Federation Francophone de Cancerologie Digestive Group et al (2005) Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Ann Oncol 16:1488–1497. doi:10.1093/annonc/mdi270
Cascinu S, Labianca R, Barone C, Santoro A, Carnaghi C, Cassano A, Beretta GD, Catalano V, Bertetto O, Barni S, Frontini L, Aitini E, Rota S, Torri V, Floriani I, Italian Group for the Study of digestive Tract Cancer, Pozzo C, Rimassa L, Mosconi S, Giordani P, Ardizzoia A, Foa P, Rabbi C, Chiara S, Gasparini G, Nardi M, Mansutti M, Arnoldi E, Piazza E, Cortesi E, Pucci F, Silva RR, Sobrero A, Ravaioli A (2007) Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. J Natl Cancer Inst 18:601–607. doi:10.1093/jnci/djk131
Coburn NG, Swallow CJ, Kiss A, Law C (2006) Use of lymph node ratio improves staging and selection criteria for adjuvant therapy of gastric cancer. J Clin Oncol 24(18S):4051
De Vita F, Giuliani F, Orditura M, Maiello E, Galizia G, Di Martino N, Montemurro F, Cartenì G, Manzione L, Romito S, Gebbia V, Ciardiello F, Catalano G, Colucci G, Gruppo Oncologico Italia Meridionale (2007) Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study). Ann Oncol 18:1354–1358. doi:10.1093/annonc/mdm128
Earle CC, Maroun JA (1999) Adjuvant chemotherapy after curative resection for gastric cancer in non-Asian patients: revisiting a meta-analysis of randomised trials. Eur J Cancer 35:1059–1064. doi:10.1016/S0959-8049(99)00076-3
Gunderson LL (2002) Gastric cancer—patterns of relapse after surgical resection. Semin Radiat Oncol 12:150–161. doi:10.1053/srao.2002.30817
Hallisey MT, Dunn JA, Ward LC, Allum WH (1994) The second British Stomach Cancer Group trial of adjuvant radiotherapy in resectable gastric cancer: five-year follow-up. Lancet 343:1309–1312. doi:10.1016/S0140-6736(94)92464-3
Hartgrink HH, Van de Velde CJ, Putter H, Bonenkamp JJ, Klein Kranenberg E, Songun I et al (2004) Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial. J Clin Oncol 22:2069–2077. doi:10.1200/JCO.2004.08.026
Hermanns J, Bonenkamp JJ, Boon MC, Bunt AM, Ohyama S, Sasako M et al (1993) Adjuvant therapy after curative resection for gastric cancer: meta-analysis of randomized trials. J Clin Oncol 11:1441–1447
Honecker F, Kollmannsberger C, Quietsch D, Haag C, Schroeder M, Spott C et al (2002) Phase II study of weekly paclitaxel plus 24-h continuous infusion 5-fluorouracil, folinic acid and 3-weekly cisplatin for the treatment of patients with advanced gastric cancer. Anticancer Drugs 13:497–503. doi:10.1097/00001813-200206000-00008
Hu JK, Chen ZX, Zhou ZG, Zhang B, Tian J, Chen JP et al (2002) Intravenous chemotherapy for resected gastric cancer: meta-analysis of randomized controlled trials. World J Gastroenterol 8:1023–1028
Janunger KG, Hafstrom L, Glimelius B (2002) Chemotherapy in gastric cancer: a review and updated meta-analysis. Eur J Surg 168:597–608. doi:10.1080/11024150201680005
Kaplan E, Meier P (1958) Nonparametric estimation from incomplete observations. Am J Stat Assoc 53:457–481. doi:10.2307/2281868
Kim S, Lim-do H, Lee J, Kang WK, MacDonald JS, Park CH, Park SH, Lee SH, Kim K, Park JO, Kim WS, Jung CW, Park YS, Im YH, Sohn TS, Noh JH, Heo JS, Kim YI, Park CK, Park K (2005) An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach. Int J Radiat Oncol Biol Phys 63:1279–1285. doi:10.1016/j.ijrobp.2005.05.005
Kollmannsberger C, Quietzsch D, Haag C, Lingenfelser T, Schroeder M, Hartmann JT et al (2000) A phase II study of paclitaxel, weekly, 24-hour continous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer. Br J Cancer 83:458–462. doi:10.1054/bjoc.2000.1295
Kollmannsberger C, Budach W, Stahl M, Schleucher N, Hehr T, Wilke H et al (2005) Adjuvant chemoradiation using 5-fluorouracil/folinic acid/cisplatin with or without paclitaxel and radiation in patients with completely resected high-risk gastric cancer: two cooperative phase II studies of the AIO/ARO/ACO. Ann Oncol 16:1326–1333. doi:10.1093/annonc/mdi252
Lee HS, Choi Y, Hur WJ, Kim HJ, Kwon HC, Kim SH et al (2006) Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine. World J Gastroenterol 12:603–607
Leong T, Michael M, Foo K, Thompson A, Lim Joon D, Weih L et al (2003) Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation. Br J Cancer 89:1433–1438. doi:10.1038/sj.bjc.6601311
Lutz MP, Wilke H, Wagener DJ, Vanhoefer U, Jeziorski K, Hegewisch-Becker S, Balleisen L, Joossens E, Jansen RL, Debois M, Bethe U, Praet M, Wils J, Van Cutsem E, European Organisation for Research and Treatment of Cancer Gastrointestinal Group Arbeitsgemeinschaft Internistische Onkologie (2007) Weekly infusional high-dose fluorouracil (HD-FU), HD-FU plus folinic acid (HD-FU/FA), or HD-FU/FA plus biweekly cisplatin in advanced gastric cancer: randomized phase II trial 40953 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group and the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol 25:2580–2585. doi:10.1200/JCO.2007.11.1666
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN et al (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345:725–730. doi:10.1056/NEJMoa010187
Mari E, Florianui I, Tinazzi A, Buda A, Belfiglio M, Valentini M et al (2000) Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis of published randomised trials. A study of the GISCAD (Gruppo Italiano per lo Studio dei Carcinomi dell’Apparato Digerente). Ann Oncol 11:837–843. doi:10.1023/A:1008377101672
Nitti D, Wils J, Guimares Dos Santos J, Fountzilas G, Conte PF, Sava C et al (2006) Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer. A combined analysis of the EORTC GI Group and the ICCG. Ann Oncol 17:262–269. doi:10.1093/annonc/mdj077
Panzini I, Gianni L, Fattori PP, Tassinari D, Imola M, Fabbri P et al (2002) Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and a comparison with previous meta-analyses. Tumori 88:21–27
Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P et al (2002) A prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) with epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20:1996–2004. doi:10.1200/JCO.2002.08.105
Scartozzi M, Galizia E, Graziano F, Catalano V, Berardi R, Baldelli AL, Testa E, Mari D, Silva RR, Cascinu S (2005) Over-DI dissection may question the value of radiotherapy as a part of an adjuvant programme in high-risk radically resected gastric cancer patients. Br J Cancer 92:1051–1054. doi:10.1038/sj.bjc.6602468
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, V325 Study Group (2006) 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 24:4991–4997. doi:10.1200/JCO.2006.06.8429
Welz S, Hehr T, Kollmannsberger C, Bokemeyer C, Belka C, Budach W (2007) Renal toxicity of adjuvant chemoradiotherapy with cisplatin in gastric cancer. Int J Radiat Oncol Biol Phys 69(5):1429–1435
Zhang ZX, Gu XZ, Yin WB, Huang GJ, Zhang DW, Zhang RG (1998) Randomized clinical trial on the combination of the preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (ACG)-report on 370 patients. In J Radiat Oncol Biol Phys 42:929–934
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Oechsle, K., Bokemeyer, C., Hartmann, J.T. et al. Four consecutive multicenter phase II trials of adjuvant chemoradiation in patients with completely resected high-risk gastric cancer: the experience of the German AIO/ARO/CAO group. J Cancer Res Clin Oncol 135, 163–172 (2009). https://doi.org/10.1007/s00432-008-0463-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-008-0463-6