PMID- 19636010
OWN - NLM
STAT- MEDLINE
DCOM- 20090925
LR  - 20210102
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 27
IP  - 26
DP  - 2009 Sep 10
TI  - Phase I study of the humanized anti-CD40 monoclonal antibody dacetuzumab in 
      refractory or recurrent non-Hodgkin's lymphoma.
PG  - 4371-7
LID - 10.1200/JCO.2008.21.3017 [doi]
AB  - PURPOSE: To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics, 
      and antitumor activity of dacetuzumab in patients with refractory or recurrent 
      B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: In this open-label, 
      dose-escalation phase I study, dacetuzumab was administered to six cohorts of 
      adult patients. In the first cohort, patients received 2 mg/kg weekly for 4 
      weeks; in all other cohorts, an intrapatient dose-escalation schedule was used 
      with increasing doses up to a maximum of 8 mg/kg. Patients with clinical benefit 
      after one cycle of dacetuzumab were eligible for a second cycle. RESULTS: In the 
      50 patients who received dacetuzumab, no dose dependence of adverse events (AEs) 
      was observed. The most common AEs in >or= 20% of patients were fatigue, pyrexia, 
      and headache; most were grade 1 or 2. Noninfectious inflammatory eye disorders 
      occurred in 12% of patients. AEs grade >or= 3 occurred in 30% of patients and 
      included disease progression, anemia, pleural effusion, and thrombocytopenia. 
      Most laboratory abnormalities were grade 1 or 2; transient elevated hepatic 
      aminotransferases occurred in 52% of patients. Two patients experienced 
      dose-limiting toxicity: grade 3 conjunctivitis and transient vision loss in 
      cohort (1), and grade 3 ALT elevation in cohort IV. The MTD of dacetuzumab was 
      not established at the dose levels tested. Six objective responses were reported 
      (one complete response, five partial responses). Tumor size decreased in 
      approximately one third of patients. CONCLUSION: Dacetuzumab monotherapy was well 
      tolerated in patients with NHL in doses up to 8 mg/kg/wk. Preliminary response 
      data are encouraging and support additional studies of dacetuzumab in this 
      patient population.
FAU - Advani, Ranjana
AU  - Advani R
AD  - Division of Oncology, Stanford University Medical Center, 875 Blake Wilbur Dr, 
      Stanford, CA 94305, USA. radvani@stanford.edu
FAU - Forero-Torres, Andres
AU  - Forero-Torres A
FAU - Furman, Richard R
AU  - Furman RR
FAU - Rosenblatt, Joseph D
AU  - Rosenblatt JD
FAU - Younes, Anas
AU  - Younes A
FAU - Ren, Hong
AU  - Ren H
FAU - Harrop, Kate
AU  - Harrop K
FAU - Whiting, Nancy
AU  - Whiting N
FAU - Drachman, Jonathan G
AU  - Drachman JG
LA  - eng
SI  - ClinicalTrials.gov/NCT00103779
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20090727
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (CD40 Antigens)
RN  - 0 (Cytokines)
RN  - UT59FF4T5X (dacetuzumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia/chemically induced
MH  - Antibodies, Monoclonal/adverse effects/pharmacokinetics/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - CD40 Antigens/*immunology
MH  - Cohort Studies
MH  - Cytokines/blood
MH  - Dose-Response Relationship, Drug
MH  - Drug Resistance, Neoplasm
MH  - Fatigue/chemically induced
MH  - Female
MH  - Fever/chemically induced
MH  - Headache/chemically induced
MH  - Humans
MH  - Lymphoma, B-Cell/drug therapy/metabolism
MH  - Lymphoma, Non-Hodgkin/*drug therapy/metabolism
MH  - Male
MH  - Middle Aged
MH  - Recurrence
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2009/07/29 09:00
MHDA- 2009/09/26 06:00
CRDT- 2009/07/29 09:00
PHST- 2009/07/29 09:00 [entrez]
PHST- 2009/07/29 09:00 [pubmed]
PHST- 2009/09/26 06:00 [medline]
AID - JCO.2008.21.3017 [pii]
AID - 10.1200/JCO.2008.21.3017 [doi]
PST - ppublish
SO  - J Clin Oncol. 2009 Sep 10;27(26):4371-7. doi: 10.1200/JCO.2008.21.3017. Epub 2009 
      Jul 27.