PMID- 19963099
OWN - NLM
STAT- MEDLINE
DCOM- 20100121
LR  - 20211203
IS  - 1532-8708 (Electronic)
IS  - 0093-7754 (Linking)
VI  - 36 Suppl 3
DP  - 2009 Dec
TI  - Temsirolimus in mantle cell lymphoma and other non-Hodgkin lymphoma subtypes.
PG  - S37-45
LID - 10.1053/j.seminoncol.2009.10.012 [doi]
AB  - Temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), has 
      anti-tumor activity in patients with relapsed or refractory mantle cell lymphoma 
      (MCL) and other mature lymphoid neoplasms. mTOR is an intracellular kinase that 
      controls the mRNA translation of many proteins (eg, cyclin D1) that can act as 
      oncogenes and contribute to lymphomagenesis. Characterized by overexpression of 
      cyclin D1, MCL was identified as a disease that might be susceptible to mTOR 
      inhibition. When single-agent temsirolimus was explored in two phase II studies 
      for treatment of patients with relapsed or refractory MCL, it demonstrated 
      anti-tumor activity, with overall response rates of 38% and 41%. Subsequently, a 
      three-arm, randomized phase III trial was conducted to compare two dosing 
      regimens of temsirolimus with investigator's choice of therapy for heavily 
      pretreated patients with relapsed or refractory MCL (N = 162; randomized 1:1:1). 
      Once-weekly intravenous temsirolimus 175 mg for 3 weeks followed by 75 mg once 
      weekly (175/75) significantly improved progression-free survival (hazard ratio = 
      0.44; P = .0009) versus investigator's choice therapy. Median progression-free 
      survival durations were 4.8 and 1.9 months, respectively. The objective response 
      rates were 22% in the 175/75 group and 2% in the investigator's choice group (P = 
      .0019). For patients receiving temsirolimus, the most frequent grade 3 or 4 
      adverse events were thrombocytopenia, anemia, neutropenia, and asthenia. The 
      results of this trial established a recommended clinical dose for temsirolimus 
      monotherapy in patients with relapsed or refractory MCL and validated the 
      importance of mTOR in the pathogenesis of advanced MCL. Objective responses also 
      have been reported for other mature B-cell neoplasms (eg, diffuse large B-cell 
      lymphoma or follicular lymphoma) in the phase II setting. Temsirolimus as 
      monotherapy or in combination with other active agents warrants further 
      investigation for treatment of MCL and other non-Hodgkin lymphomas.
FAU - Hess, Georg
AU  - Hess G
AD  - Department of Haematology/Oncology, Johannes Gutenberg-University, 
      Langenbeckstrasse 1, Mainz, Germany. g.hess@3-med.klinik.uni-mainz.de
FAU - Smith, Sonali M
AU  - Smith SM
FAU - Berkenblit, Anna
AU  - Berkenblit A
FAU - Coiffier, Bertrand
AU  - Coiffier B
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Semin Oncol
JT  - Seminars in oncology
JID - 0420432
RN  - 0 (Antineoplastic Agents)
RN  - 624KN6GM2T (temsirolimus)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antineoplastic Agents/administration & dosage/therapeutic use
MH  - Clinical Trials as Topic/methods
MH  - Humans
MH  - Lymphoma, Mantle-Cell/*drug therapy
MH  - Lymphoma, Non-Hodgkin/classification/*drug therapy
MH  - Models, Biological
MH  - Protein Kinases/metabolism/physiology
MH  - Sirolimus/administration & dosage/*analogs & derivatives/therapeutic use
MH  - TOR Serine-Threonine Kinases
RF  - 45
EDAT- 2010/01/09 06:00
MHDA- 2010/01/22 06:00
CRDT- 2009/12/08 06:00
PHST- 2009/12/08 06:00 [entrez]
PHST- 2010/01/09 06:00 [pubmed]
PHST- 2010/01/22 06:00 [medline]
AID - S0093-7754(09)00194-8 [pii]
AID - 10.1053/j.seminoncol.2009.10.012 [doi]
PST - ppublish
SO  - Semin Oncol. 2009 Dec;36 Suppl 3:S37-45. doi: 10.1053/j.seminoncol.2009.10.012.