PMID- 22706484
OWN - NLM
STAT- MEDLINE
DCOM- 20121015
LR  - 20181201
IS  - 1543-0790 (Print)
IS  - 1543-0790 (Linking)
VI  - 10
IP  - 4
DP  - 2012 Apr
TI  - Phase II study of concurrent radiation therapy, temozolomide, and bevacizumab 
      followed by bevacizumab/everolimus as first-line treatment for patients with 
      glioblastoma.
PG  - 240-6
AB  - PURPOSE: To evaluate the efficacy of adding bevacizumab, a vascular endothelial 
      growth factor (VEGF) inhibitor, and everolimus, a mammalian target of rapamycin 
      (mTOR inhibitor), to standard radiation therapy/temozolomide in the first-line 
      treatment of patients with glioblastoma. PATIENTS AND METHODS: Following surgical 
      resection or biopsy, patients with newly diagnosed glioblastoma received standard 
      radiation therapy/temozolomide plus bevacizumab 10 mg/kg intravenously (IV) every 
      2 weeks. Four weeks after the completion of radiation therapy, patients began 
      oral everolimus 10 mg daily, and continued bevacizumab every 2 weeks; therapy 
      continued until tumor progression or unacceptable toxicity. RESULTS: Sixty-eight 
      patients were treated, 82% of whom had previously undergone partial or complete 
      surgical resection. Sixty-four patients completed combined modality therapy, and 
      57 patients began maintenance therapy with bevacizumab/everolimus. Thirty-one of 
      51 patients (61%) with measurable tumor had objective responses. After a median 
      follow-up of 17 months, the median progression-free survival (PFS) was 11.3 
      months (95% confidence interval [CI], 9.3-13.1 months); median overall survival 
      was 13.9 months. Toxicity was consistent with the known toxicity profile of 
      bevacizumab; grade 3/4 toxicities during maintenance therapy related to 
      everolimus included fatigue (27%), pneumonitis (7%), and stomatitis (5%). 
      CONCLUSIONS: The use of bevacizumab and everolimus as part of first-line combined 
      modality therapy for glioblastoma was feasible and efficacious. The PFS compared 
      favorably to previous reports with standard radiation therapy/temozolomide 
      therapy, and is similar to results achieved in other phase II trials in which 
      bevacizumab was added to fist-line treatment. Ongoing randomized phase III trials 
      will clarify the role of bevacizumab in this setting.
FAU - Hainsworth, John D
AU  - Hainsworth JD
AD  - Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA. 
      jhainsworth@tnonc.com
FAU - Shih, Kent C
AU  - Shih KC
FAU - Shepard, Gregg C
AU  - Shepard GC
FAU - Tillinghast, Guy W
AU  - Tillinghast GW
FAU - Brinker, Brett T
AU  - Brinker BT
FAU - Spigel, David R
AU  - Spigel DR
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Adv Hematol Oncol
JT  - Clinical advances in hematology & oncology : H&O
JID - 101167661
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Immunosuppressive Agents)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
MH  - Antineoplastic Agents, Alkylating/adverse effects/*therapeutic use
MH  - Bevacizumab
MH  - Brain Neoplasms/drug therapy/radiotherapy/*therapy
MH  - Combined Modality Therapy/methods
MH  - Dacarbazine/adverse effects/*analogs & derivatives/therapeutic use
MH  - Disease-Free Survival
MH  - Everolimus
MH  - Female
MH  - Glioblastoma/drug therapy/radiotherapy/*therapy
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Sirolimus/adverse effects/*analogs & derivatives/therapeutic use
MH  - Temozolomide
MH  - Young Adult
EDAT- 2012/06/19 06:00
MHDA- 2012/10/16 06:00
CRDT- 2012/06/19 06:00
PHST- 2012/06/19 06:00 [entrez]
PHST- 2012/06/19 06:00 [pubmed]
PHST- 2012/10/16 06:00 [medline]
PST - ppublish
SO  - Clin Adv Hematol Oncol. 2012 Apr;10(4):240-6.