Abstract
Stomach cancer is still one of the most prevalent malignancies and is the main cause of cancer deaths worldwide. The outcome for patients with metastasis, as well as for those with tumor recurrence, is dismal, with median survival time not greater than a year. Patients with unresectable locally advanced or metastatic lesions have been treated with systemic chemotherapy, and several randomized studies have demonstrated the benefit of chemotherapy compared with best supportive care. Recently, randomized phase III trials have presented a benefit of second-line chemotherapy compared with supportive care alone. However, it is not known at present which drug is the most effective in this setting. In Korea, the practice of offering second-line treatment to patients with advanced gastric cancer (AGC) is common, and many prospective clinical trials investigating clinical outcomes of second-line chemotherapy have been reported. Therefore, to define the potential role of second-line chemotherapy and to help to select an effective regimen, we review the published Korean prospective data concerning the use of chemotherapy in the second-line setting for the treatment of AGC. No phase III trials but 20 phase II trials were identified. The benefit of second-line chemotherapy in AGC has indirect evidence considering prolongation of progression-free survival (PFS) and improvement of the response rate. Taxanes, irinotecan, and oxaliplatin have been studied much and might be promising drugs considering cross-resistance to a 5-fluorouracil and cisplatin combination (FP). A large, prospective, multicenter, randomized phase III study is warranted to select the most effective second-line chemotherapeutic agents.
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Introduction
Although the incidence of advanced gastric cancer (AGC) is decreasing in many countries, AGC is still one of the most prevalent malignancies in many countries, including Korea [1, 2]. Recently, improvements in early diagnosis have increased the number of patients who are able to undergo curative resection. However, 70% of patients with gastric cancer are considered incurable at the time of diagnosis due to their advanced disease. The relapse rate is high, at 4065%, for patients who undergo a curative (R0) resection [3]. The prognosis for patients with metastatic disease is very poor, with 5-year survival being less than 5% [4].
For AGC, 5-fluorouracil (5-FU)-based chemotherapy resulted in a survival benefit compared to best supportive care (BSC) in the 1990s [5–7]. Subsequently, three randomized trials that used 5-FU alone as the reference arm and compared it with older-generation 5-FU-based combination regimens have been reported [8–10]. In Korea, Kim et al. reported that a combination of 5-FU and cisplatin (FP) showed a significantly higher patient response rate (RR) and a longer time to progression (TTP) than a combination of 5-FU, doxorubicin, and mitomycin C (FAM) or the fluorouracil regimen [9], and FP is now standard palliative first-line chemotherapy in Korea.
Patients with AGC have been treated with systemic chemotherapy, and several randomized studies have shown a modest improvement in the quality of life (QOL) and survival benefit of chemotherapy compared with BSC [6, 7, 11]. However, when patients receiving chemotherapy eventually develop progressive disease, no established second-line regimen can be offered, despite this being a common clinical scenario. Nevertheless, most patients in Korea are candidates for second-line therapy after failing to respond to first-line therapy because advanced or recurrent gastric cancer such as hematogenous/lymphatic metastasis or peritoneal seeding is very progressive. Additionally, patients with good performance status (PS) want second-line chemotherapy. Therefore, many studies have investigated second-line chemotherapy regimens for advanced gastric adenocarcinoma in Korea. However, there have been no review articles concerning second-line chemotherapy in which the first-line chemotherapy of AGC has been considered. We reviewed reports of clinical trials conducted in Korea, where FP has been standard palliative first-line chemotherapy.
The purpose of this review was to evaluate the efficacy and tolerability of second-line chemotherapy for unresectable or recurrent gastric cancers. In particular, we focused on RR, overall survival (OS), and tolerability. We then reviewed options for the second-line treatment of AGC on the basis of available evidence in Korea.
Materials and methods
We conducted a PubMed database electronic literature search up to December 2010 for phase II/III trials in Korea published in full and in literature reviews. Criteria for inclusion of references were that patients had histologically proven recurrent or primarily unresectable gastric adenocarcinomas and had been previously treated with single regimens of palliative chemotherapy, with response assessed by WHO or RECIST criteria. Articles concerning immunotherapy or other non-cytotoxic agents or assessing the response of several different tumor types to the same drug regimen were not included. Trials including chemo-naïve patients were excluded. However, studies of salvage chemotherapy were included, but only if the number of patients receiving second-line chemotherapy was more than ten. No language restrictions were used.
Most trials of second-line AGC chemotherapy have been performed in Japan, Korea, and Italy, where the practice of offering second-line treatment to patients with AGC is common [12]. The first-line chemotherapies used in these countries are different. No review article concerning second-line chemotherapy considered what the first-line chemotherapy of AGC was. We selected reports of clinical trials conducted in Korea.
Results
We identified 20 phase II trials including patients with histologically proven gastric adenocarcinoma who had received one previous palliative chemotherapy regimen. No phase III trials were identified. A total of 696 patients with locally advanced and/or metastatic gastric cancer were evaluated for the response and toxicity of second-line chemotherapy according to WHO or RECIST criteria. None of the trials included patients with esophageal adenocarcinoma.
Taxanes, irinotecan, oral 5-FU agents such as capecitabine or S-1, platinum agents (cisplatin, carboplatin, or oxaliplatin), epirubicin, and mitomycin C were tested as second-line regimens. Despite paclitaxel, docetaxel, irinotecan, and S-1 being used as single agents [13–16], most studies tried combination regimens. Taxanes were commonly used in one of the second-line combination regimens, followed by irinotecan, a platinum agent, and 5-FU agents, including S-1 and capecitabine.
Taxanes
Taxanes bind and stabilize microtubules, which leads to cell-cycle arrest, and these agents have been used in the first-line setting for AGC. Of 9 studies that reported the role of taxanes in second-line chemotherapy, 4 investigated paclitaxel and 5 examined docetaxel (Table 1). Paclitaxel was used as a single agent or combined with a platinum agent (cisplatin or carboplatin). Paclitaxel alone was used as a split dose for patients with poor PS [17]. Weekly paclitaxel was used at 70 mg/m2 in heavily pretreated patients. The efficacy as second-line chemotherapy was shown by an RR of 4% and OS of 5.1 months. Grade 3 or 4 leukopenia was found in 23% of patients [18]. Chang et al. reported the efficacy and safety of paclitaxel 200 mg/m2 plus carboplatin 6 AUC in AGC patients previously treated with FP. The RR of this regimen was 22% with a median progression-free survival (PFS) of 14 weeks and a median OS of 32 weeks. However, grade 3 or 4 neutropenia developed in 40% of patients, and dose modification was suggested. The most common non-hematological toxicities were neuropathy and arthralgia [19]. Combinations of paclitaxel and cisplatin have also been studied. Lee et al. used paclitaxel 145 mg/m2 plus cisplatin 60 mg/m2 in patients pretreated with FP. The RR in this study was 28% with a median OS of 9.1 months. Grade 3 or more neutropenia occurred in 9% of patients [20]. A higher-dose regimen of paclitaxel 175 mg/m2 plus cisplatin 70 mg/m2 every 3 weeks showed an RR of 10% and a median OS of 7.5 months in AGC patients pretreated with 5-FU. The most common complication was neutropenia, with grade 3or 4 neutropenia being observed in 26% of patients [21].
Docetaxel was also used for AGC as a single agent or combined with various other drugs [22]. Docetaxel 75 mg/m2 given every 3 weeks produced an overall RR of 16% and a median OS of 8.3 months in patients who failed first-line treatments with the FP regimen [15]; 18% of the patients developed grade 3 or 4 neutropenia. The percentages of patients with non-hematological toxicities of grade 3 or worse were as follows: asthenia (33%), diarrhea (10%), and peripheral sensory neuropathy (8%). Kim et al. gave docetaxel 75 mg/m2 and cisplatin 60 mg/m2 every 3 weeks and showed that the RR was 32% with a median OS of 7.8 months. The most common grade 3 or 4 toxicity of this regimen was neutropenia, at 51%, followed by leucopenia (27%), and oral mucositis (14%) [23]. In another similar study, by Park et al., docetaxel 60 mg/m2 and cisplatin 60 mg/m2 given every 3 weeks to AGC patients who had failed a 5-FU regimen produced an overall RR of 17% with a median OS of 5.8 months. The most common grade 3 or 4 toxicity was neutropenia (12%), followed by nausea/vomiting (5%) [24].
Higher doses of docetaxel (65 mg/m2) and irinotecan 160 mg/m2 and lower doses of docetaxel (50 mg/m2) and irinotecan (120 mg/m2) in patients with relapsed or progressive AGC after prior fluoropyrimidine or platinum-based chemotherapy produced overall RRs of 20.3 and 10.3%, respectively, but the incidences of grade 3 or 4 neutropenia were higher, at 90 and 71%, respectively [25]. Lim et al. conducted a study to assess the efficacy and tolerability of docetaxel and epirubicin in advanced or metastatic gastric cancer patients with progression after FP chemotherapy [18]. This study reported an overall RR of 22% with a median OS of 13.4 months. The most common grade 3 or 4 toxicity was neutropenia (47%).
Irinotecan
Irinotecan is a semi-synthetic water-soluble derivative of the plant alkaloid camptothecin. It is enzymatically converted to its active metabolite, SN-38, which inhibits the eukaryotic enzyme DNA-topoisomerase I, thus blocking cells in the S-phase of the cell cycle [26]. Irinotecan was used as a single agent or combined with cisplatin, docetaxel, or 5-FU/id LV combiantion (FL) (Table 2). Single-agent irinotecan 125 mg/m2 weekly for 4 weeks followed by 2 weeks’ rest achieved an RR of 20% with a median OS of 5.2 months in AGC patients who had failed cisplatin-based chemotherapy [13]. Grade 3 or 4 neutropenia developed in 67.6% of patients while on the study medication, and 16.2% of patients developed febrile neutropenia. Grade 3 or worse nonhematological toxicities were diarrhea (18.9%) and nausea/vomiting (18.9%).
Irinotecan was combined with FL (FOLFIRI); the RR was 21% with a median OS of 7.6 months. The incidence of grade 3 or 4 neutropenia was 1117.6% [27–29]. Irinotecan was also combined with cisplatin [30, 31]; the RR was 15.625% with a median OS of 5.66.1 months. Neurotoxicity developed in 43% of patients, and grade 3 or 4 neutropenia occurred in 1118.8% of patients.
Platinum agents
Platinum agents were commonly used in combination regimens, such as 5-FU or paclitaxel for first-line chemotherapy. However, many studies reused cisplatin or oxaliplatin as part of a combination regimen for patients who had previously received a cisplatin combination regimen and failed it. Cisplatin was combined with a taxane (TP/DP) [20, 21, 23, 24] and with irinotecan (IrP) [30, 31]; carboplatin was combined with paclitaxel (TC) [19], and oxaliplatin was combined with FL (FOLFOX) [32, 33]. The RR of FOLFOX varied according to the dosage of oxaliplatin and FL, at 526% with a median OS of 6.67.3 months (Table 3). In the studies using the FOLFOX regimen more than half of the patients had an Eastern Cooperative Oncology Group (ECOG) PS of 2.
New oral fluorouracil/fluoropyrimidine agents
S-1 is an oral fluoropyrimidine in which tegafur has been combined with gimeracil and potassium oxonate. Capecitabine is a fluoropyrimidine carbamate, which is converted to 5-fluorouracil selectively in tumors through the intermediate metabolite 5’-deoxy-5-fluorouridine.
Table 4 lists the studies concerning oral fluorouracil/fluoropyrimidine agents. Shin et al. assessed the activity and safety profile of a combination of capecitabine and doxorubicin, which was used as second-line therapy to treat 26 patients and showed an RR of 6.7% and a median OS of 29.1 weeks [34]. Single-agent S-1 in the second-line setting produced an overall RR of 9.4% with a median OS of 10.4 months [16]. An S-1 plus mitomycin combination as second-line therapy showed a 21% overall RR with a median OS of 8.0 months [35].
Discussion
Systemic chemotherapy in AGC leads to improvement in survival and attenuation of symptoms compared with BSC alone [6, 7]. The choice of a second-line agent depends on the first-line treatment, which is slightly different in different countries. Three randomized trials using 5-FU showed that no combination regimen demonstrated a survival benefit compared with 5-FU alone; however, better RR and PFS were observed [8–10]. The interpretation of these results, particularly for determining the reference arms, differed among regions. In Japan, 5-FU alone was selected as the reference arm, because no differences in OS were observed. Although no OS benefit was demonstrated, the FP regimen, which showed a high RR and prolonged PFS, has been the backbone of chemotherapy in Korea [9]. In most European countries, a three-drug regimen, of epirubicin, cisplatin, and 5-FU (ECF) is more commonly used, based on a phase III randomized trial comparing ECF with 5-FU, doxorubicin, and methotrexate (FAMTX) [36].
In Korea, it has been common practice that patients failing first-line palliative chemotherapy receive second-line chemotherapy; in this country it is possible to detect AGC in patients with good performance because gastroscopy has been easily accessible and has been used as one of the primary screening methods for more than 40 years. According to retrospective data, 50% of patients in Korea failing first-line chemotherapy received second-line chemotherapy [37].
The survival benefit of second-line treatment
From the results of Japanese studies, the OS of second-line treatment was reported to be around 12 months, which is obviously longer than the OS of around 8 months in Western countries [10, 38, 39]. These favorable survival outcomes presumably resulted not only from differences in eligibility criteria and baseline patient characteristics such as measurable metastatic disease and ethnic differences, but also differences between the trials in the proportions of patient populations who received second-line chemotherapy [39, 40]. According to a review of second-line chemotherapy for AGC, the activity of chemotherapy in the second-line treatment of AGC can be seen in terms of RR (438%), PFS (2.55.0 months), and OS (3.510.9 months) [12]. These results indirectly demonstrate the role of second-line chemotherapy in AGC. Moreover, active and tolerable salvage chemotherapy can improve QOL and clinical outcomes in a certain proportion of selected patients [41]. A multicenter, randomized phase III trial comparing second-line chemotherapy plus BSC with BSC alone for pretreated AGC has been presented in an abstract [42].
What is the optimum active agent for second-line chemotherapy
As second-line regimens, various drugs, such as taxanes, irinotecan, 5-FU agents including capecitabine and S-1, platinum agents (cisplatin, carboplatin, and oxaliplatin), adriamycin, epirubicin, and mitomycin C have been tested. The data on active second-line agents are not conclusive because most published studies include only a small number of patients and contain heterogeneous populations of patients who have locally advanced or metastatic cancers. Paclitaxel, docetaxel, and irinotecan were found to be promising drugs whether they were used in combination regimens or as single agents. Prospective, randomized phase III studies are needed to assess whether some drugs are better used as a single agent or in combination, and which drugs should be selected.
Cross-resistance to platinum agents and 5-fluorouracil
Most studies reviewed here used combination regimens as second-line chemotherapy. Platinum agents were most commonly used as part of the combination regimen. It is reasonable to consider a platinum agent for patients who have not been previously exposed to these agents. However, when cisplatin was reused as part of a combination regimen, it was not clear whether its inclusion improved the RR. Other components of platinum combination regimens in salvage therapies mainly consisted of taxanes and irinotecan, which have shown synergistic anti-tumor activity in combination with platinum in in vivo studies [43–45]. Cisplatin is a toxic drug causing multiple side effects, such as intractable nausea and vomiting, kidney and liver failure, and deafness, all of which may affect the QOL and PS of patients receiving second-line chemotherapy. Although carboplatin is known to have anti-tumor activity against gastric cancer cell lines and in animal models of gastric cancer [46], it has shown marginal activity in patients with stomach cancer, with RRs of 610% as a single agent [47, 48]. On the other hand, oxaliplatin has shown activity in many tumor cell lines resistant to cisplatin [49] and is expected to replace cisplatin in gastric cancer treatment. FOLFOX as second-line therapy in patients previously treated by FP showed modest activity.
5-FU has cytotoxic mechanisms that are different from those of taxanes, oxaliplatin, and irinotecan. It is not clear whether 5-FU or its prodrug combinations with these agents as second-line chemotherapy are more effective than single agents in view of the increased use of 5-FU and its prodrug in the first-line setting causing multiple side effects. Although it is difficult to compare studies using single agents or agents in combination with 5-FU, the RRs of single-agent paclitaxel and irinotecan were 4 and 19%, respectively [13, 14], and the RRs of combinations of these agents with 5-FU were 21 and 1021%, respectively [27–29, 50].
Combination chemotherapy or monotherapy
Although combination regimens might improve anti-tumor effects, they may also enhance toxicity and produce adverse events. In non-small cell lung cancer, single drugs such as docetaxel, pemetrexed, and TKI, a drug that has low toxicity and is tolerable, show survival benefit as second-line chemotherapy [51–53]. Taxanes, irinotecan, and TS-1 were given as single agents in second-line regimens.
Weekly paclitaxel in patients with poor PS is effective and well tolerated. In Japanese trials involving patients with a PS of 02, single-agent paclitaxel showed an RR of 1617.5% with OS of 7.88.5 months [54, 55]. Although paclitaxel doublet chemotherapy with fluoropyrimidines or platinum compounds produces modest improvements in tumor response and prognosis, such doublet therapy leads to more complications than single-agent paclitaxel therapy. To decrease toxicities, split-dose combination chemotherapy might be considered [56]. With regard to the schedule of paclitaxel administration, weekly injection also seemed to show less toxicity and better results than administration every 3 weeks [17]. Docetaxel is also an active drug in gastric cancer chemotherapy [22]. Docetaxel for patients having received a combination regimen of FP showed an RR of 16.7% with OS of 8.3 months, which is consistent with a previous report from Bang et al. [57] in 45 chemotherapy-naïve patients. The additive effect of cisplatin may be considered non-significant.
Weekly irinotecan as a single agent was modestly active against cisplatin-refractory gastric cancer in patients who had a good initial ECOG PS. Single-agent S-1 as a second-line drug was given to patients with paclitaxel- and cisplatin-refractory gastric cancer and showed active and safe outcomes. S-1 was also tolerable in AGC patients with poor PS. However, S-1 could be considered to be suitable for second-line treatment only in patients who have not received 5-FU-based first-line chemotherapy.
Of the combination regimens reviewed, in the studies using oxaliplatin-based regimens, and capecitabine/doxorubicin, more than half of the patients had a PS of 2 and the regimens showed modest efficacies. In addition, FOLFIRI or mitomycin plus S-1 might be active and tolerable regimens.
Target agents
Currently, trastuzumab in combination with chemotherapy has been approved as first-line chemotherapy for the treatment of Her2-positive AGC [58], but no target agents have been approved as second-line therapy. Bang and colleagues have reported that single-agent sunitinib has insufficient clinical value as a second-line treatment [59].
One substantial limitation of the present review is that the trials included were mostly phase II studies where the primary endpoint was not OS but TTP, PFS, or RR. Additionally, most studies included a small number of patients (<50). Another limitation is that most studies reviewed did not clearly mention the location of tumor in the inclusion criteria. In Korean studies, results for adenocarcinoma of the gastroesophageal junction (GEJ) should be separated from those for gastric adenocarcinoma considering there is an increasing trend of adenocarcinoma of the GEJ in both Western and Eastern countries [60, 61]. However, we note that the present study is the first systematic overview of second-line chemotherapy for gastric cancer in Korea, where FP has been adopted as a standard regimen and many trials of second-line therapy of AGC have been done.
In summary, the role of second-line chemotherapy in AGC has not yet been established by robust evidence through a large randomized phase III trial. However, considerable indirect evidence from numerous phase II studies strongly suggests prolongation of PFS and improved RR through the use of second-line chemotherapies. A combination regimen is preferred as the second-line treatment for gastric cancer, and platinum is still used as a part of the combination regimen. At the 2011 American Society of Clinical Oncology (ASCO) annual meeting, a large, prospective, multicenter, randomized phase III study to assess whether a benefit of second-line chemotherapy exists was reported. This trial compared active treatment (docetaxel or irinotecan) with BSC and reported a survival benefit of second-line chemotherapy [42]. Moreover, further studies might be designed to consider the regimens used during the whole treatment course, similar to the regimens used for colorectal cancer, for which the three drugs, 5-FU, irinotecan, and oxaliplatin, should all be used. In this sense, taxanes, irinotecan, and oxaliplatin are promising drugs considering cross-resistance of cisplatin or 5-FU. The Korean Cancer Study Group (KCSG) is initiating a new randomized, multicenter phase III trial to assess the efficacy of paclitaxel versus irinotecan in patients with recurrent or metastatic gastric cancer who progress following first-line therapy that excludes taxanes or irinotecan (http://clinicaltrial.gov, NCT01224652).
References
Hoel DG, Davis DL, Miller AB, Sondik EJ, Swerdlow AJ. Trends in cancer mortality in 15 industrialized countries, 1969–1986. J Natl Cancer Inst. 1992;84(5):313–20.
Shin HR, Ahn YO, Bae JM, Shin MH, Lee DH, Lee CW. Cancer incidence in Korea. Cancer Res Treat. 2002;34:405–8.
Cuschieri A, Weeden S, Fielding J, Bancewicz J, Craven J, Joypaul V, et al. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group. Br J Cancer. 1999;79(9-10):1522–30. PMCID: 2362742.
Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996. CA Cancer J Clin. 1996;46(1):5–27.
Glimelius B, Hoffman K, Haglund U, Nyren O, Sjoden PO. Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol. 1994;5(2):189–90.
Murad AM, Santiago FF, Petroianu A, Rocha PR, Rodrigues MA, Rausch M. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993;72(1):37–41.
Pyrhonen S, Kuitunen T, Nyandoto P, Kouri M. 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. 1995;71(3):587–91. PMCID: 2033628.
Cullinan SA, Moertel CG, Wieand HS, O’Connell MJ, Poon MA, Krook JE, et al. Controlled evaluation of three drug combination regimens versus fluorouracil alone for the therapy of advanced gastric cancer. North Central Cancer Treatment Group. J Clin Oncol. 1994;12(2):412–6.
Kim NK, Park YS, Heo DS, Suh C, Kim SY, Park KC, 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. 1993;71(12):3813–8.
Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, 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. 2003;21(1):54–9.
Glimelius B, Ekstrom K, Hoffman K, Graf W, Sjoden PO, Haglund U, et al. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol. 1997;8(2):163–8.
Wesolowski R, Lee C, Kim R. Is there a role for second-line chemotherapy in advanced gastric cancer? Lancet Oncol. 2009;10(9):903–12.
Chun JH, Kim HK, Lee JS, Choi JY, Lee HG, Yoon SM, et al. Weekly irinotecan in patients with metastatic gastric cancer failing cisplatin-based chemotherapy. Jpn J Clin Oncol. 2004;34(1):8–13.
Im CK, Rha SY, Jeung HC, Jeong J, Lee SH, Noh SH, et al. A phase II feasibility study of weekly paclitaxel in heavily pretreated advanced gastric cancer patients with poor performance status. Oncology. 2009;77(6):349–57.
Lee JL, Ryu MH, Chang HM, Kim TW, Yook JH, Oh ST, et al. A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy. Cancer Chemother Pharmacol. 2008;61(4):631–7.
Lee SJ, Cho SH, Yoon JY, Hwang JE, Bae WK, Shim HJ, et al. Phase II study of S-1 monotherapy in paclitaxel- and cisplatin-refractory gastric cancer. Cancer Chemother Pharmacol. 2009;65(1):159–66.
Sakamoto J, Matsui T, Kodera Y. Paclitaxel chemotherapy for the treatment of gastric cancer. Gastric Cancer. 2009;12(2):69–78.
Lim JY, Cho JY, Paik YH, Lee DK, Lee SI, Park HJ, et al. Salvage chemotherapy with docetaxel and epirubicin for advanced/metastatic gastric cancer. Oncology. 2007;73(1–2):2–8.
Chang HM, Kim TW, Ryu BY, Choi SJ, Park YH, Lee JS, et al. Phase II study of paclitaxel and carboplatin in advanced gastric cancer previously treated with 5-fluorouracil and platinum. Jpn J Clin Oncol. 2005;35(5):251–5.
Lee KW, Kim JH, Yun T, Song EK, Na II, Shin H, et al. Phase II study of low-dose paclitaxel and cisplatin as a second-line therapy after 5-fluorouracil/platinum chemotherapy in gastric cancer. J Korean Med Sci. 2007;22(Suppl):S115–21. PMCID: 2694374.
Shin SJ, Chun SH, Kim KO, Kim MK, Lee KH, Hyun MS, et al. The efficacy of paclitaxel and cisplatin combination chemotherapy for the treatment of metastatic or recurrent gastric cancer: a multicenter phase II study. Korean J Intern Med. 2005;20(2):135–40.
Nishiyama M, Wada S. Docetaxel: its role in current and future treatments for advanced gastric cancer. Gastric Cancer. 2009;12(3):132–41.
Kim H, Park JH, Bang SJ, Kim DH, Cho HR, Kim GY, et al. A phase II study of docetaxel and cisplatin in patients with gastric cancer recurring after or progressing during 5-FU/platinum treatment. Jpn J Clin Oncol. 2005;35(12):727–32.
Park SH, Kang WK, Lee HR, Park J, Lee KE, Lee SH, et al. Docetaxel plus cisplatin as second-line therapy in metastatic or recurrent advanced gastric cancer progressing on 5-fluorouracil-based regimen. Am J Clin Oncol. 2004;27(5):477–80.
Sym SJ, Chang HM, Kang HJ, Lee SS, Ryu MH, Lee JL, et al. A phase II study of irinotecan and docetaxel combination chemotherapy for patients with previously treated metastatic or recurrent advanced gastric cancer. Cancer Chemother Pharmacol. 2008;63(1):1–8.
Tanizawa A, Fujimori A, Fujimori Y, Pommier Y. Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. J Natl Cancer Inst. 1994;86(11):836–42.
Kim SG, Oh SY, Kwon HC, Lee S, Kim JH, Kim SH, et al. A phase II study of irinotecan with bi-weekly, low-dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFIRI) as salvage therapy for patients with advanced or metastatic gastric cancer. Jpn J Clin Oncol. 2007;37(10):744–9.
Kim ST, Kang WK, Kang JH, Park KW, Lee J, Lee SH, et al. Salvage chemotherapy with irinotecan, 5-fluorouracil and leucovorin for taxane- and cisplatin-refractory, metastatic gastric cancer. Br J Cancer. 2005;92(10):1850–4. PMCID: 2361777.
Kim SH, Lee GW, Go SI, Cho SH, Kim HJ, Kim HG, et al. A phase II study of irinotecan, continuous 5-fluorouracil, and leucovorin (FOLFIRI) combination chemotherapy for patients with recurrent or metastatic gastric cancer previously treated with a fluoropyrimidine-based regimen. Am J Clin Oncol. 2010;33(6):572–6.
Baek JH, Kim JG, Sohn SK, Kim DH, Lee KB, Song HS, et al. Biweekly irinotecan and cisplatin as second-line chemotherapy in pretreated patients with advanced gastric cancer: a multicenter phase II study. J Korean Med Sci. 2005;20(6):966–70. PMCID: 2779328.
Park SH, Choi EY, Bang SM, Cho EK, Lee JH, Shin DB, et al. Salvage chemotherapy with irinotecan and cisplatin in patients with metastatic gastric cancer failing both 5-fluorouracil and taxanes. Anticancer Drugs. 2005;16(6):621–5.
Jeong J, Jeung HC, Rha SY, Im CK, Shin SJ, Ahn JB, et al. Phase II study of combination chemotherapy of 5-fluorouracil, low-dose leucovorin, and oxaliplatin (FLOX regimen) in pretreated advanced gastric cancer. Ann Oncol. 2008;19(6):1135–40.
Kim DY, Kim JH, Lee SH, Kim TY, Heo DS, Bang YJ, et al. Phase II study of oxaliplatin, 5-fluorouracil and leucovorin in previously platinum-treated patients with advanced gastric cancer. Ann Oncol. 2003;14(3):383–7.
Shin SJ, Jeung HC, Ahn JB, Choi HJ, Cho BC, Rha SY, et al. Capecitabine and doxorubicin combination chemotherapy as salvage therapy in pretreated advanced gastric cancer. Cancer Chemother Pharmacol. 2008;61(1):157–65.
Park SH, Kim YS, Hong J, Park J, Nam E, Cho EK, et al. Mitomycin C plus S-1 as second-line therapy in patients with advanced gastric cancer: a noncomparative phase II study. Anticancer Drugs. 2008;19(3):303–7.
Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, et al. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997;15(1):261–7.
Ji SH, Lim do H, Yi SY, Kim HS, Jun HJ, Kim KH, et al. A retrospective analysis of second-line chemotherapy in patients with advanced gastric cancer. BMC Cancer. 2009;9:110. PMCID: 2671521.
Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, 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(3):215–21.
Muro K, Boku N, Shimada Y, Tsuji A, Sameshima S, Baba H, et al. Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol. 2010;11(9):853–60.
Ohtsu A. Chemotherapy for metastatic gastric cancer: past, present, and future. J Gastroenterol. 2008;43(4):256–64.
Park SH, Lee WK, Chung M, Bang SM, Cho EK, Lee JH, et al. Quality of life in patients with advanced gastric cancer treated with second-line chemotherapy. Cancer Chemother Pharmacol. 2006;57(3):289–94.
Park SH, Lim DH, Park K, Lee S, Oh SY, Kwon H, 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 2011;29:suppl; abstr 4004.
Maeda S, Sugiura T, Saikawa Y, Kubota T, Otani Y, Kumai K, et al. Docetaxel enhances the cytotoxicity of cisplatin to gastric cancer cells by modification of intracellular platinum metabolism. Cancer Sci. 2004;95(8):679–84.
Tanaka R, Ariyama H, Qin B, Shibata Y, Takii Y, Kusaba H, et al. Synergistic interaction between oxaliplatin and SN-38 in human gastric cancer cell lines in vitro. Oncol Rep. 2005;14(3):683–8.
Tanaka R, Takii Y, Shibata Y, Ariyama H, Qin B, Baba E, et al. In vitro sequence-dependent interaction between nedaplatin and paclitaxel in human cancer cell lines. Cancer Chemother Pharmacol. 2005;56(3):279–85.
Takahashi H, Sasaki Y, Saijo N, Sakurai M, Nakano H, Nakagawa K, et al. In vitro colony inhibition of carboplatin against stomach and lung cancer cell lines in comparison with cisplatin. Cancer Chemother Pharmacol. 1987;19(3):197–200.
Beer M, Cavalli F, Kaye SB, Lev LM, Clavel M, Smyth J, et al. A phase II study of carboplatin in advanced or metastatic stomach cancer. Eur J Cancer Clin Oncol. 1987;23(10):1565–7.
Preusser P, Wilke H, Achterrath W, Lenaz L, Stahl M, Casper J, et al. Phase II study of carboplatin in untreated inoperable advanced stomach cancer. Eur J Cancer. 1990;26(10):1108–9.
Raymond E, Chaney SG, Taamma A, Cvitkovic E. Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol. 1998;9(10):1053–71.
Cho BC, Kim JH, Kim CB, Sohn JH, Choi HJ, Lee YC, et al. Paclitaxel and leucovorin-modulated infusional 5-fluorouracil combination chemotherapy for metastatic gastric cancer. Oncol Rep. 2006;15(3):621–7.
Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22(9):1589–97.
Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O’Rourke M, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000;18(10):2095–103.
Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353(2):123–32.
Kodera Y, Ito S, Mochizuki Y, Fujitake S, Koshikawa K, Kanyama Y, et al. A phase II study of weekly paclitaxel as second-line chemotherapy for advanced gastric cancer (CCOG0302 study). Anticancer Res. 2007;27(4C):2667–71.
Koizumi W, Akiya T, Sato A, Yamaguchi K, Sakuyama T, Nakayama N, et al. Second-line chemotherapy with biweekly paclitaxel after failure of fluoropyrimidine-based treatment in patients with advanced or recurrent gastric cancer: a report from the Gastrointestinal Oncology Group of the Tokyo Cooperative Oncology Group, TCOG GC-0501 trial. Jpn J Clin Oncol. 2009;39(11):713–9.
Nagata N, Kimura M, Hirabayashi N, Tuburaya A, Murata T, Kondo K, et al. Phase II study of weekly paclitaxel and cisplatin combination therapy for advanced or recurrent gastric cancer. Hepatogastroenterology. 2008;55(86–87):1846–50.
Bang YJ, Kang WK, Kang YK, Kim HC, Jacques C, Zuber E, et al. Docetaxel 75 mg/m2 is active and well tolerated in patients with metastatic or recurrent gastric cancer: a phase II trial. Jpn J Clin Oncol. 2002;32(7):248–54.
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki 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. 2010;376(9742):687–97.
Bang YJ, Kang YK, Kang WK, Boku N, Chung HC, Chen JS, et al. Phase II study of sunitinib as second-line treatment for advanced gastric cancer. Invest New Drugs. 2011;29(6):1449–58
Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991;265(10):1287–9.
Kusano C, Gotoda T, Khor CJ, Katai H, Kato H, Taniguchi H, et al. Changing trends in the proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan. J Gastroenterol Hepatol. 2008;23(11):1662–5.
Acknowledgments
This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065).
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Baek, S.K., Kim, SY., Jeong, Jh. et al. Second-line chemotherapy for advanced gastric cancer in Korea. Gastric Cancer 15, 345–354 (2012). https://doi.org/10.1007/s10120-011-0114-5
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DOI: https://doi.org/10.1007/s10120-011-0114-5