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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-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU) (Atzpodien et al (1993a) Eur J Cancer29A: 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-alpha 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-alpha, IL-2 and 5-FU, as described by Atzpodien et al.

High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis.