A phase II study of interferon‐α, interleukin‐2 and 5‐fluorouracil in advanced renal carcinoma: clinical data and laboratory evidence of protease activation

Abstract

which may be a suitable target for pharmacological with responses in 24% (95% CI 10-38%) of evaluable patients and 16% of all patients. Amongst 25 evalu-intervention in attempts to ameliorate toxicity. Keywords Interleukin-2, interferon-a, 5-fluorouracil, able patients who had undergone nephrectomy, the response rate was 32% (95% CI 14-50%), whereas renal cancer, therapy, toxicity, protease, kallikrein, complement, elastase there was only one response amongst 22 patients who had not undergone nephrectomy. The median survival able by surgery alone. The observation of rare spon-

Treatment of metastatic renal cell carcinoma with subcutaneous interleukin 2: evidence for non-renal clearance of cytokines

“…The treatment response and toxicity data for these patients has already been reported in detail as part of a larger study (Joffe et al, 1996). The anephric patient experienced no more appreciable toxicity than the other patients studied, with grade 2 toxicity in terms of fatigue, pyrexia, dry skin, flushes, anorexia, vomiting and headache.…”

“…regimens employed, most notably a capillary leak syndrome (similar to that seen in patients with septic shock) manifest by hypotension, weight gain, acute renal failure and pulmonary oedema (Whittington and Faulds, 1993). Newer approaches using lower dose subcutaneous (s.c.) IL-2 have been promising with, for example, recent combination regimens producing objective responses with less accompanying toxicity in 30-40% of patients with metastatic renal cell carcinoma (Atzpodien et al, 1990;Atzpodien-et al, 1993;Joffe et al, 1996).An understanding of cytokine metabolism is important for ensuring a rational approach to the design of therapeutic strategies, particularly with regard to route of administration and dosage. The mechanism of clearance is an important consideration as IL-2, for example, may be administered to patients who have undergone a nephrectomy, occasionally bilateral nephrectomies, and IL-2 itself may cause renal dysfunction.…”

“…regimens employed, most notably a capillary leak syndrome (similar to that seen in patients with septic shock) manifest by hypotension, weight gain, acute renal failure and pulmonary oedema (Whittington and Faulds, 1993). Newer approaches using lower dose subcutaneous (s.c.) IL-2 have been promising with, for example, recent combination regimens producing objective responses with less accompanying toxicity in 30-40% of patients with metastatic renal cell carcinoma (Atzpodien et al, 1990; Atzpodien-et al, 1993;Joffe et al, 1996).…”

“…In support of an alternative clearance mechanism at lower doses are the brief reports of the treatment of three anephric patients with s.c. IL-2, two of whom experienced similar toxicity to that experienced by many patients with normal renal function apart from more pronounced hypotension (Buter et al, 1992) and the other experiencing more severe toxicity (OMS . grade 3), necessitating a dose reduction from 18 to 9 x 106 Units of IL-2 (Suc et al, 1995 (Joffe et al, 1996). Seven patients had histologically proven metastatic renal cell carcinoma and one had a Bellini duct tumour.…”

Are cytokine responses in renal cell cancer the product of placebo effect of treatment or true biotherapy? What trials are needed now?

“…Easy access to ultrasound, leading to early diagnosis of renal tumours, and more frequent treatment of patients at a stage when they only have small-volume lung metastases with a high chance of response (Lopez Hanninen et al, 1996) are factors possibly explaining why the German data have for so long been felt to be so different from what can be achieved in other countries. This has been particularly so in the UK where most GPs have to wait 1-3 months for such a procedure to be performed and the response rate to the Atzpodian regimen has been half that seen in Germany (Joffe et al, 1996). The new MRC/EORTC trial is an adjuvant study that focuses on high-risk patients with vascular, lymphatic or local invasion (T3/T4) in complete remission after surgery.…”