A phase II trial of pemetrexed plus gemcitabine in locally advanced and/or metastatic transitional cell carcinoma of the urothelium.

BACKGROUND: Both pemetrexed and gemcitabine have single-agent activity in bladder cancer, but the combination of these two drugs has not been previously evaluated for safety and efficacy in this disease. Thus, the objectives in the current study were to determine overall response rate (ORR), progression-free survival, overall survival and safety and toxicity in chemonaive patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium. PATIENTS AND METHODS: Gemcitabine 1250 mg/m2 was administered over 30 min i.v. on days 1 and 8, and pemetrexed 500 mg/m2 over 10 min i.v. on day 8 after gemcitabine, every 21 days. RESULTS: Sixty-four patients were enrolled, 11 female and 53 male, median age 65 years (range 38-81), median WHO performance status of 1. Visceral metastases were present in 55% of patients. ORR among 47 patients evaluable for response was 28% (95% CI 16% to 43%) and ORR for the intention-to-treat population was 20% (95% CI 11% to 32%) with three CR and 10 PR. Median response duration was 11.2 months and median overall survival 10.3 months (95% CI 8.1-14.6 months). CTC grade 3/4 hematologic toxicities included anemia (19%), thrombocytopenia (9%), neutropenia (38%), febrile neutropenia (17%) and neutropenic sepsis (3%). Grade 3/4 non-hematologic toxicities included elevated transaminases (12%), dyspnea (8%), fatigue (8%) and stomatitis (5%). There was one toxic death due to neutropenic sepsis. CONCLUSIONS: The combination of pemetrexed and gemcitabine had a manageable safety profile. However, efficacy was apparently not superior to that of single-agent gemcitabine.

Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model.

We aimed to create a prognostic model in metastatic melanoma based on independent prognostic factors in 321 patients receiving interleukin-2 (IL-2)-based immunotherapy with a median follow-up time for patients currently alive of 52 months (range 15-189 months). The patients were treated as part of several phase II protocols and the majority received treatment with intermediate dose subcutaneous IL-2 and interferon-alpha. Neutrophil and monocyte counts, lactate dehydrogenase (LDH), number of metastatic sites, location of metastases and performance status were all statistically significant prognostic factors in univariate analyses. Subsequently, a multivariate Cox's regression analysis identified elevated LDH (P<0.001, hazard ratio 2.8), elevated neutrophil counts (P=0.02, hazard ratio 1.4) and a performance status of 2 (P=0.008, hazard ratio 1.6) as independent prognostic factors for poor survival. An elevated monocyte count could replace an elevated neutrophil count. Patients were assigned to one of three risk groups according to the cumulative risk defined as the sum of simplified risk scores of the three independent prognostic factors. Low-, intermediate- and high-risk patients achieved a median survival of 12.6 months (95% confidence interval (CI), 11.4-13.8), 6.0 months (95% CI, 4.8-7.2) and 3.4 months (95% CI, 1.2-5.6), respectively. The low-risk group encompassed the majority of long-term survivors, whereas the patients in the high-risk group with a very poor prognosis should probably not be offered IL-2-based immunotherapy.

Safety and efficacy of subcutaneous and continuous intravenous infusion rIL-2 in patients with metastatic renal cell carcinoma.

A retrospective analysis was conducted on data from four open-label, nonrandomised, phase II trials of recombinant interleukin-2 (rIL-2) in patients with metastatic renal cell carcinoma to compare the safety and efficacy of administration by subcutaneous (s.c.) and continuous intravenous (c.i.v.) infusion (n=103 s.c. and n=225 c.i.v.). No statistically significant differences were found between the cohorts in terms of overall response rate (s.c.: 13.6% vs c.i.v.: 12.4%, P=0.77), response duration (s.c.: 9.8 months vs c.i.v.: 10.1 months, P=0.99), and overall survival (P=0.08). Compared with c.i.v. administration, more patients in the s.c. cohort experienced stable disease (50.5 vs 29.8%) and fewer underwent disease progression (35.0 vs 43.6%). Subcutaneous administration was associated with a significantly lower incidence of grade 3 or 4 adverse events (46 vs 76%; P<0.001), and fewer s.c. patients required dose reductions because of toxicity (20 vs 82%). At the doses and within the schedules tested, this comparative analysis did not detect any difference in efficacy between s.c. and c.i.v. administration of rIL-2 in terms of overall survival, duration of response and response rate in patients with metastatic renal cell carcinoma. However, s.c. delivery of rIL-2 was associated with improved tolerability.

[Cervical lymphatic metastases from occult primary tumor. A nation-wide 20-year study from the Danish society of head and neck oncology]. / Lymfeknudemetastaser på halsen fra ukendt primaertumor. En landsdaekkende 20-års opgørelse fra Dansk Selskab for Hoved- og Halsonkologi.

INTRODUCTION: The management of patients with cervical lymph node metastases from unknown primary tumours is a major challenge in oncology. This study presents data collected from all five oncology centres in Denmark. MATERIALS AND METHODS: Of the 352 consecutive patients with squamous cell or undifferentiated tumours seen from 1975 to 1995, a total of 277 (79%) were treated with radical intent. Most patients received radiotherapy to both sides of the neck as well as elective irradiation of the mucosal sites in nasopharynx, oropharynx, hypopharynx and larynx (81%). Irradiation of the ipsilateral neck only was done in 26 patients (10%). Radical surgery was the only treatment in 23 N1-N2 patients (9%). RESULTS: The five-year estimates of neck control, disease-specific survival and overall survival for radically treated patients were 51%, 48% and 36%, respectively. The emergence of the occult primary was observed in 66 patients (19%). About half of the emerging primaries were within the head and neck region with oropharynx, hypopharynx and oral cavity being the most common sites. Emerging primaries outside the head and neck region were primarily located in the lung (19 patients) and oesophagus (five patients). The most important factor for neck control was nodal stage (5-year estimates 69% [N1], 58% [N2] and 30% [N3]). Other important parameters for neck control and disease-specific survival included haemoglobin, gender and overall treatment time. Patients treated with ipsilateral radiotherapy had a relative risk of recurrence in the head and neck region of 1.9 compared to patients treated at both neck and mucosa. At five years, the estimated control rates were 27% (ipsilateral) and 51% (bilateral; p = 0.05). The 5-year disease-specific survival estimates were 28% and 45%, respectively (p = 0.10). DISCUSSION: Extensive irradiation to both sides of the neck and the mucosa in the entire pharyngeal axis and larynx resulted in significantly fewer loco-regional failures compared to patients treated with ipsilateral techniques, but only a trend towards better survival. Determination of the optimal strategy in terms of loco-regional control, survival and morbidity requires a prospective randomized trial.

Predictive factors of response to cisplatin-based chemotherapy and the relation of response to survival in patients with metastatic urothelial cancer.

PURPOSE: To identify pretreatment variables predicting overall and complete response to cisplatin-based chemotherapy for metastatic urothelial cancer, and to study the relation between response and the duration of survival. PATIENTS AND METHODS: A total of 119 evaluable patients with recurrent locally advanced or metastatic urothelial cancer received cisplatin-based combination chemotherapy in four consecutive phase II studies from 1987 to 1997. The relationship of pretreatment variables and response was evaluated with logistic regression, and prognostic factors for survival were analyzed with Cox's multivariate model. RESULTS: Response was achieved in 49% of the patients with a complete response rate of 15%. Good performance status and absence of bone metastases were independently predictive of overall response. Good performance status and normal hemoglobin were independently predictive of complete response. Median survival was 8.9 months. Performance status, alkaline phosphatase, s-creatinine, liver and bone metastases were independent prognostic factors for survival. Median survival was 12.4 months in responding patients and 6.3 in nonresponding patients. Response to chemotherapy was included in the multivariate model and was the strongest prognostic factor for survival. CONCLUSION: The presence of bone metastases, low hemoglobin or poor performance status predicts decreased chance of response to chemotherapy. Response to chemotherapy is an independent prognostic factor for prolonged survival in patients with metastatic urothelial cancer.

Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology.

BACKGROUND AND PURPOSE: The management of patients with cervical lymph node metastases from unknown primary tumours is a major challenge in oncology. This study presents data collected from all five oncology centres in Denmark. MATERIAL AND METHODS: Of the 352 consecutive patients with squamous cell or undifferentiated tumours seen from 1975 to 1995, a total of 277 (79%) were treated with radical intent. The general treatment policy at all centres during the entire study period has been to treat all suitable candidates with radiotherapy to both sides of the neck and include elective irradiation of the mucosal sites in nasopharynx, and larynx, hypopharynx and larynx (81%). Irradiation of the ipsilateral neck only was done in 26 patients (10%). Radical surgery was the only treatment in 23 N1-N2 patients (9%). RESULTS: The 5-year estimates of neck control, disease-specific survival and overall survival for radically treated patients were 51, 48 and 36%, respectively. The emergence of the occult primary was observed in 66 patients (19%). About half of the emerging primaries were within the head and neck region with oropharynx, hypopharynx and oral cavity being the most common sites. Emerging primaries outside the head and neck region were primarily located in the lung (19 patients) and oesophagus (five patients). The frequency of emerging primary in the head and neck was significantly higher in patients treated with surgery alone, the actuarial risks at 5-year being 54+/-1% (no RT) vs. 15+/-3% (with RT), P<0.0001. The most important factor for neck control was nodal stage (5-year estimates 69% (N1), 58% (N2) and 30% (N3)). Other important parameters for neck control and disease-specific survival included haemoglobin, gender and overall treatment time. Patients treated with ipsilateral radiotherapy had a relative risk of recurrence in the head and neck region of 1.9 compared with patients treated to both neck and mucosa. At 5 years, the estimated control rates were 27% (ipsilateral) and 51% (bilateral; P=0.05). The 5-year disease-specific survival estimates were 28 and 45%, respectively (P=0.10). CONCLUSIONS: This study has confirmed that patients with neck node metastases from occult head and neck cancer have clinical features and prognosis similar to other head and neck malignancies. Extensive irradiation to both sides of the neck and the mucosa in the entire pharyngeal axis and larynx resulted in significantly less loco-regional failures compared with patients treated with ipsilateral techniques, but only a trend towards better survival. A prospective randomized trial is required to determine the optimal strategy in terms of locoregional control, survival and morbidity.

Subcutaneous interleukin-2 and interferon-alpha plus cisplatin with and without prophylactic cimetidine in patients with metastatic malignant melanoma: a phase II study.

A phase II study was performed to evaluate the efficacy of cisplatin combined with interleukin-2 and interferon-alpha2b administered subcutaneously to patients with metastatic malignant melanoma (MMM). Between April 1994 and January 1999, 87 patients with MMM and a WHO performance status of < or = 2 were entered into the study. The first 42 patients had prophylactic cimetidine; the other 45 patients did not. An overall response rate of 27% was achieved in the 82 patients evaluable for response. The median response duration was 7.0 months (range 4.4-29.0 months). The median survival for all patients was 10.1 months (range 0.4-64.9+ months). Toxicity was substantial but generally manageable and usually reversed on dose reduction or temporary interruption of treatment. Two patients (2%) died of treatment-related toxicity. No difference in response or survival was seen in the patients treated with or without cimetidine. In multivariate analysis, lactate dehydrogenase level (P < 0.001), number of metastatic sites (P = 0.014) and performance status (P = 0.035) was shown to be independent prognostic factors for survival. This high dose interleukin-2 subcutaneous regimen resulted in a small fraction of long-term survivors. The response and survival results were not superior to other studies using lower and less toxic interleukin-2 doses.

Efficient palliation of haemorrhaging malignant melanoma skin metastases by electrochemotherapy.

Electric pulses can cause transient permeabilization of cell membranes (electroporation) and this can be utilized to increase the uptake of chemotherapy (electrochemotherapy). Preclinical studies have shown that in vivo electroporation causes transient shut down of blood flow both in normal and, in particular, malignant tissues. We report the successful palliation of a malignant melanoma patient with bleeding skin metastases using electrochemotherapy. In an on-going study of combined electrochemotherapy and low dose interleukin-2, one patient with bleeding skin metastases was included. Nine skin metastases, of which seven were ulcerated, were treated. After intratumoral bleomycin injection, needle electrodes with two arrays 4 mm apart were inserted into the tumours. Eight square wave electric pulses each 99 micros in duration and with an applied voltage to electrode distance ratio of 1.2 kV/cm were administered. In all the treated lesions, bleeding immediately stopped on administration of the electric pulses and did not recur. The treated metastases developed crusts and the lesions healed in a matter of weeks. Treatments were given under local anaesthesia, lasted a few minutes, and patient discomfort was brief and modest. In conclusion, we propose that electrochemotherapy should be considered for the palliation of haemorrhaging metastases as it is an efficient, tolerable, brief, outpatient, once-only treatment.

Effect of chemotherapy on carcinoma in situ of the testis.

BACKGROUND: Approximately 5% of patients with testicular cancer harbour carcinoma in situ (CIS) in the contralateral testis. CIS will progress into invasive tumour in about 50% of cases within five years. The present study evaluated the effect of platinum containing chemotherapy on CIS. PATIENTS AND METHODS: Thirty-three patients with disseminated germ-cell cancer and biopsy proven CIS of the testis were evaluated. RESULTS: CIS had disappeared in the first follow-up biopsy in 30 patients. Six patients had a relapse of CIS with or without invasive cancer after 30, 31, 47, 51, 76 and 95 months from start of chemotherapy. Two relapses were among six patients who initially received cisplatin, vinblastine and bleomycine and four among 27 patients who initially received cisplatin, etoposide and bleomycine. The estimated cumulative risk of CIS five and 10 years after chemotherapy was 21% and 42%, respectively. The estimated cumulative incidence of spermatogenesis was 64% and 81% at five and 10 years of follow-up, respectively. CONCLUSION: Platinum containing chemotherapy may eradicate CIS. However, patients with CIS may develop invasive cancer in spite of chemotherapy. In the light of the present data, we recommend radiotherapy to the affected testicle in patients with CIS in the contralateral testis and in patients with bilateral testicular CIS. In patients with extragonadal disease and CIS in one testicle, orchiectomy of the affected testicle is recommended. In patients for whom future fertility is an important issue, follow-up including repeated biopsies can be offered for a period of at least 10 years.

Renal haemodynamics, sodium and water reabsorption during continuous intravenous infusion of recombinant interleukin-2.

1. Renal haemodynamics, lithium and sodium clearance were measured in 14 patients treated with recombinant interleukin-2 for metastatic renal cell carcinoma. 2. Patients were studied before and after 72 h of continuous intravenous infusion of recombinant interleukin-2 (18x10(6) i.u..24 h-1.m-2) and 48 h post therapy. Cardiac output was measured by impedance cardiography. Effective renal plasma flow and glomerular filtration rate were determined by the renal clearances of 131I-hippuran and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) respectively. Renal clearance of lithium (CLi) was used as an index of proximal tubular outflow. 3. Treatment caused a transient decrease in mean arterial blood pressure and systemic vascular resistance, but cardiac output remained unchanged. Renal blood flow decreased and renal vascular resistance increased during and after treatment. Sodium clearance decreased from 1.10 (0.63/1.19) ml/min to 0.17 (0.18/0.32) ml/min (P=0.003). Glomerular filtration rate remained unchanged, whereas the median CLi decreased from 26 (17/32) ml/min to 17 (10/21) ml/min (P=0.008). Calculated absolute proximal reabsorption rate of water increased from 63 (40/69) ml/min to 71 (47/82) ml/min (P=0.04). The urinary excretion rate of thromboxane B2 and the ratio between excretion rates of thromboxane B2 and 6-keto-prostaglandin-F1alpha increased by 98% (P=0.022) and 175% (P=0.022) respectively. 4. The study suggests a specific recombinant interleukin-2-induced renal vasoconstrictor effect. Changes in renal prostaglandin synthesis may contribute to the decrease in renal blood flow. The lithium clearance data suggest that an increased proximal tubular reabsorption rate may contribute to the decreased sodium clearance during recombinant interleukin-2 treatment.

Infections in patients treated with high-dose chemotherapy for germ cell tumours.

25 patients with disseminated germ cell tumours were treated with high-dose cisplatin and etoposide (40 mg/m2 and 200 mg/m2 daily x five, respectively) leading to severe myelosuppression. A comprehensive study was undertaken in order to identify and describe the bacterial, viral and fungal infections in this group of patients. Fever (> 38.5 degrees C) and leucopenia (white blood cell count < 1.0 x 10(9)/l) were observed in 61 of 90 treatment cycles (68%). A microbiological aetiology compatible with the clinical manifestations of infection could be identified in 33 of the 61 febrile episodes (54%). Bacteraemia occurred in 14 episodes in 12 patients. Eight episodes (57%) involved gram-positive aerobic bacteria.

A phase II study of cisplatin plus methotrexate with folinic acid rescue in metastatic or locally recurrent transitional cell carcinoma of the urothelium.

34 patients with metastatic or recurrent transitional cell carcinoma (TCC) of the urothelium were treated with cisplatin 100 mg/m2 plus methotrexate 250 mg/m2 with folinic acid rescue every 3 weeks. A response rate of 55% was achieved with two complete and 15 partial responses in 31 evaluable patients. The overall median survival was 7 months, 9 months for responding and 4 months for non-responding patients. Toxicity was generally moderate. However, 1 patient with previous infectious problems died of neutropenic sepsis. Overall, 83% of the scheduled doses of cisplatin and 96% of the scheduled doses of methotrexate were given. In conclusion, this schedule of the combination of cisplatin and methotrexate did not improve response rate or survival compared with previous studies of this two-drug combination.

A comparison of 2 modes of administration of recombinant interleukin-2: continuous intravenous infusion alone versus subcutaneous administration plus interferon alpha in patients with advanced renal cell carcinoma.

PURPOSE: To compare 2 treatment modalities with recombinant Interleukin-2 (rIL-2) for patients with advanced Renal Cell carcinoma (RCC): continuous intravenous infusion (CIV) alone versus subcutaneous (s/c) rIL-2 + Interferon-alpha (IFN-alpha). PATIENTS AND METHODS: Data have been collected on 425 patients with RCC, treated CIV rIL-2 alone, (225 patients), or rIL-2 by the s/c route (200 patients). Patients receiving s/c rIL-2 also received s/c IFN-alpha both drugs being administered on an outpatient basis. Patients receiving CIV rIL-2 were treated as inpatients. Patient eligibility criteria were similar on all studies, and included patients with progressive, advanced disease, but with an ambulatory performance status. RESULTS: The overall response rate for the CIV schedules was not significantly different from the s/c regimens: 15% (95% confidence limits (CL) 10-20%) vs 20% (95%CL 14-26%) with 4% CR in both approaches. Durable responses were seen in both CIV and s/c schedules and there was no evidence of a significant difference in survival in multivariate analysis. There was however an important shift in the toxicity profile. The s/c regimens do not induce a clinically detectable capillary leak syndrome, which is the dose limiting toxicity for CIV regimens. CONCLUSION: Although the introduction of CIV regimens of rIL-2 was a major step forward compared to high-dose bolus, because most patients could be treated in a normal oncology ward, the s/c schedule of rIL-2 + IFN-alpha offers the possibility of outpatient (home) therapy, with no evidence of a reduction in efficacy.

[Malignant melanoma of the skin in Denmark--epidemiology, diagnosis and treatment]. / Melanoma malignum cutis i Danmark--epidemiologi, diagnostik og behandling.

About 700 new cases of malignant melanoma of the skin are registered annually in Denmark. The incidence is increasing rapidly and the number of new cases increases by more than 5% per annum. The most important phenotypical risk factors are the number of acquired pigmented naevi and exposure to sunlight is the most important risk factor in the external environment so that severe sunburn in children and intermittent intense exposure to sunlight increase the risk of melanoma. The thickness of the tumour at the time of the diagnosis is the most important prognostic factor. The prognosis deteriorates with increasing thickness. Treatment is primarily surgical. In cases of inoperable local melanoma and regional recurrences, irradiation may be administered. Chemotherapy and/or immunotherapy are of experimental character. In the light of the rapidly increasing incidence, it is important that knowledge of risk factors for development of the disease and the clinical characteristics of early melanoma is spread to not only the medical profession but also to the general public.

Treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2: a single-center phase II study.

PURPOSE: A single-center phase II study was performed to evaluate the efficacy of recombinant interleukin-2 (rIL-2) administered by continuous infusion to patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty-one patients with RCC were entered onto the study. rIL-2 (Proleukin; Eurocetus Corp, Amsterdam, The Netherlands) was administered intravenously in a dose of 18 x 10(6) IU/m2 per 24 hours. A maximum of two induction cycles and four maintenance cycles were given. Each induction cycle consisted of two rIL-2 infusion periods of 120 hours and 108 hours duration, respectively; these were separated by a 6-day rest period. Each maintenance cycle consisted of a 120 hours rIL-2 infusion period. RESULTS: Six of 30 assessable patients (20%) responded; two (7%) with a complete response (CR) and four (13%) with a partial response (PR). The response duration for patients with CR was 209 and 715+ days, and for those with PR 161, 197, 245, and 353 days. Seven patients had stable disease (SD) with a median duration of 261 days (range, 127 to 381 days). The overall median survival was 261 days (range, 13 to 905+ days). The most frequent toxicities requiring dose reductions of rIL-2 were: hypotension in 87% of patients, dyspnea in 32%, CNS toxicity in 55%, and an increase in serum creatinine levels in 48%. Septicemia occurred in 16% of patients. Toxicities usually reversed on interruption of rIL-2 infusion. One patient (3%) died as a result of the treatment from initial CNS toxicity followed by multiorgan failure. CONCLUSIONS: The study confirmed the antitumor efficacy of rIL-2 administered by continuous infusion in patients with metastatic RCC. The response rate was similar to that obtained by high-dose bolus injections of rIL-2. Toxicity was substantial but manageable in a specialized oncology ward without routine use of an intensive care unit.

In vitro production of TNF-alpha, IL-1 beta and IL-6 by mononuclear blood cells of patients with renal cell carcinoma undergoing rIL-2 treatment. Relation between clinical response and TNF-alpha production.

The purpose of this study was to examine the production of IL-1 beta, IL-6 and TNF-alpha by peripheral blood mononuclear cells in patients with renal cell carcinoma treated with recombinant interleukin 2 (rIL-2). Peripheral blood mononuclear cells (PBMC) were purified from blood samples obtained six times during therapy and the production of IL-1 beta, IL-6 and TNF-alpha were determined after 18 h culture of the PBMC in culture medium or in medium containing 10 micrograms lipopolysaccharide (LPS)/ml, 10 ng LPS/ml or 1000 units rIL-2/ml. In vivo therapy with rIL-2 resulted in substantial changes in the production of the three cytokines. Only the production of TNF-alpha following in vitro stimulation with rIL-2 was related to the clinical response, being significant lower in responding patients than in non-responders (P less than 0.05). These findings suggest that the rIL-2-induced TNF-alpha production of PBMC in vitro is lower in renal cancer patients that respond to rIL-2 therapy than in non-responding patients.

Recombinant interleukin-2 and lymphokine-activated killer cell treatment of advanced bladder cancer: clinical results and immunological effects.

The purpose of this study was to evaluate the efficacy of treatment with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells in patients with advanced bladder cancer and to study the induced changes in the distribution of leukocyte subsets in blood and tumor. Nine patients with metastatic transitional cell cancer of the bladder were treated with a continuous infusion of rIL-2 combined with lymphocytes stimulated in vitro with rIL-2. None of the patients responded to the therapy despite substantial changes observed in the immunological cells, both in tumor and blood. The rIL-2 infusion induced migration of leukocytes to the tumors, which was related to increased expression of the adhesion molecule VLA-1 on both peripheral blood mononuclear cells and the endothelial cells of small tumor vessels. Only T-cells, predominately expressing IL-2 receptors, and macrophages infiltrated the tumors. Natural killer cells remained few or absent in the tumors, even though the natural killer cells in peripheral blood were activated by the treatment. This study shows that the present technique of rIL-2 and lymphokine-activated killer cell therapy is able to induce substantial changes in the immune system of patients with metastatic bladder cancer. However, this treatment did not induce tumor regression, which may be due to the advanced stage of disease.

Recombinant interleukin-2 in metastatic renal cell carcinoma--a European multicentre phase II study.

This multinational, multicentre study represents the introduction of recombinant interleukin-2 (rIL-2) in Europe. From December 1987 to June 1989, 57 eligible patients with metastatic renal cell cancer were treated with rIL-2 administered as continuous intravenous infusion. 8 out of 51 evaluable patients responded (16%), 2 complete remission (CR) and 6 partial remission (PR). 10 patients had no change (20%). The response duration for CR was 209 and 394+ days. The median response duration for PR was 371 (range 140-506+) days. Dose-limiting grade 3-4 toxicities were hypotension in 52% of the patients, arrhythmia (4%), dyspnoea (8%), creatinine rise (4%), peripheral neurotoxicity (10%) and central neurotoxicity (10%). Toxicities most often recovered solely on interrupted therapy. 2 patients died due to catheter-related septicaemia and one patient died of rIL-2 induced renal failure. The study confirmed the antitumour efficacy of rIL-2 in renal cell cancer. Toxicities were numerous, but manageable by close observation in a normal oncology ward without routine use of an intensive care unit.