PMID- 7910716
OWN - NLM
STAT- MEDLINE
DCOM- 19940620
LR  - 20190904
IS  - 0277-3732 (Print)
IS  - 0277-3732 (Linking)
VI  - 17
IP  - 3
DP  - 1994 Jun
TI  - Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. 
      Evidence of a risk-benefit advantage of subcutaneous therapy.
PG  - 199-209
AB  - A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) 
      immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha 
      (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively 
      evaluated with regard to hepatic and metabolic adverse effects, and compared to 
      adverse effects previously reported upon high- or intermediate-dose intravenous 
      (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC 
      rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 
      weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice 
      weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 
      6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day 
      on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 
      consecutive weeks. These treatment regimens were well tolerated in the outpatient 
      setting; no toxic deaths occurred, and none of the patients developed 
      life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we 
      observed mild decreases in plasma protein and albumin levels (mean nadir +/- 
      standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor 
      albeit significant increases in serum total bilirubin levels (mean peak +/- 
      standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 
      +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase 
      (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl 
      transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 
      mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard 
      deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) 
      decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side 
      effects and laboratory changes were in marked contrast to a multitude of 
      dose-limiting and life-threatening adverse reactions described upon IV rIL-2 
      therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha 
      combination therapy as used in this study, can be given in the outpatient setting 
      with good practicability and excellent safety.
FAU - Schomburg, A
AU  - Schomburg A
AD  - Department of Hematology and Oncology, MHH University Medical Center Hannover, 
      Germany.
FAU - Kirchner, H
AU  - Kirchner H
FAU - Lopez-Hanninen, E
AU  - Lopez-Hanninen E
FAU - Menzel, T
AU  - Menzel T
FAU - Rudolph, P
AU  - Rudolph P
FAU - Korfer, A
AU  - Korfer A
FAU - Fenner, M
AU  - Fenner M
FAU - Poliwoda, H
AU  - Poliwoda H
FAU - Atzpodien, J
AU  - Atzpodien J
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PL  - United States
TA  - Am J Clin Oncol
JT  - American journal of clinical oncology
JID - 8207754
RN  - 0 (Blood Proteins)
RN  - 0 (Interferon Type I)
RN  - 0 (Interleukin-2)
RN  - 0 (Lipids)
RN  - 0 (Recombinant Proteins)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.3.2.2 (gamma-Glutamyltransferase)
RN  - EC 2.6.1.- (Transaminases)
RN  - EC 3.1.1.8 (Cholinesterases)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Alkaline Phosphatase/blood
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse 
      effects/therapeutic use
MH  - Bilirubin/blood
MH  - Blood Proteins/*drug effects
MH  - Capillary Permeability/*drug effects
MH  - Cholinesterases/blood
MH  - Clinical Enzyme Tests
MH  - Clinical Trials as Topic
MH  - Cohort Studies
MH  - Humans
MH  - Immunotherapy
MH  - Injections, Subcutaneous
MH  - Interferon Type I/administration & dosage/*adverse effects
MH  - Interleukin-2/administration & dosage/*adverse effects
MH  - L-Lactate Dehydrogenase/blood
MH  - Lipids/blood
MH  - Liver/*drug effects/enzymology
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/metabolism/*therapy
MH  - Outpatients
MH  - Recombinant Proteins/administration & dosage/adverse effects
MH  - Transaminases/blood
MH  - gamma-Glutamyltransferase/blood
EDAT- 1994/06/01 00:00
MHDA- 1994/06/01 00:01
CRDT- 1994/06/01 00:00
PHST- 1994/06/01 00:00 [pubmed]
PHST- 1994/06/01 00:01 [medline]
PHST- 1994/06/01 00:00 [entrez]
AID - 10.1097/00000421-199406000-00004 [doi]
PST - ppublish
SO  - Am J Clin Oncol. 1994 Jun;17(3):199-209. doi: 10.1097/00000421-199406000-00004.