Immunochemotherapy with interleukin-2, interferon- α and 5-fluorouracil for progressive metastatic renal cell carcinoma: a multicenter phase II study

Abstract

In patients with metastatic renal cell carcinoma response rates of 7–26% have been achieved with immunotherapy. A high response rate of 48% in 35 patients has been reported for treatment with the combination of interferon-α (IFN-α), interleukin-2 (IL-2) and 5-fluorouracil (5-FU) (Atzpodien et al (1993 a ) Eur J Cancer 29A : S6–8). We conducted a multicentre phase II study to confirm these results. Metastatic renal cell carcinoma patients were treated as outpatients with an 8-week treatment cycle. Recombinant human IL-2 20 MU m −2 was administered subcutaneously (s.c.) three times a week (t.i.w) in weeks 1 and 4 and 5 MU m −2 t.i.w. in weeks 2 and 3. Recombinant human IFN-α 2a 6 MU m −2 was administered s.c. once in weeks 1 and 4 and t.i.w. in weeks 2 and 3, and 9 MU m −2 t.i.w. in weeks 5–8. 5-FU (750 mg m −2 ) was given as a bolus injection intravenous once a week in weeks 5–8. The treatment cycle was repeated once in case of response or minor response. Fifty-two patients entered the study. All had undergone a nephrectomy and had progressive metastatic disease. The median WHO-performance status was 1, the median number of metastatic sites was 2 (range 1–5) and the median time between the diagnosis of the primary tumour and the start of treatment was 12.9 months (range 1–153). Among the 51 patients, including four patients with early progressive disease, who were evaluable for response, the response rate was 11.8% (95% confidence interval (CI) 2.9–20.7%), with no complete responses. Median duration of response was 8.3 (range 3.8–22.4+) months. Median survival was 16.5 (range 1.8–30.5+) months. Grade 3/4 toxicity (WHO) occurred in 29/52 (55.8%) of the patients in cycle 1 and in 6/16 (37.5%) of the patients in cycle 2. It consisted mainly of anorexia, fatigue, nausea, fever and leucocytopenia. We cannot confirm the high response rate in patients with metastatic renal cell carcinoma treated with the combination of IFN-α, IL-2 and 5-FU, as described by Atzpodien et al. © 2000 Cancer Research Campaign

Subcutaneous interleukin-2, interferon alpha-2b and 5-fluorouracil in metastatic renal cell carcinoma as second-line treatment after failure of previous immunotherapy: a phase II trial

“…This protocol is closely related to the schedule designed for other clinical research trials with IL-2, IFNa and 75-FU within the framework of the French Immunotherapy Group Négrier et al, 2000). These large studies showed an unexpectedly low response rate Négrier et al, 2000) like the present study, compared to more promising results obtained by others (Atzpodien et al, 1993;Hofmockel et al, 1996;Joffe et al, 1996;Ellerhorst et al, 1997;Tourani et al, 1998;Allen et al, 2000;Dutcher et al, 2000;Elias et al, 2000;van Herpen et al, 2000).…”

Metastatectomy prior to Immunochemotherapy for Metastatic Renal Cell Carcinoma

“…Since many of our subject samples had undergone metastatectomy prior to immunochemotherapy, it is possible that those who would have shown responses to subsequent systemic therapy may have been masked by prior surgery. On the other hand, there have been others who have similarly reported lower response rates for the triple therapy compared with our results [1,27] . Although it is one of the most widely used systemic treatment for metastatic renal cell carcinoma, controversy still exists regarding the actual effi cacy of triple combination immunochemotherapy, and it is still considered as more of a palliative approach of treatment.…”

CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

“…Response rates remain low at around 15%, and the toxicity of high-dose IL-2 limits its use (Krown, 1987;Muss, 1998;Kammula, 1998;van Herpen et al, 2000). Targeted therapeutics are relatively new to the oncology field, most acting via the inhibition of mitotic signalling kinases.…”