PMID- 9220320
OWN - NLM
STAT- MEDLINE
DCOM- 19970818
LR  - 20191102
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 20
IP  - 4
DP  - 1997 Jul
TI  - Phase II trial of interleukin-2 and interferon-alpha in patients with renal cell 
      carcinoma: clinical results and immunologic correlates of response.
PG  - 301-11
AB  - A phase II trial was conducted in patients with metastatic renal cell carcinoma, 
      to assess the clinical efficacy and immunoregulatory effects of 
      continuous-infusion recombinant interleukin-2 (rIL-2) (9.0 x 10(6) IU/m2/day on 
      days 1-5, 8-12, 15-19, and 22-26) and subcutaneously administered recombinant 
      human interferon-alpha 2b (rHuIFN alpha 2b) (10.0 x 10(6) U/m2/day TIW). 
      Thirty-six patients with metastatic renal cell carcinoma, performance status of 
      0-1, and measurable disease who had not received prior rIL-2, rHuIFN alpha 2b, or 
      chemotherapy were treated. Patients with CNS metastases, active infections, 
      history of another malignancy within 3 years, and those requiring corticosteroids 
      were ineligible. Cycles of rIL-2 and rHuIFN alpha 2b were administered in the 
      outpatient department every 6-8 weeks in stable or responding patients until 
      patient tolerance or a complete response were reached. Doses were modified for 
      grade III or IV toxicity. Ancillary studies included three-color immunocytometric 
      analysis of peripheral blood lymphocytes, repetitive tumor biopsies for 
      immunohistologic analysis of infiltrating cells and proliferative responses of 
      tumor infiltrating lymphocytes, and preliminary studies of changes in peripheral 
      blood T-lymphocyte signal transduction molecules [T-cell receptor (TCR)-zeta, 
      p56ick, p59fyn]. Thirty-six eligible patients were treated, with 6 of 36 patients 
      (17%, 95% confidence interval 6-33%) responding (3 complete response, 3 partial 
      response). In two of the partial responders, and in an additional three patients 
      with either minimal tumor regression (one patient) or stable disease (two 
      patients), surgical removal of residual disease was undertaken. The median 
      survival of all patients was 14 months. The toxicity of this regimen was severe, 
      but outpatient administration was possible in most instances. Immunoregulatory 
      effects on T-cell subsets included increases in various CD3+ CD25+/- HLADr+/- 
      subsets unrelated to response. Tumor biopsies before and/or during therapy were 
      obtained in 17 patients, and no consistent alterations in the degree of 
      T-lymphocyte or macrophage infiltrates could be detected. In a subset of 
      patients, tumor infiltrating lymphocyte proliferative responses and levels of 
      peripheral blood T-cell signal transduction molecules (TCR-zeta, p56lck, p59fyn) 
      were investigated. Abnormalities were found in selected patients, which improved 
      during rIL-2/rHuIFN alpha 2b therapy. This cytokine combination produces tumor 
      regression in selected patients with metastatic renal cell carcinoma. Surrogate 
      immunologic markers associated with response were not identified; however, 
      preliminary studies demonstrate investigation of immune defects and their 
      reversal with cytokine therapy is possible.
FAU - Bukowski, R M
AU  - Bukowski RM
AD  - Cancer Center Experimental Therapeutics Program, Cleveland Clinic Foundation, 
      Ohio 44195, USA.
FAU - Olencki, T
AU  - Olencki T
FAU - Wang, Q
AU  - Wang Q
FAU - Peereboom, D
AU  - Peereboom D
FAU - Budd, G T
AU  - Budd GT
FAU - Elson, P
AU  - Elson P
FAU - Sandstrom, K
AU  - Sandstrom K
FAU - Tuason, L
AU  - Tuason L
FAU - Rayman, P
AU  - Rayman P
FAU - Tubbs, R
AU  - Tubbs R
FAU - McLain, D
AU  - McLain D
FAU - Klein, E
AU  - Klein E
FAU - Novick, A
AU  - Novick A
FAU - Finke, J
AU  - Finke J
LA  - eng
GR  - P01-CA-48919/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, CD)
RN  - 0 (Interferon alpha-2)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukin-2)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, CD/analysis
MH  - Carcinoma, Renal Cell/immunology/*therapy
MH  - Female
MH  - Humans
MH  - Interferon alpha-2
MH  - Interferon-alpha/*administration & dosage/adverse effects
MH  - Interleukin-2/*administration & dosage/adverse effects
MH  - Kidney Neoplasms/immunology/*therapy
MH  - Lymphocytes, Tumor-Infiltrating/immunology
MH  - Male
MH  - Middle Aged
MH  - Recombinant Proteins
EDAT- 1997/07/01 00:00
MHDA- 1997/07/01 00:01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 1997/07/01 00:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
AID - 10.1097/00002371-199707000-00007 [doi]
PST - ppublish
SO  - J Immunother. 1997 Jul;20(4):301-11. doi: 10.1097/00002371-199707000-00007.