title: Retrospective study of carmustine or lomustine with bevacizumab in recurrent glioblastoma patients who have failed prior bevacizumab.
abstract: BACKGROUND
  Currently, there are no known effective treatments for recurrent glioblastoma once patients have progressed on a bevacizumab-containing regimen. We examined the efficacy of adding nitrosoureas to bevacizumab in patients who progressed while on an initial bevacizumab-containing regimen.
  
  
  METHODS
  In this retrospective study, we identified adult patients with histologically confirmed glioblastoma (WHO grade IV) who were treated with lomustine or carmustine in combination with bevacizumab as a second or third regimen after failing an alternative initial bevacizumab-containing regimen. Response rate (RR), 6-month progression free survival (PFS6), and progression-free survival (PFS) were assessed for each treatment.
  
  
  RESULTS
  Forty-two patients were identified (28 males) with a median age of 49 years (range, 24-78 y). Of 42 patients, 28 received lomustine (n = 22) or carmustine (n = 6) with bevacizumab as their second bevacizumab-containing regimen, and 14 received lomustine (n = 11) or carmustine (n = 3) as their third bevacizumab-containing regimen. While the median PFS for the initial bevacizumab-containing regimen was 16.3 weeks, the median PFS for the nitrosourea-containing bevacizumab regimen was 6.3 weeks. Patients had an RR of 44% and a PFS6 rate of 26% during the initial bevacizumab regimen and an RR of 0% and a PFS6 rate of 3% during the nitrosourea-containing bevacizumab regimen. There was increased grade 3-4 toxicity (45% vs 19%, P = .010) during the nitrosourea-containing bevacizumab regimen relative to the initial bevacizumab regimen. Median overall survival was 18.7 weeks from initiation of the nitrosourea-containing bevacizumab regimen.
  
  
  CONCLUSIONS
  The addition of lomustine or carmustine to bevacizumab after a patient has already progressed on a bevacizumab-containing regimen does not appear to provide benefit for most patients and is associated with additional toxicity with the doses used in this cohort.
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Rifaquat
authors: R
authors: Rahman
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Kelly
authors: K
authors: Hempfling
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Andrew D
authors: AD
authors: Norden
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: David A
authors: DA
authors: Reardon
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Lakshmi
authors: L
authors: Nayak
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Mikael L
authors: ML
authors: Rinne
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Rameen
authors: R
authors: Beroukhim
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Lisa
authors: L
authors: Doherty
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Sandra
authors: S
authors: Ruland
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Arun
authors: A
authors: Rai
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Jennifer
authors: J
authors: Rifenburg
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Debra
authors: D
authors: LaFrankie
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Brian M
authors: BM
authors: Alexander
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Raymond Y
authors: RY
authors: Huang
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Patrick Y
authors: PY
authors: Wen
authors: Harvard Medical School, Boston, Massachusetts (R.R., A.D.N., D.A.R., L.N., M.L.R., R.B., B.M.A., R.Y.H., P.Y.W., E.Q.L.); Center of Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (K.H., A.D.N., D.A.R., L.N., M.L.R., R.B., L.D., S.R., J.R., D.L., P.Y.W., E.Q.L.); Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts (A.D.N., D.A.R., L.N., M.L.R., R.B., P.Y.W., E.Q.L.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (B.M.A.); Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts (R.Y.H.); Boston University School of Medicine, Boston, Massachusetts (A.R.).
authors: Eudocia Q
authors: EQ
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002330:Carmustine / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D008130:Lomustine; D002330:Carmustine
keywords: bevacizumab; malignant glioma; nitrosoureas; recurrent glioblastoma