PMID- 24577626
OWN - NLM
STAT- MEDLINE
DCOM- 20150904
LR  - 20211203
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 9
IP  - 4
DP  - 2014 Dec
TI  - Temsirolimus and pegylated liposomal doxorubicin (PLD) combination therapy in 
      breast, endometrial, and ovarian cancer: phase Ib results and prediction of 
      clinical outcome with FDG-PET/CT.
PG  - 339-47
LID - 10.1007/s11523-014-0309-x [doi]
AB  - Pegylated liposomal doxorubicin (PLD) is active in breast, endometrial, and 
      ovarian cancer. Preclinical data suggest that the combination of PLD with a 
      mammalian target of rapamycin (mTOR) inhibitor has an additive effect. The safety 
      and recommended phase two dose (RPTD) of temsirolimus in combination with PLD 
      were assessed. (18) F-fluorodeoxyglucose (FDG) positron emission tomography 
      (PET)/CT was performed for early response monitoring. Nineteen patients with 
      advanced breast, endometrial, and ovarian cancer were treated with increasing 
      doses of temsirolimus (10, 15, or 20 mg once weekly) and PLD (30 or 40 mg/m(2) 
      once every 4 weeks). PLD was initiated 2 weeks after start of temsirolimus. 
      FDG-PET/CT was performed at baseline, after 2 and 6 weeks. Standardized uptake 
      values (SUV), metabolic volume, and total lesion glycolysis (TLG, SUV x metabolic 
      volume) were calculated. The RPTD was 15 mg temsirolimus and 40 mg/m(2) PLD. 
      Dose-limiting toxicities (DLT) were thrombocytopenia grade 3 with nose bleeding 
      and skin toxicity grade 3. Most frequent treatment-related toxicities were 
      nausea, fatigue, mucositis, and skin toxicity. Changes in TLG after 2 weeks 
      predicted partial response (PR) after 10 weeks (p = 0.037). A rise in SUV between 
      the second and sixth week predicted progression (PD) (p = 0.034) and was 
      associated with worse progression free survival (PFS) (HR 1.068; p = 0.013). The 
      RPTD was established at 15 mg temsirolimus weekly and PLD 40 mg/m(2) once every 
      4 weeks and the combination was safe. Early response evaluation with FDG-PET/CT 
      may predict subsequent radiological PR and PD. This trial is registered under 
      number NCT0098263.
FAU - Boers-Sonderen, Marye J
AU  - Boers-Sonderen MJ
AD  - Department of Medical Oncology, Radboud UMC, PO Box 9101, 6500 HB, Nijmegen, The 
      Netherlands, marye.boers-sonderen@radboudumc.nl.
FAU - de Geus-Oei, Lioe-Fee
AU  - de Geus-Oei LF
FAU - Desar, Ingrid M E
AU  - Desar IM
FAU - van der Graaf, Winette T A
AU  - van der Graaf WT
FAU - Oyen, Wim J G
AU  - Oyen WJ
FAU - Ottevanger, Petronella B
AU  - Ottevanger PB
FAU - van Herpen, Carla M L
AU  - van Herpen CM
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140301
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (liposomal doxorubicin)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 624KN6GM2T (temsirolimus)
RN  - 80168379AG (Doxorubicin)
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  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
MH  - Breast Neoplasms/*drug therapy
MH  - Disease-Free Survival
MH  - Dose-Response Relationship, Drug
MH  - Doxorubicin/administration & dosage/*analogs & derivatives
MH  - Endometrial Neoplasms/*drug therapy
MH  - Female
MH  - Fluorodeoxyglucose F18
MH  - Glycolysis
MH  - Humans
MH  - Middle Aged
MH  - Multimodal Imaging
MH  - Ovarian Neoplasms/*drug therapy
MH  - Polyethylene Glycols/administration & dosage
MH  - Positron-Emission Tomography
MH  - Protein Kinase Inhibitors/administration & dosage
MH  - Sirolimus/administration & dosage/*analogs & derivatives
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tomography, X-Ray Computed
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2014/03/01 06:00
MHDA- 2015/09/05 06:00
CRDT- 2014/03/01 06:00
PHST- 2013/08/01 00:00 [received]
PHST- 2014/02/18 00:00 [accepted]
PHST- 2014/03/01 06:00 [entrez]
PHST- 2014/03/01 06:00 [pubmed]
PHST- 2015/09/05 06:00 [medline]
AID - 10.1007/s11523-014-0309-x [doi]
PST - ppublish
SO  - Target Oncol. 2014 Dec;9(4):339-47. doi: 10.1007/s11523-014-0309-x. Epub 2014 Mar 
      1.