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Japanese Journal of Clinical Oncology Advance Access originally published online on October 8, 2007
Japanese Journal of Clinical Oncology 2007 37(10):744-749; doi:10.1093/jjco/hym103
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© 2007 Foundation for Promotion of Cancer Research

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

Seong-Geun Kim, Sung Yong Oh, Hyuk-Chan Kwon, Suee Lee, Jung Hwan Kim, Sung-Hyun Kim and Hyo-Jin Kim

Departments of Internal Medicine, Dong-A University College of Medicine, Busan, Korea

For reprints and all correspondence: Hyo-Jin Kim, Department of Internal Medicine, Dong-A University College of Medicine, 3-1 Dongdaeshin-dong, Seo-gu, Busan, 602-715, Korea. E-mail: kimhj{at}dau.ac.kr

Received April 22, 2007; accepted June 22, 2007


   Abstract
TOP
 Abstract
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Objective: This phase II study was designed to assess the safety and efficacy of a modified FOLFIRI regimen (irinotecan with bi-weekly, low dose leucovorin (ldLV) and bolus and continuous infusion with 5-fluorouracil (5-FU)) as a salvage therapy for patients with advanced or metastatic gastric cancer.

Methods: Patients were treated with irinotecan 150 mg/m2 on day 1 and received ldLV 20 mg/m2 followed by 5-FU 400 mg/m2 (bolus) and 5-FU 600 mg/m2 (22 h continuous infusion) on days 1 and 2 every 14 days.

Results: A total of 36 patients were assigned to treatment. The median patient age was 55 years (range 31–70), and 55.6% (20/36) of the patients had performance status (ECOG) of 0 or 1.The median follow-up duration was 15.5 (range 2.6–36.4) months. Of the 30 patients evaluated for their tumor response, three achieved a partial response, with an overall response rate of 10.0% (95% CI 0.0–21.0%). Eleven patients (36.7%) showed stable disease. The median time to progression was 3.3 (95% CI 2.0–4.6) months, and the median overall survival time was 10.9 (95% CI 6.1–15.7) months. The median number of cycles of modified FOLFIRI treatment was 3 (range 1–9 cycles). Grade III or IV neutropenia was observed in 23 cycles (17.6%), and febrile neutropenia occurred in three cycles (2.3%). Grade III nausea/vomiting was found in one patient (2.8%). There was one episode of UGI bleeding, but there were no treatment-related deaths.

Conclusion: The modified FOLFIRI regimen described here appears a safe and feasible salvage therapy in advanced gastric cancer patients.

Key Words: irinotecan • low-dose leucovorin • 5-fluorouracil • advanced gastric cancer


   INTRODUCTION
TOP
 Abstract
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Gastric cancer is the most common malignancy in Korea (1), and it remains the second leading cause of cancer-related deaths worldwide (2). Although the incidence of gastric cancer has been declining over the past three decades, it is often diagnosed in locally advanced or metastatic diseases. Therefore, less than 30% of patients will undergo a curative resection, and about 35% of the patients who do undergo surgery will remain alive for 5 years (3). Only 10% of patients with advanced gastric cancer who undergo chemotherapy survive for 2 years (4). As a consequence, the overall 5-year survival rate for patients with advanced gastric cancer is between 5 and 10% (5).

Four prospective randomized trials have demonstrated an increase in survival, from 3 months to about 10 months, with chemotherapy over best supportive care alone (6). Two studies have shown the benefit of using combination regimens, such as 5-Fluorouracil (5-FU), doxorubicin and methotrexate (FAMTX) or etoposide, leucovorin (LV) and 5-FU (ELF), for the treatment of advanced gastric cancer (7,8). In 1999, Waters and his colleagues (9) showed that the combination of epirubicin, ciplatinum and infusional 5-FU (ECF) was highly effective in the first-line treatment of advanced gastric cancer. However, most cases of locally advanced or metastatic gastric carcinoma ultimately progress and eventually result in patient death, regardless of the patient's initial response to chemotherapy. For these patients, there is still no standard palliative chemotherapy regimen or other treatment option currently available. Therefore, we are pressingly in need of highly active new agents and novel combinations of these drugs.

Irinotecan is a derivative of camptothecin. Camptothecins specifically interact with the enzyme topoisomerase I, which relieves the torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent these single-strand breaks from resealing. Current research suggests that the cytotoxicity of irinotecan is due to the double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38 (10,11). Single-agent irinotecan has shown response rates of 13% in advanced gastric cancer (12). With respect to combination therapy, Boku et al. (13) reported a response rate of 27% and SD in 20% of patients treated with 70 mg/m2 of irinotecan on days 1 and 15, and 80 mg/m2 of cisplatin on day 1. These cycles were repeated every 4 weeks in 15 pre-treated good-performance-status patients. However, this regimen produced significant toxicity, with 57% of the patients having grade 4 neutropenia and 20% of the patients having grade 4 diarrhea. The second course was delayed in 56% of the cases, and the treatment was not administered at all in 23% of cases due to the toxicity of the treatment.

More recently, phase II studies with irinotecan plus 5-FU and leucovorin (FOLFIRI) as a first-line regimen showed an response rate (RR) of 40% with a median survival time between 10.7 and 12.6 months (14). Another multicenter randomized phase II study was conducted in an effort to compare the effects of LV5FU2 administered alone or in combination with cisplatin or irinotecan in patients with previously untreated metastatic gastric or cardial adenocarcinoma. The overall response rates were 13, 27 and 40%, respectively. The median progression-free survival and overall survival times were 3.2 and 6.8 months with LV5FU2, respectively; 4.9 and 9.5 months with LV5FU2-cisplatin, respectively; and 6.9 and 11.3 months with LV5FU2-irinotecan, respectively (15).

This phase II study was designed to assess the safety and efficacy of a modified FOLFIRI regimen (irinotecan with bi-weekly, low dose leucovorin (ldLV) and bolus and continuous infusion with 5-fluorouracil) as a salvage therapy for patients with advanced or metastatic gastric cancer.


   PATIENTS AND METHODS
TOP
 Abstract
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 References
 
Eligibility
The patients had to have a histologically confirmed diagnosis of adenocarcinoma of the stomach and at least one measurable lesion. This study included patients who had received at least one previous palliative chemotherapy regimen or radiotherapy and who showed progression after adjuvant chemotherapy given more than 4 weeks prior to registration in this study. Eastern Cooperative Oncology Group (ECOG) performance status was 0–2 in all of the patients. Patients were required to have no central nervous system metastases, no active infections, no serious or uncontrolled concurrent medical illness, and no previous history of other malignancies. Adequate hepatic, renal and bone marrow function was essential. The study was approved by the local ethics committee and informed consent was obtained from all patients before study entry.

Treatment Protocol
Chemotherapy was administered through a chemoport placed in the right subclavian vein or directly into a peripheral vein. Irinotecan was administered at 150 mg/m2 (2 h infusion) on day 1, and the patients received 20 mg/m2 of LV (over 10 min), followed by 400 mg/m2 of 5-FU (bolus) and 600 mg/m2 of 5-FU (22 h continuous infusion) on days 1 and 2, every 14 days. We do not routinely use atropine subcutaneously to prevent cholinergic syndrome associated with irinotecan. Dexamethasone, ondansetron and metoclopramide were given as antiemetic prophylaxis before starting chemotherapy. Loperamide was prescribed for patients who developed diarrhea (initially 4 mg after the first diarrhea, followed by 2 mg every 4 h for at least the first 12 h), and adequate fluid therapy was added. Treatment was terminated if there were signs of disease progression, unacceptable toxic effects or if the patient refused to undergo further treatment.

Dose Modification for Toxicity
We evaluated and graded all adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0). Treatment was delayed by one week in cases of neutropenia (absolute neutrophil count <1.0 x 109/l), diarrhea grade >1 or stomatitis grade >1. The dose of 5-FU was reduced by 20% in the subsequent courses for patients who experienced diarrhea or mucositis of CTCAE grade 3 or higher. For hematological toxicities of grade 3 or higher, the dose of irinotecan was reduced by 20%.

Assessment of Response
Physical examination, complete blood counts, chemistry and chest X-rays were performed after each cycle. Response was assessed using WHO criteria (16). Computed tomography (CT) scans were repeated every three cycles, or earlier in cases of clinical deterioration. Only patients with bidimensionally measurable lesions (largest diameter 2 cm or greater) on the CT scan were evaluated for tumor response. Complete response (CR) was defined as the complete disappearance of all assessable disease for at least 4 weeks. A partial response (PR) indicated a decrease of at least 50% in the sum of the products of the diameters of the measurable lesions for at least 4 weeks. Stable disease (SD) was defined as a decrease of less than 50% or an increase of less than 25% in the size of the tumor, and progressive disease (PD) was defined as an increase of at least 25% in the size of the tumor or the appearance of new neoplastic lesions.

Statistical Methods
This trial was designed to detect a response rate of 30% as compared with a minimal, clinically meaningful response rate of 10%. A two-stage optimal design as proposed by Simon was adopted, with a statistical power of 80% to accept the hypothesis and 5% significance to reject the hypothesis. Allowing for a follow-up loss rate of up to 10%, the total sample size required was 35 patients with measurable disease. The response duration was defined as the period of time from the initial date of response to treatment to the time of disease progression or recurrence. The time to progression and overall survival were calculated from the initiation of treatment to the first observation of disease progression or death, respectively. All data were analyzed using SPSS software (version 12.0, Chicago, IL, USA).


   RESULTS
TOP
 Abstract
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 References
 
Patients Characteristics
Between September 2004 and June 2006, a total of 36 patients were assigned to treatment at the Department of Internal Medicine at Dong-A University Medical Center, Busan, South Korea. Thirty patients were evaluated for response to treatment and toxicity. The male to female ratio was 23:13. The median patient age was 55 years (range 31–70), and 55.6% (20/36) of the patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eighteen patients had previously undergone chemotherapy on more than two occasions, and 12 patients had at least two organs involved. The basal characteristics of the patients are listed in Table 1.


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  		Table 1. Patient characteristics

 
Prior Treatments
Regardless of the first- or second-line chemotherapy, the FOLFOX regimen was used to treat all 30 patients. The capecitabine/cisplatin regimen and oral 5-FU were respectively given to eight patients before the modified FOLFIRI regimen was administered. 5-FU/cisplatin, paclitaxel/cisplatin and dorcetaxel/cisplatin were used in six patients, four patients and one patient, respectively. Table 2 shows the regimens used prior to modified FOLFIRI salvage chemotherapy.


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  		Table 2. Previous chemotherapy

 
Response
The median follow-up duration was 15.5 months (range 2.6–36.4 months). Of the 30 patients evaluated for their tumor response, three achieved a partial response, with an overall response rate of 10.0% (95% confidence interval (CI) 0.0–21.0%). Eleven patients (36.7%) showed stable disease and 16 patients (53.3%) progressed during the course of treatment. The median time to progression was 3.3 months (95% CI 2.0–4.6 months) (Fig. 1), and the median overall survival time was 10.9 months (95% CI 6.1–15.7 months) (Fig. 2). All three of the patients who responded to treatment were male, and they had all been treated with the FOLFOX regimen prior to the modified FOLFIRI salvage chemotherapy. These patients also had just one metastatic organ site. One patient had metastasis to the colon and the others had hepatic involvement.


Figure 1
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  		Figure 1. Time to progression curve.

 

Figure 2
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  		Figure 2. Overall survival curve.

 
Toxicity
Thirty-six patients received a total of 131 treatment cycles. The median number of cycles of modified FOLFIRI treatment was three (range 1–9 cycles). The toxicities observed during the treatment are listed in Table 3. Grade I or II anemia and grade I or II thrombocytopenia were observed in 47 cycles (35.8%) and eight cycles (6.1%), respectively. Grade III or IV neutropenia was observed in 23 cycles (17.6%), and febrile neutropenia occurred in three cycles (2.3%). Grade I or II nausea/vomiting was observed in five patients (13.9%) and grade III nausea/vomiting was found in one patient (2.8%). Surprisingly, only one patient (2.8%) with grade II diarrhea was reported. Two patients (5.6%) experienced grade II or III stomatitis. Moreover, there was one episode of UGI bleeding in our study, but there were no treatment-related deaths.


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  		Table 3. Toxicity

 

   DISCUSSION
TOP
 Abstract
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
References
 
In 1996, Saltz et al. (17) reported that the combination of irinotecan 125 mg/m2, 5-FU 500 mg/m2 and leucovorin (LV) 20 mg/m2 was feasible and tolerable in patients with advanced solid tumors. The maximum tolerated dose of irinotecan, when given every 2 weeks in combination with the LV5FU2 fixed regimen to patients with colorectal cancer refractory to 5-FU, was 180 mg/m2; however, antitumor efficacy was observed at lower dose levels (18). Therefore, we used 150 mg/m2 rather than 180 mg/m2 of irinotecan.

To determine the most effective dose of leucovorin (LV) within a weekly bolus fluorouracil (FU) schedule, Jager et al. (19) conducted a randomized multicenter trial to compare the therapeutic effects and toxicity of high-dose LV vs low-dose LV combined with FU at equal doses in advanced colorectal cancer. High-dose LV/5FU is not superior to low-dose LV/5FU within a weekly treatment schedule, and the response rates and survival rates were comparable in both treatment groups. Treatment-related toxicity was higher in the high-dose LV group. High-dose LV plus bolus and continuous-infusion 5-FU twice monthly (LV5FU2) improved the response rate and progression-free survival (PFS), and this regimen generated less toxicity than the 5-day Mayo Clinic regimen (20). In addition, Ducreaux revealed that ldLV5FU2 was an active, easier-to-use and less expensive schedule of infusional 5-FU than classical LV5FU2 or weekly HD-5FU (21). Based on these findings, we used low-dose LV in our study. Oxaliplatin including modified FOLFOX regimen has also been observed to have the same efficacy and to be more tolerable in first-line treatment in advanced gastric cancer at our hospital (22).

Compared with the 5-FU, etoposide, in the cisplatin (FEP) salvage chemotherapy trial that was conducted in our institution, a relatively lower RR was obtained using the modified FOLFIRI salvage regimen. The overall survival (OS), however, was nearly twice as long in the modified FOLFIRI salvage regimen than in FEP. Similarly, when it comes to salvage chemotherapy with irinotecan, 5-FU and leucovorin for taxane- and cisplatin-refractory metastatic gastric cancer, our study showed superior OS and comparable RR (Table 4). As a result of the modified treatment schedule used in this study, the toxicity profile was not severe, with grade 1 and 2 anemia representing the leading toxicity observed in 47% of the patients. The occurrence of grade 3 or 4 neutropenia is probably related to bone marrow suppression by the cumulative dose of prior chemotherapy or radiotherapy and the bolus 5-FU administration in the modified FOLFIRI regimen. The most common non-hematological toxicity observed in our study was nausea/vomiting (13.9%), followed by diarrhea (2.8%). In contrast to our results, Bouche et al. (15) reported that high rates of irinotecan-related diarrhea occurred in patients with advanced and metastatic gastric cancer treated with the FOLFIRI regimen. The decreased rates of diarrhea observed in our study may be due to both the use of a lower dose of irinotecan and LV and racial differences between Asian and European populations.


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  		Table 4. Comparison of efficacy in AGC salvage regimens

 
Although the RR (10%) in our study was relatively low, the median time to progression (TTP) of the 30 patients was 3.3 months, and the median OS was 10.9 months. These results are comparable to those reported from other combination regimens such as irinotecan/cisplatin, FOLFIRI and FOLFOX (23,24).

We analyzed univariables such as age, gender, ECOG performance, number of metastatic organs and the number of previous chemotherapy treatments in order to evaluate the prognostic factors for TTP and OS. ECOG performance (ECOG 0–1) showed a statistical benefit in TTP (P = 0.0470), and fewer than two previous chemotherapy treatments was associated with more prolonged OS (P = 0.0391). However, this statistical benefit in OS should be interpreted with caution because it might be in danger of falling into lead-time bias.


   Acknowledgments
 
This work was supported by the Dong-A University Research Fund in 2006.

Conflict of interest statement

None declared.


   References
TOP
 Abstract
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 References
 
1 Bae JM, Park JG. Annual report of the Korea Central Cancer Registry Program 2000: based on registered data from 131 hospitals. Cancer Res Treat (2002) 34:77–83.

2 Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics 2002. CA cancer J Clin (2005) 55:74–108.[Abstract/Free Full Text]

3 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. Br J Cancer (1999) 79:1522–30.[CrossRef][Web of Science][Medline]

4 Schipper DL, Wagener DJ. Chemotherapy of gastric cancer. Anticancer drugs (1996) 7:137–49.[CrossRef][Medline]

5 Karpeh MS, Kelsen DP, Tepper JE. Cancer of the stomach, in DeVita VT, Hellman S, Rosenberg SA. Cancer; Principles and Practice on Oncology. (2001) (6th edn). Philadelphia, PA: Lippincott, Williams & Wilkins. 1092–126.

6 Wilson D, Hillery L, Geh JI, Wilson D, Hiller L, Geh JI. Review of second-line chemotherapy for advanced gastric adenocarcinoma. Clin Oncol (2005) 17:81–90.[CrossRef][Web of Science]

7 Wils JA, Klein HO, Wagener DJ, Bleiberg H, Reis H, Korsten F, et al. Sequential high-dose methotrexate and fluorouracil combined with doxorubicin: A step ahead in the treatment of advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group. J Clin Oncol (1991) 9:827–31.[Abstract]

8 Vanhoefer U, Rougier P, Wilke H, Vanhoefer U, Rougier P, Wilke H, et al. Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol (2000) 18:2648–57.[Abstract/Free Full Text]

9 Waters JS, Norman A, Cunningham D, Scarffe JH, Webb A, Harper P, et al. Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer (1999) 80:269–72.[CrossRef][Web of Science][Medline]

10 Hsiang YH, Lihou MG, Liu LF. Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin. Cancer Res (1989) 49:5077–82.[Abstract/Free Full Text]

11 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) 86:836–42.[Abstract/Free Full Text]

12 Futatsuki K, Wakui A, Nakao I, Sakata Y, Kambe M, Shimada Y, Yoshino M, Taguchi T, Ogawa N. Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer: CPT-11 Gastrointestinal Cancer Study Group. Gan To Kagaku Ryoho (1994) 21:1033–8.[Medline]

13 Boku N, Ohtsu A, Shimada Y, Shirao K, Seki S, Saito H, et al. Phase II study of a combination of irinotecan and cisplatin against metastatic gastric cancer. J Clin Oncol (1999) 17:319–23.[Abstract/Free Full Text]

14 Pozzo C, Barone C, Szanto J, Padi E, Peschel C, Bukki J, et al. combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophagealgastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol (2004) 15:1773–81.[Abstract/Free Full Text]

15 Bouche O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, et al. Randomized multicenter phase II trial of a bi-weekly 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 (2004) 22:4319–28.[Abstract/Free Full Text]

16 Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981. 47:207–14.

17 Saltz LB, Kanowitz J, Kemeny NE, Schaaf L, Spriggs D, Staton BA, et al. Phase I clinical and pharmacokinetic study of irinotecan, fluorouracil, and leucovorin in patients with advanced solid tumors. J Clin Oncol (1996) 14:2959–67.[Abstract]

18 Ducreux M, Ychou M, Seitz JF, Bonnay M, Bexon A, Armand JP, et al. Irinotecan combined with bolus fluorouracil, continuous infusion fluorouracil, and high-dose leucovorin every two weeks (LV5FU2 regimen): A clinical dose-finding and pharmacokinetic study in patients with pretreated metastatic colorectal cancer. J Clin Oncol (1999) 17:2901–08.[Abstract/Free Full Text]

19 Jager E, Heike M, Bernhard H, Klein O, Bernhard G, Lautz D, et al. weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: Results of a randomized multicenter trial. Study group for palliative treatment of metastatic colorectal cancer study protocol 1. J Clin Oncol (1996) 14:2274–9.[Abstract]

20 de Gramont A, Bosset JF, Milan C, Rougier P, Bouche O, Etienne PL, et al. Randomized trial comparing monthly low dose leucovorin and fluorouracil bolus with bimonthlyhigh dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer. A French intergroup study. J Clin Oncol (1997) 15:808–15.[Abstract/Free Full Text]

21 Ducreaux M, Bouche O, Pignon JP, Mousseau M, Raoul JL, Cassan P, et al. Randomized trial comparing three different schedules of infusional 5FU and raltitrexed alone in first line metastatic colorectal cancer. Final results of the Federation Francophone de Cancerologie Digestive 9601 trial. Ann Oncol (2002) 13((Suppl 5)):71.[Free Full Text]

22 Oh SY, Kwon HC, Seo BG, Kim SH, Kim JS, Kim HJ. A Phase II study of oxaliplatin with low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced gastric cancer. Acta Oncol (2007) 46:336–41.[CrossRef][Web of Science][Medline]

23 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) 20:966–70.[Web of Science][Medline]

24 Assersohn L, Brown G, Cunningham D, Ward C, Oates J, Waters JS, et al. Phase II study of irinotecan and 5-fluorouracil/leucovorin in patients with primary refractory or relapsed advanced oesophageal and gastric carcinoma. Ann Oncol (2004) 15:64–9.[Abstract/Free Full Text]

25 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) 92:1850–4.[CrossRef][Web of Science][Medline]

26 Chung JH, Bae YZ, Kim SH, Moon CH, Chung JY, Kwon HC, et al. Salvage treatment of advanced gastric cancer using FEP (5-FU, etoposide, cisplatin) combination chemotherapy. Cancer Res Treat (2002) 34:382–7.


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M.-D. Seo, K.-W. Lee, J. H. Lim, H. G. Yi, D.-Y. Kim, D.-Y. Oh, J. H. Kim, S.-A. Im, T.-Y. Kim, J. S. Lee, et al.
Irinotecan Combined with 5-Fluorouracil and Leucovorin as Second-line Chemotherapy for Metastatic or Relapsed Gastric Cancer
Jpn. J. Clin. Oncol., September 1, 2008; 38(9): 589 - 595.
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