• Title, Summary, Keyword: irinotecan

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A network meta-analysis of the short-term efficacy of five chemotherapy regimens based on cisplatin and fluorouracil for esophagogastric junctional adenocarcinoma

  • Wang, Cong;Song, Dong-Jian;Xu, Zhi-Li;Xie, Shu-Ping;Hu, Jun-Hong
    • Experimental and Molecular Medicine
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    • v.49 no.9
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    • pp.5.1-5.10
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    • 2017
  • The primary purpose of this study was to explore the short-term efficacy of different cisplatin and fluorouracil-based chemotherapy regimens in the treatment of patients with esophagogastric junctional adenocarcinoma (EGJA) using a network meta-analysis (NMA). Randomized controlled trials (RCTs) related to chemotherapy regimens based on cisplatin and fluorouracil for EGJA were included from the PubMed, EMBASE and Cochrane Library electronic databases (from inception to June 2016). Direct and indirect evidence were combined to calculate the pooled odds ratio (OR) and its 95% confidence interval (95% CI) as well as to draw the surface under the cumulative ranking (SUCRA) curves. This NMA finally enrolled ten eligible RCTs with the following five regimens: cisplatin plus fluorouracil (cisplatin+fluorouracil), cisplatin+fluorouracil-based chemotherapy (cisplatin+fluorouracil+docetaxel/epirubicin/irinotecan), fluorouracil-based chemotherapy (fluorouracil+docetaxel/doxorubicin/ methotrexate/irinotecan), cisplatin-based chemotherapy (cisplatin+docetaxel/epirubicin/irinotecan/capecitabine/s-1) and other drug-based chemotherapy (docetaxel/irinotecan/capecitabine). These results revealed that compared with a cisplatin+fluorouracil-based chemotherapy regimen, the fluorouracil-based chemotherapy regimen had a lower overall response rate (ORR) and partial response (PR) for EGJA patients (ORR: OR = 0.43, 95% CI = 0.22-0.86; PR: OR = 0.46, 95% CI = 0.23-0.91). Cluster analyses suggested that the cisplatin+fluorouracil-based chemotherapy regimen had the best short-term efficacy for EGJA in terms of the complete response (CR), PR, ORR, stable disease (SD) and progression disease (PD). Our results indicated that cisplatin+fluorouracil-based chemotherapy regimens may have the best short-term efficacy in the treatment of EGJA.

Weekly irinotecan and carboplatin for patients with small cell lung cancer (소세포 폐암 환자에서 이리노테칸, 카보플라틴 주별 분할 항암요법의 효과)

  • Lee, Hye-Won;Jeong, Eu Gene;Kim, Dong Hyun;Lee, Hyuk;Kang, Bo Hyoung;Um, Soo-Jung;Roh, Meesook;Son, Choonhee
    • Yeungnam University Journal of Medicine
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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.

Phase II Study of Irinotecan and Cisplatin Combination Chemotherapy in Metastatic, Unresectable Esophageal Cancer

  • Kim, Miso;Keam, Bhumsuk;Kim, Tae-Min;Kim, Hoon-Gu;Kim, Jin-Soo;Lee, Sung Sook;Shin, Seong Hoon;Kim, Min Kyoung;Park, Keon Uk;Kim, Dong-Wan;Yun, Hwan Jung;Lee, Jong Seok;Heo, Dae Seog
    • Cancer Research and Treatment
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    • v.49 no.2
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    • pp.416-422
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    • 2017
  • Purpose The objective of this multicenter phase II study was to evaluate the efficacy and safety of irinotecan and cisplatin combination chemotherapy in metastatic, unresectable esophageal cancer. Materials and Methods Patients were treated with irinotecan $65mg/m^2$ and cisplatin $30mg/m^2$ on days 1 and 8 of each 21-day treatment cycle. The primary endpoint was response rate, and secondary endpoints were survival, duration of response, initial metabolic response rate, and toxicity. Results A total of 27 patients with squamous cell histology were enrolled in the study. The median age of the patients was 61 years. The objective response rate of the 20 patients in the per-protocol group was 30.0% (90% confidence interval [CI], 13.2 to 46.9). The median follow-up duration was 10.0 months, and the median progression-free survival and overall survival were 4.5 months (95% CI, 1.6 to 6.2) and 8.8 months (95% CI, 4.7 to 10.5), respectively. Four of 13 patients (30.8%) evaluated showed initial metabolic response. The median duration of response for partial responders was 5.0 months (range, 3.4 to 8.0 months). The following grade 3/4 treatment-related hematologic toxicities were reported: neutropenia (40.7%), anaemia (22.2%), and thrombocytopenia (7.4%). Two patients experienced febrile neutropenia. The most common grade 3/4 non-hematologic toxicities were asthenia (14.8%) and diarrhoea (11.1%). Conclusion Irinotecan and cisplatin combination chemotherapy showed modest anti-tumour activity and manageable toxicity for patients with metastatic, unresectable esophageal cancer.

Synergistic antitumor activity of a DLL4/VEGF bispecific therapeutic antibody in combination with irinotecan in gastric cancer

  • Kim, Da-Hyun;Lee, Seul;Kang, Hyeok Gu;Park, Hyun-Woo;Lee, Han-Woong;Kim, Dongin;Yoem, Dong-Hoon;Ahn, Jin-Hyung;Ha, Eunsin;You, Weon-Kyoo;Lee, Sang Hoon;Kim, Seok-Jun;Chun, Kyung-Hee
    • 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.

A Case of Gastric Cancer Presenting Acute Disseminated Intravascular Coagulation Palliated with Combination Chemotherapy of Irinotecan and Cisplatin (위암과 동반된 급성 파종성 혈관 내 응고증에 대하여 Irinotecan, Cisplatin 복합화학요법으로 완화요법을 시행한 1예)

  • Lee, Sang-Hoon;Woo, In-Sook;Kim, Seon-Young;Song, Myung-Jun;Rho, Sang-Young;Koh, Su-Jin;Lee, Myung-Ah;Kang, Jin-Hyoung;Hong, Young-Seon;Choi, Myung-Gyu;Lee, Kyng-Shik
    • 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.

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Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-Line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer

  • Yoo, Changhoon;Han, Boram;Kim, Hyeong Su;Kim, Kyu-pyo;Kim, Deokhoon;Jeong, Jae Ho;Lee, Jae-Lyun;Kim, Tae Won;Kim, Jung Han;Choi, Dae Ro;Ha, Hong Il;Seo, Jinwon;Chang, Heung-Moon;Ryoo, Baek-Yeol;Zang, Dae Young
    • Cancer Research and Treatment
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    • v.50 no.4
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    • pp.1324-1330
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    • 2018
  • Purpose Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC. Materials and Methods Chemotherapy-naive patients with histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received $65mg/m^2$ oxaliplatin (day 1), $135mg/m^2$ irinotecan (day 1), and $40mg/m^2$ S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue. Results In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07). Conclusion OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

  • Lu, Yan-Yan;Huang, Xin-En;Wu, Xue-Yan;Cao, Jie;Liu, Jin;Wang, Lin;Xiang, Jin
    • 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.

Incorporating Erlotinib or Irinotecan Plus Cisplatin into Chemoradiotherapy for Stage III Non-small Cell Lung Cancer According to EGFR Mutation Status

  • Lee, Youngjoo;Han, Ji-Youn;Moon, Sung Ho;Nam, Byung-Ho;Lim, Kun Young;Lee, Geon Kook;Kim, Heung Tae;Yun, Tak;An, Hye Jin;Lee, Jin Soo
    • Cancer Research and Treatment
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    • v.49 no.4
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    • pp.981-989
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    • 2017
  • Purpose Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status. Materials and Methods Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B). Patients with EGFR unknown or wild-type tumors were randomized to receive either three cycles of IP before (arm C) or after CCRT with IP (arm D). Results Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were randomized. Overall, there were seven patients in arm A, five in arm B, 22 in arm C, and 25 in arm D. The response rate was 71.4% and 80.0% for arm A and B, and 70.0% and 73.9% for arm C and D. The median overall survival (OS) was 39.3 months versus 31.2 months for arm A and B (p=0.442), and 16.3 months versus 25.3 months for arm C and D (p=0.050). Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients (74.8 months vs. 25.3 months, p=0.034). There were no unexpected toxicities. Conclusion Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC. EGFR-mutant patients appear to be a distinct subset with longer survival.