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RISS 인기검색어
- 검색키워드
- 저자 : Myrand, Scott P. (검색결과 1 건)
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Chen, Jen-Shi,Chao, Yee,Bang, Yung-Jue,Roca, Enrique,Chung, Hyun C.,Palazzo, Felipe,Kim, Yeul H.,Myrand, Scott P.,Mullaney, Brian P.,Shen, Li J.,Linn, Carlos Lippincott Williams Wilkins, Inc. 2010 ANTICANCER DRUGS Vol.21 No.8
This phase I/II study was conducted to determine the maximum recommended dose of pemetrexed when given in combination with a fixed dose of cisplatin, and the efficacy, toxicity and association of 5,10-methylenetetrahydrofolate reductase (MTHFR) variants with this pemetrexed--cisplatin combination, in patients with unresectable, advanced gastric carcinoma. Patients 18–70 years of age, with stage IV disease or post-surgery recurrence, no earlier palliative chemotherapy, 0 or 1 Eastern Cooperative Oncology Group performance status, were included. The cisplatin dose was 75 mg/m. In phase I, the initial dose of pemetrexed was 600 mg/m, escalated in 100 mg/m increments. In phase II, efficacy, including overall response rate, overall survival, as well as toxicity and MTHFR pharmacogenetics were investigated. Phase I enrolled 16 patients; 700 mg/m was defined as pemetrexed recommended dose. Thirteen serious adverse events were reported; the most common grade 3/4 toxicities were haematologic (10 of 13, 76.9%). Phase II enrolled 73 patients, 69 qualified for safety and 68 for efficacy analysis; 65 for pharmacogenomic analysis. Overall response rate was 23.5% (14.1%, 35.4%), disease control rate 55.9%, median overall survival 11.8 months (95% confidence interval, 7.2–18.5 months), progression-free survival 4.9 months (95% confidence interval, 2.8–7.1 months), and median response duration 5.4 months. Patients with MTHFR A1298C variants had median overall survival of 6.6 months, significantly shorter than patients with the wild type (median 18.5 months, P=0.001). The pemetrexed--cisplatin combination in patients with advanced gastric cancer generates modest efficacy and a manageable toxicity profile. The reduced overall survival in patients with MTHFR A1298C polymorphism variants deserves further investigation.
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