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A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas

Authors
 S. J. Kim  ;  D.-Y. Shin  ;  J. S. Kim  ;  D. H. Yoon  ;  W. S. Lee  ;  H. Lee  ;  Y. R. Do  ;  H. J. Kang  ;  H. S. Eom  ;  Y. H. Ko  ;  S. H. Lee  ;  H. Y. Yoo  ;  M. Hong  ;  C. Suh  ;  W. S. Kim 
Citation
 ANNALS OF ONCOLOGY, Vol.27(4) : 712-718, 2016 
Journal Title
 ANNALS OF ONCOLOGY 
ISSN
 0923-7534 
Issue Date
2016
MeSH
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Cyclophosphamide/administration & dosage ; Cyclophosphamide/adverse effects ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Doxorubicin/adverse effects ; Drug Administration Schedule ; Everolimus/administration & dosage* ; Everolimus/adverse effects ; Female ; Humans ; Lymphoma, T-Cell, Peripheral/drug therapy* ; Lymphoma, T-Cell, Peripheral/pathology ; Male ; Middle Aged ; Neoplasm Staging ; PTEN Phosphohydrolase/biosynthesis ; PTEN Phosphohydrolase/genetics* ; Prednisone/administration & dosage ; Prednisone/adverse effects ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/genetics ; Treatment Outcome ; Vincristine/administration & dosage ; Vincristine/adverse effects
Keywords
CHOP ; T-cell lymphoma ; everolimus
Abstract
BACKGROUND: Everolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results. PATIENTS AND METHODS: Participants (n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response. RESULTS: The objective response rate was 90% with CR (n = 17) and PR (n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL-not-otherwise specified and ALK-negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia. CONCLUSION: The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN.
Full Text
https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdv624
DOI
10.1093/annonc/mdv624
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jin Seok(김진석) ORCID logo https://orcid.org/0000-0001-8986-8436
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152779
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