Annals of Oncology 13:441-449, 2002
© 2002 European Society for Medical Oncology
Outpatient treatment with subcutaneous histamine dihydrochloride in combination with interleukin-2 and interferon-
in patients with metastatic renal cell carcinoma: results of an open single-armed multicentre phase II study
Departments of 1Oncology and 5Radiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Oncology, Umeå University Hospital, Umeå, Departments of 3Oncology and 6Virology, Sahlgrenska University Hospital, Göteborg; 4Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm; 7Umbilicus Nordica, Umeå; 8Department of Surgery, Umeå University Hospital, Umeå, Sweden
Received 27 June 2001; revised 3 September 2001; accepted 20 September 2001.
Objectives
Histamine inhibits formation and release of monocyte/macrophage-derived reactive oxygen metabolites and thereby protects natural killer (NK) and T cells against oxidative inhibition. Efficacy and safety of histamine, when given in combination with interleukin-2 (IL-2) and interferon-
(IFN-), were evaluated in patients with metastatic renal cell carcinoma (mRCC).
Patients and methods
Forty-eight mRCC patients were included. The self-administered, outpatient regimen included IFN-, 3 MIU s.c., once daily for 1 week, followed by up to nine 4 week cycles of IFN-, 3 MIU s.c., days 1–7, weeks 1–4; interleukin-2, 2.4 MIU/m2 s.c., b.i.d., days 1–5, weeks 1 and 2; and histamine dihydrochloride, 1 mg s.c., b.i.d. days 1–5, weeks 1–4.
Results
Forty-six patients were eligible. Forty-two patients were evaluable for response with four partial responses (9% of eligible patients, 10% of evaluable patients). Fifteen patients (36%) had stable disease. After subsequent surgery of residual tumours, three patients (7%) had no evidence of disease at 14+, 21+ and 21+ months. Median survival time for all patients was 16.3 months. One grade 4 toxicity (thrombocytopenia) was observed. Most frequent grade 3 toxicities were fatigue/malaise (26%), dyspnoe (11%), nausea (9%) and stomatitis (9%). Four patients discontinued due to treatment-related toxicity. There were no treatment-related deaths.
Conclusions
The present combination of histamine with IL-2 and IFN- as self-administered outpatient therapy is a safe and well-tolerated regimen. However, histamine does not appear to add efficacy with respect to response in this low-dose schedule of IL-2 and IFN-. Whether histamine might improve efficacy with higher doses of IL-2 and IFN- requires further investigation.
Key words: histamine, interferon-, interleukin-2, renal cell carcinoma
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