Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/75819
Title:
Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma.
Authors:
Donskov, F; Middleton, Mark R; Fode, K; Meldgaard, P; Mansoor, Was; Lawrance, Jeremy A L; Thatcher, Nick; Nellemann, H; Von der Maase, Hans
Abstract:
Histamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2 with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P = 0.03), a trend towards benefit in both median survival (18.3 vs 11.4 months, P = 0.07), time to PD (4.5 vs 2.2 months, P = 0.13) and clinical benefit (CR + PR + SD) (58 vs 37%, P = 0.10) in favour of IL-2/HDC, whereas the UK study was negative for all end points. Only three patients had grade 4 toxicity; however, two were fatal. A randomised phase III trial is warranted to clarify the potential role of adding histamine to IL-2 in mRCC.
Affiliation:
Department of Oncology, Aarhus University Hospital, Denmark. fd@microbiology.au.dk
Citation:
Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma. 2005, 93 (7):757-62 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
3-Oct-2005
URI:
http://hdl.handle.net/10541/75819
DOI:
10.1038/sj.bjc.6602768
PubMed ID:
16136045
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorDonskov, F-
dc.contributor.authorMiddleton, Mark R-
dc.contributor.authorFode, K-
dc.contributor.authorMeldgaard, P-
dc.contributor.authorMansoor, Was-
dc.contributor.authorLawrance, Jeremy A L-
dc.contributor.authorThatcher, Nick-
dc.contributor.authorNellemann, H-
dc.contributor.authorVon der Maase, Hans-
dc.date.accessioned2009-07-29T11:16:53Z-
dc.date.available2009-07-29T11:16:53Z-
dc.date.issued2005-10-03-
dc.identifier.citationTwo randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma. 2005, 93 (7):757-62 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid16136045-
dc.identifier.doi10.1038/sj.bjc.6602768-
dc.identifier.urihttp://hdl.handle.net/10541/75819-
dc.description.abstractHistamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2 with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P = 0.03), a trend towards benefit in both median survival (18.3 vs 11.4 months, P = 0.07), time to PD (4.5 vs 2.2 months, P = 0.13) and clinical benefit (CR + PR + SD) (58 vs 37%, P = 0.10) in favour of IL-2/HDC, whereas the UK study was negative for all end points. Only three patients had grade 4 toxicity; however, two were fatal. A randomised phase III trial is warranted to clarify the potential role of adding histamine to IL-2 in mRCC.en
dc.language.isoenen
dc.subjectKidney Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshCarcinoma, Renal Cell-
dc.subject.meshFemale-
dc.subject.meshHistamine-
dc.subject.meshHumans-
dc.subject.meshInjections, Subcutaneous-
dc.subject.meshInterleukin-2-
dc.subject.meshKidney Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshOxidative Stress-
dc.subject.meshSurvival Analysis-
dc.titleTwo randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma.en
dc.typeArticleen
dc.contributor.departmentDepartment of Oncology, Aarhus University Hospital, Denmark. fd@microbiology.au.dken
dc.identifier.journalBritish Journal of Canceren
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