PMID- 18519778
OWN - NLM
STAT- MEDLINE
DCOM- 20080828
LR  - 20211120
IS  - 1078-0432 (Print)
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 11
DP  - 2008 Jun 1
TI  - A dose-escalation study of recombinant human interleukin-18 using two different 
      schedules of administration in patients with cancer.
PG  - 3462-9
LID - 10.1158/1078-0432.CCR-07-4740 [doi]
AB  - PURPOSE: Interleukin-18 (IL-18) is an immunostimulatory cytokine with antitumor 
      activity in preclinical models. A phase I study of recombinant human IL-18 
      (rhIL-18) was done to determine the toxicity, pharmacokinetics, and biological 
      activities of rhIL-18 administered at different doses in two different schedules 
      to patients with advanced cancer. EXPERIMENTAL DESIGN: Cohorts of three to four 
      patients were given escalating doses of rhIL-18 as a 2-h i.v. infusion either on 
      5 consecutive days repeated every 28 days (group A) or once a week (group B) for 
      up to 6 months. Toxicities were graded using standard criteria. Blood samples 
      were obtained for safety, pharmacokinetic, and pharmacodynamic measurements. 
      RESULTS: Nineteen patients (10 melanoma and 9 renal cell cancer) were given 
      rhIL-18 in doses of 100, 500, or 1,000 microg/kg (group A) or 100, 1,000, or 
      2,000 microg/kg (group B). Common side effects included chills, fever, headache, 
      fatigue, and nausea. Common laboratory abnormalities included transient, 
      asymptomatic grade 1 to 3 lymphopenia, grade 1 to 4 hyperglycemia, grade 1 to 2 
      anemia, neutropenia, hypoalbuminemia, liver enzyme elevations, and serum 
      creatinine elevations. No dose-limiting toxicities were observed. Biological 
      effects of rhIL-18 included transient lymphopenia and increased expression of 
      activation antigens on lymphocytes. Increases in serum concentrations of 
      IFN-gamma, granulocyte macrophage colony-stimulating factor, and IL-18-binding 
      protein were observed following dosing. CONCLUSIONS: rhIL-18 can be given in 
      biologically active doses by either weekly infusions or daily infusions for 5 
      days repeated every 28 days to patients with advanced cancer. Toxicity was 
      generally mild to moderate, and a maximum tolerated dose of rhIL-18 by either 
      schedule was not determined.
FAU - Robertson, Michael J
AU  - Robertson MJ
AD  - Lymphoma Program, Indiana University School of Medicine, 535 Barnhill Drive, 
      Indianapolis, IN 46202, USA. mjrobert@iupui.edu
FAU - Kirkwood, John M
AU  - Kirkwood JM
FAU - Logan, Theodore F
AU  - Logan TF
FAU - Koch, Kevin M
AU  - Koch KM
FAU - Kathman, Steven
AU  - Kathman S
FAU - Kirby, Lyndon C
AU  - Kirby LC
FAU - Bell, William N
AU  - Bell WN
FAU - Thurmond, Linda M
AU  - Thurmond LM
FAU - Weisenbach, Jill
AU  - Weisenbach J
FAU - Dar, Mohammed M
AU  - Dar MM
LA  - eng
GR  - M01 RR000750/RR/NCRR NIH HHS/United States
GR  - RR00750-27S3/RR/NCRR NIH HHS/United States
GR  - MO1 RR00750/RR/NCRR NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Interleukin-18)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Aged
MH  - Antibodies/blood
MH  - Antineoplastic Agents/*administration & dosage/immunology/pharmacokinetics
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Interleukin-18/*administration & dosage/immunology/pharmacokinetics
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Recombinant Proteins/*administration & dosage/immunology/pharmacokinetics
PMC - PMC8603216
MID - NIHMS1753423
COIS- Disclosure of Potential Conflicts of Interest K. Koch, L. Kirby, W. Bell, and M. 
      Dar are employed by GlaxoSmithKline. M. Robertson received a research grant from 
      GlaxoSmithKline and has a financial interest in Eli Lilly Corporation. The other 
      authors have disclosed no potential conflicts of interest.
EDAT- 2008/06/04 09:00
MHDA- 2008/08/30 09:00
PMCR- 2021/11/19
CRDT- 2008/06/04 09:00
PHST- 2008/06/04 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/06/04 09:00 [entrez]
PHST- 2021/11/19 00:00 [pmc-release]
AID - 14/11/3462 [pii]
AID - 10.1158/1078-0432.CCR-07-4740 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Jun 1;14(11):3462-9. doi: 10.1158/1078-0432.CCR-07-4740.