Cited 29 times in
A Phase II Trial of Tipifarnib for Patients with Previously Treated, Metastatic Urothelial Carcinoma Harboring HRAS Mutations
DC Field | Value | Language |
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dc.contributor.author | 이혜원 | - |
dc.date.accessioned | 2022-09-02T01:07:15Z | - |
dc.date.available | 2022-09-02T01:07:15Z | - |
dc.date.issued | 2020-10 | - |
dc.identifier.issn | 1078-0432 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/189966 | - |
dc.description.abstract | Purpose: To assess the antitumor activity and safety of tipifarnib, a highly potent and selective farnesyltransferase inhibitor, we performed a phase II clinical trial in patients with advanced and refractory urothelial carcinoma harboring missense HRAS mutations. Patients and Methods: A total of 245 adult patients with previously treated, advanced urothelial carcinoma entered the molecular screening program including HRAS. Those with missense HRAS mutations or STK11:rs2075606 received oral tipifarnib 900 mg twice daily on days 1-7 and 15-21 of 28-day treatment cycles. The primary endpoint was progression-free survival at 6 months (PFS6). Results: Weidentified 16 (7%) missense HRASmutations (G13R, 7; Q61R, 4; G12S, 3; G12C, 2) and 104 (46%) STK11:rs2075606 carriers. In 21 patients enrolled in the study, 14 and 7 patients had missense HRAS mutations and STK11:rs2075606, respectively. The most frequently observed adverse events included fatigue (86%) and hematologic toxicities. With a median follow-up of 28 months, 4 patients (19%) reached PFS6: 3 had missense HRAS mutations and one patient, enrolled as an STK11 carrier, had HRAS frameshift insertions at H27fs and H28fs rendering a nonsense HRAS mutation. The overall response rate by intent-totreat analysis was 24% (4 missense and one nonsense frameshift HRAS mutation); no response was observed in patients with urothelial carcinoma with wild- type HRAS tumors. Five responses were observed in 12 evaluable patients of 15 with tumors carrying HRAS mutations. Conclusions: Oral tipifarnib resulted in a manageable safety profile and encouraging antitumor efficacy against treatmentrefractory urothelial carcinoma containing HRAS mutations. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | CLINICAL CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | AMP-Activated Protein Kinase Kinases | - |
dc.subject.MESH | Aged | - |
dc.subject.MESH | Carcinoma / drug therapy* | - |
dc.subject.MESH | Carcinoma / genetics | - |
dc.subject.MESH | Carcinoma / pathology | - |
dc.subject.MESH | Drug-Related Side Effects and Adverse Reactions / classification | - |
dc.subject.MESH | Drug-Related Side Effects and Adverse Reactions / pathology | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Mutation / genetics | - |
dc.subject.MESH | Neoplasm Metastasis | - |
dc.subject.MESH | Progression-Free Survival | - |
dc.subject.MESH | Protein Serine-Threonine Kinases / genetics* | - |
dc.subject.MESH | Proto-Oncogene Proteins p21(ras) / genetics* | - |
dc.subject.MESH | Quinolones / administration & dosage* | - |
dc.subject.MESH | Quinolones / adverse effects | - |
dc.subject.MESH | Urothelium / drug effects* | - |
dc.subject.MESH | Urothelium / metabolism | - |
dc.subject.MESH | Urothelium / pathology | - |
dc.title | A Phase II Trial of Tipifarnib for Patients with Previously Treated, Metastatic Urothelial Carcinoma Harboring HRAS Mutations | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Hospital Medicine (입원의학과) | - |
dc.contributor.googleauthor | Hye Won Lee | - |
dc.contributor.googleauthor | Jason K Sa | - |
dc.contributor.googleauthor | Antonio Gualberto | - |
dc.contributor.googleauthor | Catherine Scholz | - |
dc.contributor.googleauthor | Hyun Hwan Sung | - |
dc.contributor.googleauthor | Byong Chang Jeong | - |
dc.contributor.googleauthor | Han Yong Choi | - |
dc.contributor.googleauthor | Ghee Young Kwon | - |
dc.contributor.googleauthor | Se Hoon Park | - |
dc.identifier.doi | 10.1158/1078-0432.CCR-20-1246 | - |
dc.contributor.localId | A05913 | - |
dc.relation.journalcode | J00564 | - |
dc.identifier.pmid | 32636318 | - |
dc.identifier.url | https://aacrjournals.org/clincancerres/article/26/19/5113/82681/A-Phase-II-Trial-of-Tipifarnib-for-Patients-with | - |
dc.contributor.alternativeName | Lee, Hye Won | - |
dc.contributor.affiliatedAuthor | 이혜원 | - |
dc.citation.volume | 26 | - |
dc.citation.number | 19 | - |
dc.citation.startPage | 5113 | - |
dc.citation.endPage | 5119 | - |
dc.identifier.bibliographicCitation | CLINICAL CANCER RESEARCH, Vol.26(19) : 5113-5119, 2020-10 | - |
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