• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2355-2359
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• 2015

Background: Combination chemotherapy of 5 fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin, mainly FOLFOX regimens, has shown considerable antitumor activity and a tolerable toxicity profile in gastric cancer. The goal of this study was to retrospectively compare the efficacy and toxicity of modified FOLFOX-6 (mFOLFOX6) regimen in advanced gastric cancer (AGC) patients with good and poor performance status (PS). Materials and Methods: AGC patients receiving the mFOLFOX6 regimen including oxaliplatin $85mg/m^2$, bolus of 5-FU $400mg/m^2$ and LV $400mg/m^2$ on the first day, followed by $2400mg/m^2$ of 5- FU as a continious infusion over 46 hour for first-line treatment were eligible for the study. Results: A total 58 patients with a median age of 59.5 (32-81) were included. The median follow up of the study was 9.2 months. Thirty patients (51.7%) with an ECOG PS 0-1 were assigned to the good PS arm, while 28 patients (48.3%) with ECOG PS 2 were in the poor PS arm. Overall response rates were 36.6 and 28.8%, respectively (p=0.91). Median PFS was 6.7 and 6.3 months in good PS and poor PS arms (p=0.50) and median OS was 9.6 and 10.4 months (p=0.55). As compared with good PS arm, poor PS arm was associated with more grade 3-4 neutropenia and anemia. Dose reduction and dose delays were also significantly higher. Conclusions: In this study, mFOLFOX6 was similarly effective in both arms. Although hematologic toxicity was significantly higher in patients with poor PS, it remained manageable. Our results suggest that this regimen may be an effective treatment option for AGC patients with poor PS.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2413-2418
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• 2015

Background: Although adjuvant chemotherapy is a standard treatment in stage III colon cancer, its benefit is not as clear for stage II patients. In this retrospective analysis, we aimed to evaluate the survival of patients with low-risk stage II colon cancer, the efficacy of adjuvant chemotherapy in high-risk stage II colon cancer patients, and prognostic factors in stage II disease. Materials and Methods: One hundred and seventeen patients who were diagnosed with stage II colon cancer between January 2006 and December 2011 were included in the study. Patients were stratified into two groups as being low-risk and high-risk according to risk factors for stage II disease. Adjuvant 5-fluorouracil-based chemotherapy were administered to the patients with risk factors. Results: Ninety-four patients were treated with adjuvant chemotherapy due to high risk factors and 23 were monitored without treatment. Median follow-up time was 43 months. In terms of disease free survival and overall survival, adjuvant chemotherapy did not provide a statistically significant difference. Univariate analysis demonstrated that bowel obstruction was the major risk factor for shortened disease-free survival, while bowel perforation and perineural invasion were both negative prognostic factors for overall survival. Conclusions: The recommendation of adjuvant chemotherapy for stage II colon cancer is not clear. In our study, it was found that adjuvant chemotherapy did not contribute to survival in high-risk stage II patients. Due to the fact that prognosis of stage II patients is good, many more patients will be needed for statistically significant differences in survival. Adjuvant chemotherapy containing 5 fluorouracil is being used to high-risk stage II patients although it is not a standard treatment approach.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6585-6590
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• 2013

Background: Although FOLFOX (infusional fluorouracil/leucovorin plus oxaliplatin) is established as a standard chemotherapeutic regimen, the long term efficacy of adjuvant XELOX (oral capecitabine plus intravenous oxaliplatin) in Asian colorectal cancer (CRC) patients remains anecdotal. Moreover, uncertainties persist as to whether pharmacogenetic differences in Asian populations preclude equally tolerable and effective administration of these drugs. Method: One hundred consecutive patients with resected colorectal cancer received adjuvant XELOX (oxaliplatin 130 $mg/m^2$ on day 1 plus capecitabine 900 $mg/m^2$ twice daily on day 1 to 14 every 3 weeks for 8 cycles) at Queen Mary Hospital, Hong Kong. Endpoints monitored during follow-up were disease-free survival (DFS) and disease recurrence, overall survival (OS) and adverse events (AEs). Results: The median patient age was 56 years, 56% were diagnosed with rectal cancer and 44% with colonic cancer. After a median follow-up of 4.3 years (95% confidence interval, 3.2-4.7), 24 recurrences were confirmed including 13 patients who died due to progressive disease. Four-year DFS was 81% in colon cancer patients and 67% in rectal cancer patients (p=0.06 by log-rank test). For the cohort as a whole, OS was 90% at 3 years and 84% at 5 years. Treatment-related AEs led to early withdrawal in four patients. The commonest non-hematological AEs were neuropathy (91%), hand-foot syndrome (49%) and diarrhea (46%), while the commonest grade 3/4 AEs were neutropenia (11%) and diarrhea (10%). Conclusion: These results confirm the favourable long term survival benefit with good tolerability in using adjuvant XELOX in treating East Asian colorectal cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5681-5686
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• 2015

Background: Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still firstline chemotherapy. Howeve,r gemcitabine+fluorouracil regimens are also licensed and widely used worldwide. Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone. Materials and Methods: A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials. Results: A total of 12 studies were included in the present analysis, with a total of 3,038 patients recruited. The studies were divided into three subgroups including 5-FU / CAP / S-1 combined with gemcitabine. For the primary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantly better outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression free survival (PFS) also provided a significant result for the combined therapy in a total of 8 trials (2,130 patients) (HR, 0.74; 95% CI, 0.63-0.86). With subgroup analysis according to the method of dosing delivery, we found that in the injection group with 3 trials (889 patients), a negative result was found (HR, 0.93; 95% CI, 0.77-1.12); while a positive result was observed in the oral group with 9 trials (2,149 patients) (HR, 0.87; 95% CI, 0.80-0.95). Conclusions: Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy.

• Polymer(Korea)
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• v.31 no.5
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• pp.447-453
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• 2007

In this study, we fabricated recrystallized PLGA (rPLGA) particles using the vacuum drying method. In order to investigate an applicability of the rPLGA particles for controlled release system of 5-fluorouracil (5-FU) loaded PLGA wafer, we prepared three different wafers using; 1) untreated PLGA (uPLGA), 2) rPLGA, and 3) uPLGA and rPLGA (4 : 1, 1 : 1 or 1 : 4). The rPLGA particles were characterized using NMR, IR and GPC to compare with uPLGA particles. The surface and cross section morphology of the prepared wafers were observed by the scanning electron microscope. The release profile of the 5-FU loaded wafer was measured by HPLC. The 5-FU/rPLGA wafer released the incorporated 5-FU in a sustained manner with low initial burst compared to 5-FU/uPLGA. These results showed that the ratio of pure PLGA/recrystallized PLGA can affect the release behaviors.

• Journal of Haehwa Medicine
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• v.4 no.1
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• pp.211-223
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• 1995

The antitumor effect of 柴胡(Bupleuri Radix : BP), 茵陳(Artemisiae capillaris Herba; ACH) 및 蒲公英(Taraxaci Herba; TH) and 蒲公英 EE層(Ethyl ether layer of TH; EETH) on human hepatocytes such as Hep G2, PLC and Hep 3B, and synergistic action with the anticancer drugs, that is, mitomycin(MMC), cisplatin(CPT) and 5-fluorouracil(5-FU) were studied by the method of MTT. The results were obtained as follows: 1. $IC_{50}$ against Hep G2, PLC and Hep 3B was $15.5{\mu}g/ml$, $25.4{\mu}g/ml$ and 31.25 in MMC, $92.5{\mu}g/ml$, $50.2{\mu}g/ml$ and $62.5{\mu}g/ml$ in CPT and $125{\mu}g/ml$ in 5-FU respectively. 2. Cytotoxic effect on Hep G2 was obvious in BP-treated group, synergistic action was most effective in TH-treated group or with MMC. 3. Cytotoxic effect on Hep 3B was obvious in ACH-treated group, synergistic action was most effective in ACH-treated group or with MMC. 4. Cytotoxic effect on PLC was obvious in ACH-treated group, synergistic action was most effective in TH-treated group or with MMC. From above results it was concluded that ACH showed the best antitumor effect against PLC and Hep 3B, BP aganst Hep G2 and also synergistic effect was most effective with MMC, which indicates that it is necessary to seperate the antitumor substances in ACH.

• Journal of Digestive Cancer Research
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• v.5 no.2
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• pp.125-129
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• 2017

A 38-year-old man presented with abdominal discomfort and was diagnosed as type 3 advanced gastric cancer with multiple liver and lung metastases (Stage IV). Endoscopic forcep biopsy revealed moderately differentiated adenocarcinoma, which stained positive HER2 (Human epidermal growth factor receptor) on immunohistochemistry. We started chemotherapy with FP (5-Fluorouracil plus Cisplatin) plus trastuzumab. After 6 cycles of FP plus trastuzumab chemotherapy, there were partial response in the liver, lung and lymph nodes metastasis. Especially, metastatic lung lesions showed remarkable improvement. Chemotherapy with FP plus trastuzamab was effective for HER2 positive advanced cancer with multiple liver and lung metastases. Through active research on target therapy about advanced gastric cancer, we expect to improve the survival rate and quality of life of patients with advanced gastric cancer who can not undergo curative resection.

• Journal of Digestive Cancer Research
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• v.5 no.2
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• pp.113-119
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• 2017

Background: Second line chemotherapy is often considered in advanced gastric cancers. We assessed irinotecan in combination with fluorouracil in patients experienced diseases progression after first line chemotherapy. Methods: Prospective trial was done at 7 centers in republic of Korea. Patients aged 18 years or older with advanced gastric adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy were assigned to receive irinotecan 180 mg/m² and 5-fluorouraicl 400 mg/m² intravenously bolus injection on days 1 and leucovorin 200 mg/m² for 2 hours and 5-fluorouracil 600 mg/m² for 22 hours intravenously infusion on day 2 of a 14-day cycle (FOLFIRI group). The primary endpoint was objective tumor response (OR). Efficacy analysis was by per-protocol, and safety analysis included all patients who received at least one treatment with study drug. Results: Between January 1, 2014 and December 31, 2016, 28 patients were assigned to FOLFIRI treatment. Of those 20 patients were completed the study protocol. Per-protocol analysis, two patients among 20 subjects (10.0%) showed partial response. Overall survivals of FOLFIRI group; median 10.1 months [95% CI 4.9-15.3] Grade 3 and higher adverse event that occurred about 5%, but grade 3 or higher febrile neutropenia or life threatening complication was not reported. Conclusion: Combination chemotherapy with irinotecan, 5-FU, and LV is feasible in gastric cancer patients previously treated with platinum-based chemotherapy

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4719-4722
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• 2016

Background: Glutathione S-transferase M1 (GSTM1) is involved in the detoxification of carcinogenic agents. DNA copy number variants of GSTM1 may be associated with cancer progression and may result in reduced survival time of various cancers. Determination of DNA copy number variants was here used to assess the association between GSTM1 copy number variant and pathological status and survival time of colorectal-cancer patients treated with 5-fluorouracil-based chemotherapy. Methods: One hundred thirteen Thai colorectal-cancer patients were investigated for GSTM1 copy number variant by real-time PCR. Relationships between gene copy number variants and clinico-pathological parameters were determined. Result: Associations were evident between GSTM1 copy number and stage of tumor (P = 0.026) and metastasis at diagnosis (P = 0.049), with odds ratio values of 0.2 and 0.3 respectively. Conclusions: GSTM1 copy number variant was here not related with reduced overall survival for the colorectal-cancer patients receiving 5-FU-based chemotherapy.