• Journal of Gastric Cancer
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• v.6 no.3
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• pp.189-192
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• 2006

Acute disseminated intravascular coagulation (DIC) associated with gastric cancer is not common and has short survival of 1 to 3 weeks. Systemic chemotherapy in spite of hematologic unstability for gastric cancer may prolong survival time. A 47-year-old woman who complained of dyspnea, vaginal bleeding and easy bruisibility was diagnosed to stage IV gastric cancer with acute disseminated intravascular coagulation based on the laboratory data. She also had multiple bone metastases and bone marrow involvement. This is the first case treated with combination chemotherapy of irinotecan and cisplatin for advanced gastric cancer complicated by disseminated intravascular coagulation at the time of diagnosis, With systemic chemotherapy, some of the bleeding symptoms and the DIC process improved, even not completely recovered. However the patient died of disease progression and survival time was 12 weeks.

• BMB Reports
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• v.53 no.10
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• pp.533-538
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• 2020

Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 therapeutic antibody (anti-hDLL4) or ABL001 slightly reduced GC cell growth in monolayer culture; however, they significantly inhibited cell growth in 3D-culture, suggesting a reduction in the cancer stem cell population. Treatment with anti-hDLL4 or ABL001 also decreased GC cell migration and invasion. Moreover, the combined treatment of irinotecan with anti-hDLL4 or ABL001 showed synergistic antitumor activity. Both combination treatments further reduced cell growth in 3D-culture as well as cell invasion. Interestingly, the combination treatment of ABL001 with irinotecan synergistically reduced the GC burden in both xenograft and orthotopic mouse models. Collectively, DLL4 inhibition significantly decreased cell motility and stem-like phenotype and the combination treatment of DLL4/VEGF bispecific therapeutic antibody with irinotecan synergistically reduced the GC burden in mouse models. Our data suggest that ABL001 potentially represents a potent agent in GC therapy. Further biochemical and pre-clinical studies are needed for its application in the clinic.

• Journal of Yeungnam Medical Science
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• v.31 no.2
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• pp.82-88
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• 2014

Background: Lung cancer is the most common cause of cancer-related death worldwide and in Korea, and small cell lung cancer (SCLC) is the most deadly tumor type in the different lung cancer histology. Chemotherapy is the main strategy of the treatment for SCLC, and etoposide and platinum regimen has been the only standard chemotherapy for about 30 years. To test feasibility of weekly divided dose irinotecan and carboplatin for Korean patients is the aim of this study. Methods: Patients with histologically or cytologically confirmed extensive stage SCLC were included. Patients with limited stage (LD), who could not tolerate concurrent chemoradiotherapy were also included. All the patients received irinotecan $60mg/m^2$, carboplatin 2 area under the curve at day 1, 8, and 15 every 4 weeks. Study regimen was discontinued when the disease progressed or intolerable side effects occurred. No more than 6 cycles of chemotherapy were given. Results: Total 47 patients were enrolled, among them 9 patients were LD. Overall response rate was 74.5% (complete response, 14.9%; partial response, 59.6%). Side effects greater than grade 3 were neutropenia (25.5%), fatigue (12.8%), thrombocytopenia (8.5%), sepsis (4.3%), and pancytopenia (2.1%). There was no treatment related death. Conclusion: Weekly divided irinotecan and carboplatin regimen is effective, and safe as a first line therapy for both stage of SCLC. Large scaled, controlled study is feasible.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.11a
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• pp.87-92
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• 2006

• 한국약용작물학회:학술대회논문집
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• 2006.11a
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• pp.87-92
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• 2006

• Journal of Digestive Cancer Research
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• v.6 no.2
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• pp.64-68
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• 2018

Pancreatic ductal adenocarcinoma is a dismal prognosis and 5^th leading cause of cancer related death in Korea. A large proportion of patients are diagnosed at advanced or metastatic stage. Therefore systemic chemotherapy has become the mainstay of treatment for pancreatic cancer. For most patients advanced or metastatic pancreatic cancer that has a good Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1, we can recommend for FOLFIRINOX (leucovorin, 5-fluorouracil [5-FU], irinotecan and oxaliplatin) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel). Currently, steps towards improved therapeutic efficacy of palliative chemotherapy have been made by introducing these regimens. For patients with an ECOG PS of 2, gemcitabine monotherapy or S1 alone is recommended. The second-line therapy for patients initially treated with gemcitabine-based chemotherapy includes provide FOLFOX (leucovorin, 5-FU, and oxaliplatin), capecitabine plus oxaliplatin, and 5-FU plus liposomal irinotecan. The gemcitabine-based chemotherapy is a reasonable choice for patients treated with FOLFIRINOX. Currently, studies on selecting patients for biomarkers related to molecular biologic features of tumors are underway for the realization of precise medicine, and the development and verification of preclinical models for the development of new therapeutic agents are being carried out continuously.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3335-3341
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• 2014

Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

• 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.15 no.14
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• pp.5941-5944
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• 2014

Purpose: To highlight the potential factors that could predict the response rate of patients with metastatic colorectal cancer (mCRC) treated with pemetrexed combined chemotherapy after first- or second-line chemotherapy using the FOLFOX regimen. Materials and Methods: Between January 2007 and July 2014, 54 patients diagnosed and pathologically-confirmed with advanced colorectal cancer in Jiangsu Cancer Hospital and Research Institute, were enrolled. They received pemetrexed at a dose of $500mg/m^2$ by 10 minute infusion on day 1, repeated every 3 weeks. Doses were modified depending on nadir counts of blood cells. Combined chemotherapeutic agents included irinotecan, lobaplatin, carboplatin, oxaliplatin, gemcitabine, cis-platinum or bevacizumab. Multiple variables (age, sex, hemoglobin, platinum drugs combined, metastasis sites, LDH, ALP, CEA>40 ug/ml) reported earlier were selected. We used logistic regression analysis to evaluate relationships between these and tumor response. Results: On multivariable analysis, we found that age was significant in predicting the responsiveness to pemetrexed (p<0.05) combined with oxaliplatin. We did not find any other factors which were significantly associated with the response rate to chemotherapy with pemetrexed and irinotecan. Conclusions: By multivariate analysis, we found that age had significant impact on the responsiveness of pemetrexed when combined with oxaliplatin. Additional research based on genomic properties of host and tumors are needed to clarify markers for better selection of patients who could benefit from pemetrexed combined chemotherapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.3
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• pp.177-185
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• 2010

Introduction: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. Materials and Methods: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/ immunofluorescent analyses. Results: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. Conclusion: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.