Annals of Oncology 13:606-613, 2002
© 2002 European Society for Medical Oncology
A multi-institutional phase II trial of a novel inpatient schedule of continuous interleukin-2 with interferon 
-2b in advanced renal cell carcinoma: major durable responses in a less highly selected patient population
1Edward Hines Jr VA Hospital, Hines, IL; 2Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL; 3Northwestern University Medical School, Chicago, IL; 4Lutheran General Hospital, Park Ridge, IL; 5University of Illinois at Chicago, IL, USA
Received 27 June 2001; revised 19 September 2001; accepted 23 October 2001.
Background
A prospective multi-institutional phase II trial was undertaken to define the activity and toxicity of a unique decrescendo infusion of interleukin-2 (IL-2) in combination with interferon (IFN) in patients with metastatic renal cell carcinoma. The identical regimen has shown promise in advanced melanoma.
Patients and methods
Between February 1997 and March 1999, 47 patients with metastatic renal cell carcinoma, from five institutions, were treated with outpatient s.c. IFN (10 mU/m2/day) on days 1–5, followed by inpatient IL-2 via continuous i.v. decrescendo infusion [18 million International Units (MIU) (1 mg)/m2/6 h, followed by 18 MIU/m2/12 h, then 18 MIU/m2/24 h and 4.5 MIU/m2/24 h for the following 3 days] on days 8–12, in a hospital ward without intensive care unit (ICU)-type monitoring. Treatment was repeated every 4 weeks. In contrast to high dose IL-2 protocols, patient eligibility did not require pulmonary function tests and allowed serum creatinine up to 2 mg/dl.
Results
Among 44 eligible patients, 57% (25) had their primary in place, 57% (25) had bone or visceral involvement, and only 4% (2) had lung as their only site of disease. The overall response rate in 43 response-evaluable patients was 16.3% [95% confidence interval (CI) 5.3 to 27.3], with three complete responses and four partial responses observed. The median survival was 13 months; nine patients remain alive at >23 months. The median duration of response is 36 months (range 11.5 to 48+ months). Toxicity was modest, consisting of typical cytokine-induced systemic symptoms and rare organ dysfunction. Severe grade 4 toxicity occurred in only 13% of the 130 cycles.
Conclusions
This unique, reasonably well tolerated IL-2/IFN combination induced a modest response rate with a number of durable remissions. While the optimal IL-2-based regimen for the treatment of advanced renal cell carcinoma remains elusive, the present regimen should attract considerable interest. This is based on tumor activity very similar to high dose IL-2 in a patient population not as carefully selected for optimal organ function.
Key words: decrescendo IL-2, interferon, kidney cancer, phase II