PMID- 24075777
OWN - NLM
STAT- MEDLINE
DCOM- 20140912
LR  - 20151119
IS  - 1938-0674 (Electronic)
IS  - 1533-0028 (Linking)
VI  - 12
IP  - 4
DP  - 2013 Dec
TI  - A phase 1B study of dulanermin in combination with modified FOLFOX6 plus 
      bevacizumab in patients with metastatic colorectal cancer.
PG  - 248-54
LID - S1533-0028(13)00071-6 [pii]
LID - 10.1016/j.clcc.2013.06.002 [doi]
AB  - OBJECTIVES: The study objectives were to evaluate the safety, tolerability, and 
      preliminary efficacy of multiple doses of dulanermin in combination with modified 
      FOLFOX6 and bevacizumab in previously untreated patients with locally advanced, 
      recurrent, or metastatic colorectal cancer. PATIENTS AND METHODS: A total of 23 
      patients received dulanermin at dosages of 4.5 or 9 mg/kg/d given on days 1 to 3 
      of each 14-day cycle along with standard dosing of modified FOLFOX6 plus 
      bevacizumab. Dose-limiting toxicities, adverse events (AEs), maximum tolerated 
      dose, and response according to Response Evaluation Criteria in Solid Tumors were 
      assessed. RESULTS: In the first cohort (3 patients given dulanermin at 4.5 
      mg/kg/d) and second cohort (6 patients given dulanermin at 9 mg/kg/day), no 
      dose-limiting toxicities were observed. The subsequent 14 patients were treated 
      with a dulanermin dosage of 9 mg/kg/d. Patients (N = 23) received 2 to 42 cycles 
      of dulanermin (median 15). The most common grade 3 or 4 AEs were neutropenia 
      (39%), hypertension (17%), peripheral neuropathy (17%), hand-foot syndrome (13%), 
      and pulmonary embolism (13%). Three patients (13%) discontinued the study because 
      of serious AEs. Overall, a best response of partial response was observed in 13 
      patients (57%) (9 confirmed, 4 unconfirmed), stable disease was observed in 7 
      patients (30%), and disease progression was observed in 3 patients (13%). The 
      median progression-free survival was 9.9 months (95% confidence interval, 
      7.0-12.7). CONCLUSIONS: Overall, the addition of dulanermin to first-line FOLFOX 
      plus bevacizumab was well tolerated in patients with advanced colorectal cancer, 
      with similar AEs that would be expected from FOLFOX plus bevacizumab. A 
      randomized study is required to assess the clinical efficacy of dulanermin in 
      this patient population.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Wainberg, Zev A
AU  - Wainberg ZA
AD  - David Geffen School of Medicine, University of California, Los Angeles, CA. 
      Electronic address: zwainberg@mednet.ucla.edu.
FAU - Messersmith, Wells A
AU  - Messersmith WA
FAU - Peddi, Parvin F
AU  - Peddi PF
FAU - Kapp, Amy V
AU  - Kapp AV
FAU - Ashkenazi, Avi
AU  - Ashkenazi A
FAU - Royer-Joo, Stephanie
AU  - Royer-Joo S
FAU - Portera, Chia C
AU  - Portera CC
FAU - Kozloff, Mark F
AU  - Kozloff MF
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20130927
PL  - United States
TA  - Clin Colorectal Cancer
JT  - Clinical colorectal cancer
JID - 101120693
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Organoplatinum Compounds)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - Folfox protocol
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Bevacizumab
MH  - Colorectal Neoplasms/*drug therapy/pathology
MH  - Disease-Free Survival
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects
MH  - Humans
MH  - Leucovorin/administration & dosage/adverse effects
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Organoplatinum Compounds/administration & dosage/adverse effects
MH  - TNF-Related Apoptosis-Inducing Ligand/*administration & dosage/adverse effects
OTO - NOTNLM
OT  - Apo2L/TRAIL
OT  - Apoptosis
OT  - Death receptor
OT  - Dulanermin
OT  - FOLFOX
OT  - Metastatic colorectal cancer
EDAT- 2013/10/01 06:00
MHDA- 2014/09/13 06:00
CRDT- 2013/10/01 06:00
PHST- 2013/04/17 00:00 [received]
PHST- 2013/06/14 00:00 [revised]
PHST- 2013/06/17 00:00 [accepted]
PHST- 2013/10/01 06:00 [entrez]
PHST- 2013/10/01 06:00 [pubmed]
PHST- 2014/09/13 06:00 [medline]
AID - S1533-0028(13)00071-6 [pii]
AID - 10.1016/j.clcc.2013.06.002 [doi]
PST - ppublish
SO  - Clin Colorectal Cancer. 2013 Dec;12(4):248-54. doi: 10.1016/j.clcc.2013.06.002. 
      Epub 2013 Sep 27.