PMID- 24187608
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211021
IS  - 1948-7894 (Print)
IS  - 1948-7908 (Electronic)
IS  - 1948-7908 (Linking)
VI  - 2
IP  - 3
DP  - 2013 Sep 1
TI  - CONCURRENT WHOLE BRAIN RADIOTHERAPY AND SHORT-COURSE CHLOROQUINE IN PATIENTS WITH 
      BRAIN METASTASES: A PILOT TRIAL.
LID - 10.1007/s13566-013-0111-x [doi]
AB  - OBJECTIVE: The immune modulatory drug chloroquine (CQ) has been demonstrated to 
      enhance survival following radiotherapy in patients with high-grade glioma in a 
      clinical trial, but the efficacy in patients with brain metastases is unknown. We 
      hypothesized that short-course CQ during whole brain radiotherapy (WBRT) would 
      improve response to local therapy in patients with brain metastases. METHODS: A 
      prospective, single-cohort study was performed combining WBRT with concurrent CQ 
      to assess both the feasibility of and intracranial response to combined therapy 
      in patients with brain metastases. Safety, tolerability and overall survival of 
      this combination was also examined, along with allelic status of IDO2 
      (indoleamine 2,3-dioxygenase 2), an immune modulatory enzyme inhibited by 
      chloroquine that may affect survival outcomes. CQ therapy (250 mg by mouth daily) 
      was initiated 1 week before WBRT (37.5 Gy in 2.5 Gy daily fractions) in patients 
      with newly diagnosed brain metastases from biopsy-proven, primary lung, breast or 
      ovarian solid tumors (n=20). The primary endpoint was radiologic response 3 
      months after combined CQ and WBRT therapy. Secondary endpoints included toxicity 
      and overall survival. Patients were stratified by IDO2 allelic status. RESULTS: 
      After a median clinical follow up of 5 months (range, 0.5-31), 16 patients were 
      evaluable for radiologic response which was complete response in two patients, 
      partial response in 13 patients and stable disease in one patient. There were no 
      treatment-related grade>/=3 toxicities or treatment interruption due to toxicity. 
      Median and mean overall survival was 5.7 and 8.9 months, respectively (range, 
      0.8-31). A trend toward increased overall survival was observed in patients with 
      wild-type IDO2 compared to patients with heterozygous or homozygous 
      configurations that ablate IDO2 enzyme activity (10.4 mos vs. 4.1 mos.; p=0.07). 
      CONCLUSIONS: WBRT with concurrent, short-course CQ is well tolerated in patients 
      with brain metastases. The high intracranial disease control rate warrants 
      additional study.
FAU - Eldredge, Harriet Belding
AU  - Eldredge HB
AD  - Department of Radiation Oncology, Lankenau Medical Center, Wynnewood PA 19096 USA 
      [H.E., A.D.]; Lankenau Institute for Medical Research, Wynnewood PA 19096 USA 
      [A.D., J.B.D., M.C., G.C.P.]; New Link Genetics Corporation, Ames IA 50010 USA 
      [R.M.]; and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 
      19107 USA [H.B.E., G.C.P.].
FAU - Denittis, Albert
AU  - Denittis A
FAU - Duhadaway, James B
AU  - Duhadaway JB
FAU - Chernick, Michael
AU  - Chernick M
FAU - Metz, Richard
AU  - Metz R
FAU - Prendergast, George C
AU  - Prendergast GC
LA  - eng
GR  - R01 CA109542/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - Germany
TA  - J Radiat Oncol
JT  - Journal of radiation oncology
JID - 101590774
PMC - PMC3810973
MID - NIHMS516302
OTO - NOTNLM
OT  - 3-dioxygenase (IDO)
OT  - Whole brain radiotherapy
OT  - brain metastases
OT  - chloroquine
OT  - immunomodulation
OT  - immunotherapy
OT  - indoleamine 2
OT  - non-small cell lung cancer (NSCLC)
COIS- Conflict of interest Statement George C. Prendergast reports a conflict of 
      interest as an inventor and a compensated scientific advisor, grant recipient and 
      shareholder in New Link Genetics Corporation, which has licensed IDO2 technology 
      patented by the Lankenau Institute for Medical Research. James B. DuHadaway and 
      Richard Metz report related conflicts as inventors and shareholders in New Link 
      Genetics Corporation. Harriett Belding Eldredge, Albert DeNittis and Michael 
      Chernick declare that they have no conflict of interest.
EDAT- 2013/11/05 06:00
MHDA- 2013/11/05 06:01
PMCR- 2014/09/01
CRDT- 2013/11/05 06:00
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2013/11/05 06:01 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.1007/s13566-013-0111-x [doi]
PST - ppublish
SO  - J Radiat Oncol. 2013 Sep 1;2(3):10.1007/s13566-013-0111-x. doi: 
      10.1007/s13566-013-0111-x.