Phase II study of combination chemotherapy of 5-fluorouracil, low-dose leucovorin, and oxaliplatin (FLOX regimen) in pretreated advanced gastric cancer

BACKGROUND: This phase II study describes the efficacy and safety of combination chemotherapy of 5-fluorouracil (5-FU), low-dose leucovorin, and oxaliplatin (FLOX regimen) for pretreated advanced gastric cancer. PATIENTS AND METHODS: Patients who had been previously treated with greater than or equal to one regimen were enrolled. Patients received an oxaliplatin 75 mg/m(2) on day 1, 5-FU 1000 mg/m(2) on days 1-3, and leucovorin 20 mg/m(2) on days 1-3, every 3 weeks. The primary end point was overall survival (OS). RESULTS: Among the 52 patients enrolled, 26 patients were treated as second line, and the remaining 26 patients were enrolled as third- or fourth line. A total of 203 cycles of chemotherapy were administered with the median being three cycles (range 1-15) per patient. The median OS was 6.6 months [95% confidence interval (CI) 4.5-8.8] and the median progression-free survival was 2.5 months (95% CI 1.9-3.0). The response rate was 4% (95% CI 0-9%), and the disease control rate was 48% (95% CI 34-62%). The most common toxic effects of grade 3/4 were neutropenia (16%) and vomiting (6%). CONCLUSIONS: The FLOX regimen showed modest activity as a salvage treatment in pretreated advanced gastric cancer with a favorable compliance.ope

A randomized phase 2 study of docetaxel and S-1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy

BACKGROUND: The purpose of this study was to compare 2 weekly docetaxel-based regimens as first-line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment-related clinical outcomes. METHODS: Patients were randomly selected to receive 3 weekly cycles of docetaxel (35 mg/m(2) on days 1 and 8) plus S-1 (35 mg/m(2) each twice daily on days 1-14) (DS), or docetaxel plus cisplatin (35 mg/m(2) each on days 1 and 8) (DC). Endpoints included overall response rate (primary), survival, toxicity, and quality of life (secondary). SPARC expression in prechemotherapy specimens of primary gastric tumors was evaluated via immunohistochemical analysis. RESULTS: Eighty patients were enrolled in the study. Confirmed overall response rates were 46% (95% confidence interval, 30%-62%) for DS and 24% (95% confidence interval, 11%-38%) for DC via intent-to-treat analysis. Median progression-free survival was 7.3 and 4.9 months and overall survival was 16.0 and 8.3 months for DS and DC, respectively. The most common grade ≥ 3 toxicity was neutropenia. Grade ≥ 3 mucositis (18%) and hand-foot syndrome (8%) were the toxicities most associated with DS, whereas anorexia (20%) and lethargy (20%) were more common with DC. High SPARC expression was related to early progression (hazard ratio, 3.67; P = .042) and poor overall survival (hazard ratio, 2.01; P = .010) in docetaxel chemotherapy on multivariate analysis. CONCLUSIONS: The outcomes in this study favored DS over DC for further phase 3 study. The findings suggest that split-dose weekly docetaxel alleviates hematological toxicity without compromising efficacy, and that SPARC expression may help individualize therapy in advanced gastric cancer.ope

A Case of Video-assise Thoracoscopic Pneumonectomy for Unilateral Diffuse Pulmonary Arteriovenous Malformation

Pulmonary arteriovenous malformations (PAVMs) are abnormal direct communications between the pulmonary arteries and veins. PAVMs may occur as either an isolated abnormality or in association with hereditary hemorrhagic telangiectasia, also called Osler-Weber-Rendu disease. The topic of PAVM has recently been extensively reviewed, but little is known about the clinical characteristics and course of patients having a diffuse pattern of the disease. Herein, is reported a case of unilateral diffuse PAVM in an 18 year old female patient, who underwent a right pneumonectomy, under a video-assisted thoracic surgery (VATS) approach, as the diffuse small pulmonary arteriovenous malformation involved the whole right lung.ope

Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases

BACKGROUND: The benefit of surgical resection of liver metastases from gastric cancer has not been well established. The aim of this study was to evaluate the rationale for hepatic resection in patients with hepatic metastases from gastric cancer. METHODS: Among 10 259 patients diagnosed with gastric adenocarcinoma in the Yonsei University Health System from 1995 to 2005, we reviewed the records of 58 patients with liver-only metastases from gastric cancer who underwent gastric resection regardless of hepatic surgery. RESULTS: The overall 1-year, 3-year, and 5-year survival rates of 41 patients who underwent hepatic resection with curative intent were 75.3%, 31.7%, and 20.8%, respectively, and three patients survived >7 years. Of the 41 patients, 22 had complete resection and 19 had palliative resection. Between the curative and palliative resections, survival rates after curative intent were not different. The number of liver metastasis (solitary or multiple) was a marginally significant prognostic factor for survival. CONCLUSIONS: Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if complete resection seems feasible after careful preoperative staging, even if complete resection is not actually achieved. Hepatic resection should be considered as an option for gastric cancer patients with hepatic metastases.ope

Association of the ABCB1 gene polymorphisms 2677G>T/A and 3435C>T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients

BACKGROUND: ABCB1 is responsible for multidrug resistance, the principal mechanism by which many cancers develop resistance to chemotherapeutic drugs. There is a controversy whether ABCB1 gene polymorphisms correlate with survival and response in cancer patients treated with chemotherapy. We evaluated the association between clinical outcome (safety and efficacy) of paclitaxel monotherapy in metastatic breast cancer patients with ABCB1 gene polymorphisms 2677G>T/A or 3435C>T. PATIENTS AND METHODS: Patients with metastatic breast cancer were treated with 175 mg/m(2) paclitaxel per 3-week cycle. Peripheral blood mononuclear cells from patients were used to genotype ABCB1 2677G>T/A and 3435C>T polymorphisms. Genotypes were investigated for their association with tumor response, survival, toxicity, and chemoresistance. RESULTS: ABCB1 3435 CT showed a significantly lower disease control rate than the CC genotype (P = 0.025). ABCB1 3435 CT was correlated with shorter overall survival (OS) in Cox regression analysis (P = 0.026). The 2677 GG genotype showed a significant association with chemoresistance to paclitaxel and anthracycline (P = 0.04 and 0.04, respectively). None of the ABCB1 genotypes correlated with toxicity. CONCLUSIONS: ABCB1 genotypes may be a predictor of paclitaxel activity as well as a prognostic factor in metastatic breast cancer patientsope

Docetaxel versus paclitaxel combined with 5-FU and leucovorin in advanced gastric cancer: combined analysis of two phase II trials.

PURPOSE: This is an ad hoc analysis of two phase II studies which compared the efficacy and safety of two taxanes (paclitaxel and docetaxel) combined with 5-fluorouracil (5-FU) and leucovorin (LV) in advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric adenocarcinoma who were untreated or had only received first-line chemotherapy, were treated with either paclitaxel (PFL; 175 mg/m(2)) or docetaxel (DFL; 75 mg/m(2)) on day 1, followed by a bolus of LV (20 mg/m(2) days 1~3) and a 24-hour infusion of 5-FU (1,000 mg/m(2) days 1~3) every 3 weeks. The primary endpoint was overall response rate (ORR) and the secondary endpoint included survival and toxicity. RESULTS: Sixty-six patients received DFL (first-line [n=38]; and second-line [n=28]) and 60 patients received PFL (first-line [n=37]; and second-line [n=23]). The ORRs were not significantly different between the 2 groups (DFL, 26%; PFL, 38%). With a median follow-up of 9.5 months, the progression free survival was 5.2 months (95% confidence interval [CI], 4.2~6.5 months) for DFL and 3.3 months (95% CI, 1.3~5.5 months) for PFL (p=0.17). The overall survival was also comparable between the patients who received DFL and PFL (10.0 months [95% CI, 7.2~12.5 months] and 13.9 months [95% CI, 10.9~19.2 months], respectively; p=0.37). The most frequent grade 3~4 adverse event was neutropenia (DFL, 71%; PFL, 62%). DFL and PFL had different non-hematologic toxicities; specifically, grade >or=3 mucositis (5%) and diarrhea (3%) were common in DFL, while nausea/vomiting (15%) and peripheral neuropathy (5%) were common in PFL. CONCLUSION: Thus, the two taxanes had similar efficacy in the treatment of advanced gastric cancer, but different toxicity profiles. Prospective comparative studies are required to further clarify the role of taxanes in the treatment of advanced gastric cancerope

(A)Study on the discharge characteristics by the change of the resolution & improvement in luminous efficacy of the fine discharge cell

학위논문(석사)--서울대학교 대학원 :전기·컴퓨터공학부,2007.Maste

(A) phase II study of paclitaxel combined with infusional 5-fluorouracil and low-dose l

의학과/석사[한글]진행성 위암에서 표준 항암약물 병용 요법제제는 아직 확립되어 있지 않다. 본 2 상 연구에서는 진행성 위암을 대상으로 paclitaxel과 지속 점적 주입법의 5-fluorouracil과 저용량 leucovorin 병용 용법의 효능과 안전성을 조사하였다.환자들은 175 mg/m2의 paclitaxel을 3시간 동안 정맥주입 받은 후 leucovorin 20 mg/m2과 24시간 지속 점적 주입 5-fluorouracil 1000 mg/m2을 3 일간 투여 받았다. 항암 약물치료는 3주 간격으로 시행하였고 환자의 치료거부나 수용하지 못할 이상반응, 질병의 진행이 관찰되지 않는 한 12 주기까지 시행하였다. 본 연구의 일차목적은 진행 정지 기간이었으며, 종양의 반응평가는 Response Evaluation Criteria In Solid Tumor 기준을 따랐고 안전성은 National Cancer Institute Common Toxicity Criteria 에 따라 평가하였다.총 60 명의 환자가 등록되었으며 투여 약제의 상대용량강도는 0.91 (범위, 0.64-1.00) 이었다. 진행 정지 기간은 중앙값 13.1 주 (95% 범위, 4.7 – 21.5 주) 이었고 평가가 가능한 56 명에서의 반응률은 31.7%이었으며 반응 지속 기간은 28.3 주 (95% 범위, 4.7 – 72.9 주) 이었다. 이전 항암 약물요법 유무에 따른 진행 정지 기간은 항암 약물요법을 받은 적이 없던 군에서 19.7 주 (95% 범위, 10.5 – 28.9 주), 이전에 항암 약물요법을 받은 경우는 10.7 주 (95% 범위, 7.0 – 14.4 주)이었다. 환자의 전체 생존 기간은 60.1 주 (95% 범위, 43.5 – 76.8 주)로 1년 생존율은 45% 이었다. 가장 흔한 3 – 4 등급의 부작용은 호중구 감소증이었으며 61.7%의 환자에서 나타났고, 비 혈액학적 부작용은 경미하였다.결론적으로 본 연구에서 시행한 paclitaxel, 5-FU, leucovorin의 병용요법은 기존의 병용요법과 유사한 효능을 보이며 환자들의 치료 순응도가 높고 혈액학적 부작용이 적어 진행성 위암 치료에서선택 가능한 하나의 항암 병용요법제제로 고려할 수 있다. [영문]Background.The standard chemotherapy regimen for advanced gastric cancer has not yet been established. We investigated the efficacy and safety of the combination of paclitaxel with infusional 5-fluorouracil and leucovorin in advanced gastric cancer patients .Method. Patients received paclitaxel 175 mg/m2 (3-hour infusion) followed by a leucovorin bolus 20 mg/m2 and a 24-hour infusion of 5-FU 1,000 mg/m2 (day 1–3) every 3 weeks. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) and the toxicity was evaluated by National Cancer Institute common toxicity criteria (NCI-CTC).Results. Sixty patients were enrolled and 56 patients were evaluable. Median relative dose intensity was 91%. Time to progression was 13.1 weeks (4.7 – 21.5 ) in total patiens and 19.7 weeks (10.1 – 29.3) in chemonaive patients, 12.9 weeks (1.7 – 24.1) in the 1st line group who had history of adjuvant chemotherapy and 11.7 weeks (7.9 – 15.5) in the 2nd line group. Overall survival duration was 60.1 weeks (43.5 – 76.8). Among 56 evaluable patients, the overall response rate was 31.7%. and the response duration was 28.3 weeks (4.7 – 72.9), including 6% of complete response and 32.0% of partial response. The most common grade 3-4 toxicity was neutropenia with 3.4% of febrile neutropenia. Mild to moderate non-hematologic toxicities were all self limited. Necessity of phase III study was suggested.Conclusion.The 5-FU, leucovorin, paclitaxel combination regimen showed a comparable efficacy and tolerable compliance with other second generation regimens.ope