A phase I/II and pharmacogenomic study of pemetrexed and cisplatin in patients with unresectable, advanced gastric carcinoma
DC Field | Value | Language |
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dc.contributor.author | Chen, Jen-Shi | - |
dc.contributor.author | Chao, Yee | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.contributor.author | Roca, Enrique | - |
dc.contributor.author | Chung, Hyun C. | - |
dc.contributor.author | Palazzo, Felipe | - |
dc.contributor.author | Kim, Yeul H. | - |
dc.contributor.author | Myrand, Scott P. | - |
dc.contributor.author | Mullaney, Brian P. | - |
dc.contributor.author | Shen, Li J. | - |
dc.contributor.author | Linn, Carlos | - |
dc.date.accessioned | 2021-09-08T00:40:39Z | - |
dc.date.available | 2021-09-08T00:40:39Z | - |
dc.date.created | 2021-06-14 | - |
dc.date.issued | 2010-09 | - |
dc.identifier.issn | 0959-4973 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/115819 | - |
dc.description.abstract | 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 75mg/m(2). In phase I, the initial dose of pemetrexed was 600mg/m(2), escalated in 100mg/m(2) 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; 700mg/m(2) 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. Anti-Cancer Drugs 21: 777-784 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | - |
dc.subject | METHYLENETETRAHYDROFOLATE REDUCTASE GENE | - |
dc.subject | HIGH-DOSE METHOTREXATE | - |
dc.subject | 1ST-LINE THERAPY | - |
dc.subject | PALLIATIVE CHEMOTHERAPY | - |
dc.subject | EUROPEAN-ORGANIZATION | - |
dc.subject | COOPERATIVE GROUP | - |
dc.subject | III TRIAL | - |
dc.subject | CANCER | - |
dc.subject | FLUOROURACIL | - |
dc.subject | POLYMORPHISMS | - |
dc.title | A phase I/II and pharmacogenomic study of pemetrexed and cisplatin in patients with unresectable, advanced gastric carcinoma | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Yeul H. | - |
dc.identifier.doi | 10.1097/CAD.0b013e32833cfbca | - |
dc.identifier.scopusid | 2-s2.0-77955231880 | - |
dc.identifier.wosid | 000280448800007 | - |
dc.identifier.bibliographicCitation | ANTI-CANCER DRUGS, v.21, no.8, pp.777 - 784 | - |
dc.relation.isPartOf | ANTI-CANCER DRUGS | - |
dc.citation.title | ANTI-CANCER DRUGS | - |
dc.citation.volume | 21 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 777 | - |
dc.citation.endPage | 784 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | METHYLENETETRAHYDROFOLATE REDUCTASE GENE | - |
dc.subject.keywordPlus | HIGH-DOSE METHOTREXATE | - |
dc.subject.keywordPlus | 1ST-LINE THERAPY | - |
dc.subject.keywordPlus | PALLIATIVE CHEMOTHERAPY | - |
dc.subject.keywordPlus | EUROPEAN-ORGANIZATION | - |
dc.subject.keywordPlus | COOPERATIVE GROUP | - |
dc.subject.keywordPlus | III TRIAL | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | FLUOROURACIL | - |
dc.subject.keywordPlus | POLYMORPHISMS | - |
dc.subject.keywordAuthor | advanced gastric carcinoma | - |
dc.subject.keywordAuthor | cisplatin | - |
dc.subject.keywordAuthor | MTHFR | - |
dc.subject.keywordAuthor | pharmacogenetics | - |
dc.subject.keywordAuthor | phase I/II clinical trials | - |
dc.subject.keywordAuthor | pemetrexed | - |
dc.subject.keywordAuthor | unresectable | - |
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