Abstract
Purpose
We analyzed the natural history of advanced gastric cancer with sequential salvage chemotherapy following first-line treatment.
Methods
We studied 532 patients with unresectable gastric adenocarcinoma who were treated at Yonsei Cancer Center (2000–2008). The patients were managed with multiple sequential salvage chemotherapy as allowed by performance status and toxicity profiles. The tumor response was assessed every two cycles.
Results
Four hundred sixty patients received palliative chemotherapy and 72 received supportive care only. The median overall survival was 12.0 months for all patients, 12.1 months for the chemotherapy group, and 2.5 months for the supportive care group (P < 0.001). In the chemotherapy group, 87% received first-line chemotherapy, 47% second-line, 23% third-line, 9% fourth-line, and 3% fifth-line. Response rates were 24.8, 12.6, 10.9, 2.6, and 0% and disease control rates were 76.3, 60.1, 54.2, 54.2, and 53.3% for first- to fifth-line treatment, respectively. The median progression-free survival was 5.5, 3.4, 2.5, 1.9, and 2.0 months and overall survival was 12.1, 7.9, 5.5, 5.0, and 6.8 months. Performance status and metastatic pattern were consistent prognostic factors throughout salvage treatment.
Conclusions
Clinical trials may be feasible in second- or third-line salvage chemotherapy for gastric cancer. Future clinical trials in these settings should take into account the low response rate, short progression-free survival, and the prognostic factors for optimal trial design.
Similar content being viewed by others
References
Parkin DM, Pisani P, Ferlay J (1999) Global cancer statistics. CA Cancer J Clin 49:33–64
Shin HR, Jung KW, Won YJ, Park JG, KCCR-affiliated Hospitals (2004) 2002 Annual report of the Korea central cancer registry: based on registered data from 139 hospitals. Cancer Res Treat 36:103–114
D’Angelica M, Gonen M, Brennan MF, Turnbull AD, Bains M, Karpeh MS (2004) Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg 240:808–816
Kim S, Lim DH, 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
Glimelius B, Ekström K, Hoffman K, Graf W, Sjödén PO, Haglund U, Svensson C, Enander LK, Linné T, Sellström H, Heuman R (1997) Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol 8:163–168
Pyrhönen S, Kuitunen T, Nyandoto P, Kouri M (1995) Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 71:587–591
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 (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
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 20:666–673
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358:36–46
Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9:215–221
de Marinis F, Grossi F (2008) Clinical evidence for second- and third-line treatment options in advanced non-small cell lung cancer. Oncologist 13(Suppl 1):14–20
Grothey A, Sargent D (2005) Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used first line. J Clin Oncol 23:9441–9442
Dean-Colomb W, Esteva FJ (2008) Emerging agents in the treatment of anthracycline- and taxane-refractory metastatic breast cancer. Semin Oncol 35(2 Suppl 2):S31–S38 (quiz S40)
Zhong H, Zhang Y, Ma S, Ying JE, Yang Y, Yong D, Hang X, Sun Q, Zhong B, Wang D (2008) Docetaxel plus oxaliplatin (DOCOX) as a second-line treatment after failure of fluoropyrimidine and platinum in Chinese patients with advanced gastric cancer. Anticancer Drugs 19:1013–1018
Jeong J, Jeung HC, Rha SY, Im CK, Shin SJ, Ahn JB, Noh SH, Roh JK, Chung HC (2008) Phase II study of combination chemotherapy of 5-fluorouracil, low-dose leucovorin, and oxaliplatin (FLOX regimen) in pretreated advanced gastric cancer. Ann Oncol 19:1135–1140
Kim ST, Kang WK, Kang JH, Park KW, Lee J, Lee SH, Park JO, Kim K, Kim WS, Jung CW, Park YS, Im YH, Park K (2005) Salvage chemotherapy with irinotecan, 5-fluorouracil and leucovorin for taxane- and cisplatin-refractory, metastatic gastric cancer. Br J Cancer 92:1850–1854
Jo JC, Lee JL, Ryu MH, Sym SJ, Lee SS, Chang HM, Kim TW, Lee JS, Kang YK (2007) Docetaxel monotherapy as a second-line treatment after failure of fluoropyrimidine and platinum in advanced gastric cancer: experience of 154 patients with prognostic factor analysis. Jpn J Clin Oncol 37:936–941
Park SH, Choi EY, Bang SM, Cho EK, Lee JH, Shin DB, Ki Lee W, Chung M (2005) Salvage chemotherapy with irinotecan and cisplatin in patients with metastatic gastric cancer failing both 5-fluorouracil and taxanes. Anticancer Drugs 16:621–625
Graziano F, Catalano V, Baldelli AM, Giordani P, Testa E, Lai V, Catalano G, Battelli N, Cascinu S (2000) A phase II study of weekly docetaxel as salvage chemotherapy for advanced gastric cancer. Ann Oncol 11:1263–1266
Vanhoefer U, Wilke H, Weh HJ, Clemens M, Harstrick A, Stahl M, Hossfeld DK, Seeber S (1994) Weekly high-dose 5-fluorouracil and folinic acid as salvage treatment in advanced gastric cancer. Ann Oncol 5:850–851
Schmid KE, Kornek GV, Schüll B, Raderer M, Lenauer A, Depisch D, Lang F, Scheithauer W (2003) Second-line treatment of advanced gastric cancer with oxaliplatin plus raltitrexed. Onkologie 26:255–258
Maekawa K, Saeki M, Saito Y, Ozawa S, Kurose K, Kaniwa N, Kawamoto M, Kamatani N, Kato K, Hamaguchi T, Yamada Y, Shirao K, Shimada Y, Muto M, Doi T, Ohtsu A, Yoshida T, Matsumura Y, Saijo N, Sawada J (2007) Genetic variations and haplotype structures of the DPYD gene encoding dihydropyrimidine dehydrogenase in Japanese and their ethnic differences. J Hum Genet 52:804–819
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 92:205–216
Chau I, Norman AR, Ross PJ, Waters JS, Oates J, Cunningham D (2004) Multivariate prognostic factor analysis and second-line treatment in locally advanced and metastatic oesophago-gastric cancer—pooled analysis of 1080 patients from three multicentre randomised controlled trials using individual patient data. ASCO Gastrointestinal Cancers Symposium. Abstract 5
Lee J, Lim T, Uhm JE, Park KW, Park SH, Lee SC, Park JO, Park YS, Lim HY, Sohn TS, Noh JH, Heo JS, Park CK, Kim S, Kang WK (2007) Prognostic model to predict survival following first-line chemotherapy in patients with metastatic gastric adenocarcinoma. Ann Oncol 18:886–891
Thuss-Patience PC, Kretzschmar A, Deist T, Hinke A, Bichev D, Lebedinzew B, Schumacher G, Gebauer B, Maier V, Reichardt P (2009) Irinotecan versus best supportive care (BSC) as second-line therapy in gastric cancer: a randomized phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). J Clin Oncol 27(15S): abstract 4540
Cutsem EV, Kang Y, Chung H, Shen L, Sawaki A, Lordick F, Hill J, Lehle M, Feyereislova A, Bang Y (2009) Efficacy results from the ToGA trial: a phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). J Clin Oncol 27(18S):LBA4509
Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R (2008) 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 19:1450–1457
Ichikawa W, Sasaki Y (2006) Correlation between tumor response to first-line chemotherapy and prognosis in advanced gastric cancer patients. Ann Oncol 17:1665–1672
Kornek GV, Raderer M, Schüll B, Fiebiger W, Gedlicka C, Lenauer A, Depisch D, Schneeweiss B, Lang F, Scheithauer W (2002) Effective combination chemotherapy with paclitaxel and cisplatin with or without human granulocyte colony-stimulating factor and/or erythropoietin in patients with advanced gastric cancer. Br J Cancer 86:1858–1863
Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE (2006) Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24:2903–2909
Catalano V, Graziano F, Santini D, D’Emidio S, Baldelli AM, Rossi D, Vincenzi B, Giordani P, Alessandroni P, Testa E, Tonini G, Catalano G (2008) Second-line chemotherapy for patients with advanced gastric cancer: who may benefit? Br J Cancer 99:1402–1407
Acknowledgments
Supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MOST) (R11-2000-082-03002-0, R11-2000-082-03006-0, R11-2000-082-02008-0).
Conflict of interest statement
There are no conflicts of interest for any listed authors.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Moon, Y.W., Rha, S.Y., Jeung, HC. et al. Outcomes of multiple salvage chemotherapy for advanced gastric cancer: implications for clinical practice and trial design. Cancer Chemother Pharmacol 66, 797–805 (2010). https://doi.org/10.1007/s00280-010-1295-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-010-1295-z