title: A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas.
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.
  
  
  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.
  
  
  CONCLUSIONS
  The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN.
authors: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul.
authors: S J
authors: SJ
authors: Kim
authors: Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul.
authors: D-Y
authors: DY
authors: Shin
authors: Department of Internal Medicine, Yonsei University College of Medicine, Seoul.
authors: J S
authors: JS
authors: Kim
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: D H
authors: DH
authors: Yoon
authors: Department of Internal Medicine, Inje University College of Medicine, Inje University Busan Paik Hospital, Gaegumdong, Busanjingu, Busan, Republic of Korea.
authors: W S
authors: WS
authors: Lee
authors: Hematology-Oncology Clinic, National Cancer Center, Goyang-city.
authors: H
authors: H
authors: Lee
authors: Department of Hematology-Oncology, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu.
authors: Y R
authors: YR
authors: Do
authors: Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul.
authors: H J
authors: HJ
authors: Kang
authors: Hematology-Oncology Clinic, National Cancer Center, Goyang-city.
authors: H S
authors: HS
authors: Eom
authors: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
authors: Y H
authors: YH
authors: Ko
authors: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul.
authors: S H
authors: SH
authors: Lee
authors: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul Samsung Biomedical Research Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul.
authors: H Y
authors: HY
authors: Yoo
authors: Department of Pathology, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
authors: M
authors: M
authors: Hong
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: C
authors: C
authors: Suh
authors: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul wskimsmc@skku.edu.
authors: W S
authors: WS
authors: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D000068338:Everolimus / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D011241:Prednisone
keywords: CHOP; T-cell lymphoma; everolimus