0 327

Cited 24 times in

A Phase II Trial of Tipifarnib for Patients with Previously Treated, Metastatic Urothelial Carcinoma Harboring HRAS Mutations

Authors
 Hye Won Lee  ;  Jason K Sa  ;  Antonio Gualberto  ;  Catherine Scholz  ;  Hyun Hwan Sung  ;  Byong Chang Jeong  ;  Han Yong Choi  ;  Ghee Young Kwon  ;  Se Hoon Park 
Citation
 CLINICAL CANCER RESEARCH, Vol.26(19) : 5113-5119, 2020-10 
Journal Title
CLINICAL CANCER RESEARCH
ISSN
 1078-0432 
Issue Date
2020-10
MeSH
AMP-Activated Protein Kinase Kinases ; Aged ; Carcinoma / drug therapy* ; Carcinoma / genetics ; Carcinoma / pathology ; Drug-Related Side Effects and Adverse Reactions / classification ; Drug-Related Side Effects and Adverse Reactions / pathology ; Female ; Humans ; Male ; Middle Aged ; Mutation / genetics ; Neoplasm Metastasis ; Progression-Free Survival ; Protein Serine-Threonine Kinases / genetics* ; Proto-Oncogene Proteins p21(ras) / genetics* ; Quinolones / administration & dosage* ; Quinolones / adverse effects ; Urothelium / drug effects* ; Urothelium / metabolism ; Urothelium / pathology
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.
Full Text
https://aacrjournals.org/clincancerres/article/26/19/5113/82681/A-Phase-II-Trial-of-Tipifarnib-for-Patients-with
DOI
10.1158/1078-0432.CCR-20-1246
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Hospital Medicine (입원의학과) > 1. Journal Papers
Yonsei Authors
Lee, Hye Won(이혜원)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189966
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links