PMID- 19140204
OWN - NLM
STAT- MEDLINE
DCOM- 20090324
LR  - 20210102
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 115
IP  - 4
DP  - 2009 Feb 15
TI  - A phase 2, randomized study of SB-485232, rhIL-18, in patients with previously 
      untreated metastatic melanoma.
PG  - 859-68
LID - 10.1002/cncr.24100 [doi]
AB  - BACKGROUND: Phase 1 studies demonstrated evidence of recombinant human IL-18 
      (rhIL-18)-mediated immunomodulatory and clinical activity, and defined a 
      biologically active dose range. METHODS: A phase 2 study of rhIL-18 was conducted 
      in untreated AJCC stage IV melanoma. Patients were randomized to 1 of 3 dose 
      groups (0.01, 0.1, and 1.0 mg/kg/d) of rhIL-18 administered as 5 daily 
      intravenous infusions repeated every 28 days. A 2-stage design with a stopping 
      rule was used. RESULTS: A total of 64 patients (median age, 57.5 years) with 
      metastatic melanoma (M1a/b (30), M1c (34)) were accrued to stage I, and 
      randomized to 3 groups (21 [0.01 mg/kg/d], 21 [0.1 mg/kg/d], 22 [1.0 mg/kg/d]). 
      Five patients experienced 10 grade 3 drug-related adverse events (AEs): 
      polyarthritis (1 subject: 0.01 mg/kg); deep vein thrombosis, pulmonary embolism 
      (1:0.01 mg/kg); cognitive disorder (1:0.1 mg/kg); fatigue, dyspnea, pleural 
      effusion, lymphopenia (1:1.0 mg/kg); fatigue, lymphopenia (1:1.0 mg/kg). One 
      patient experienced a grade 4 AE of increased lipase (0.1 mg/kg) that led to 
      permanent discontinuation from the study. Among 63 subjects evaluable for 
      response, 1 (M1c; 0.01 mg/kg) achieved a partial response after 4 cycles. Four 
      subjects (3 at 0.01 mg/kg and 1 at 1.0 mg/kg) had stable disease maintained for 6 
      months or longer. Due to the low apparent level of clinical efficacy using RECIST 
      criteria, the study was terminated at the end of stage 1. The median progression 
      free survival for the 3 groups was 7.5 (0.01), 7.4 (0.1), and 7.3 (1.0) weeks. 
      CONCLUSIONS: rIL-18 as tested in this trial was well tolerated, but had limited 
      activity as a single agent in patients with metastatic melanoma.
CI  - (c) 2009 American Cancer Society.
FAU - Tarhini, Ahmad A
AU  - Tarhini AA
AD  - Department of Medicine, Division of Hematology/Oncology, University of 
      Pittsburgh, Melanoma and Skin Cancer Program, University of Pittsburgh Cancer 
      Institute, Pittsburgh, Pennsylvania 15213-2584, USA.
FAU - Millward, Michael
AU  - Millward M
FAU - Mainwaring, Paul
AU  - Mainwaring P
FAU - Kefford, Richard
AU  - Kefford R
FAU - Logan, Ted
AU  - Logan T
FAU - Pavlick, Anna
AU  - Pavlick A
FAU - Kathman, Steven J
AU  - Kathman SJ
FAU - Laubscher, Kevin H
AU  - Laubscher KH
FAU - Dar, Mohammed M
AU  - Dar MM
FAU - Kirkwood, John M
AU  - Kirkwood JM
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Interleukin-18)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Interleukin-18/*therapeutic use
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Melanoma/*drug therapy/secondary
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Recombinant Proteins/*therapeutic use
MH  - Risk Factors
MH  - Skin Neoplasms/*drug therapy/pathology
MH  - Treatment Outcome
EDAT- 2009/01/14 09:00
MHDA- 2009/03/25 09:00
CRDT- 2009/01/14 09:00
PHST- 2009/01/14 09:00 [entrez]
PHST- 2009/01/14 09:00 [pubmed]
PHST- 2009/03/25 09:00 [medline]
AID - 10.1002/cncr.24100 [doi]
PST - ppublish
SO  - Cancer. 2009 Feb 15;115(4):859-68. doi: 10.1002/cncr.24100.