2.0 BACKGROUND AND RATIONALE 
2.1 CURRENT STATUS OF THERAPY FOR METASTATIC RENAL CELL CARCINOMA 
MEDICAL THERAPY 
New treatment is needed for metastatic renal cell carcinoma (RCC). 1,2 
The 5-year survival rate of Stage IV disease is 2%; median survival is about 
18 months. 1,2,3,4 For patients with supra-diaphragmat ic extension of RCC into the 
vena cava (Stage III, T4b disease), and without radiographic evidence of 
distant metastases at surgery, the 5-year survival is equally dismal. To date 
chemotherapy and radiotherapy strategies have not shown any survival 
benefit . ' ,2,3,4 
Spontaneous, short-term regressions of RCC metastases have been reported 
in up to l%-7% of RCC patients. 2,5 This clinical observation suggests a role 
for host anti-tumor immunity in this disease, and fosters continued interest 
in immunotherapy. Interferon-alpha has been investigated as a treatment for 
metastatic RCC, with major responses observed in 10% to 21% of patients 
without clearly improved survival. 5 ’ 9 Interleukin-2 (IL-2) has been approved 
by the FDA for the treatment of metastatic RCC after initial trials reported 
significant partial and complete response rates in up to one third of patients 
when used with LAK cells. 10,11,12,13 Subsequent trials reported objective tumor 
response rates ranging from 0% to 35% of RCC patients with various schedules — 
with or without the infusion of LAK cells. 10 ' 27 Complete responses, when they 
occur, may be durable for over 18 months. Associated with a complete response 
rate of 4% is a 4%-6% mortality rate from IL-2 treatment, according to the FDA 
approved package insert. 28 Most recently, a multi-institution phase II trial 
of rhuIL-2 and interferon alpha in metastatic RCC reported in July 1992 a 
complete response in 1 of 34 (3%) patients, toxicity in 4 of 34 (12%) patients 
requiring ICU admissions, and IL-2-related deaths in 2 of 34 (6%). 24 
Investigational therapy thus remains a "standard of care" option for properly 
informed RCC patients. Phase I immunotherapy trials fall in this category, as 
well as phase I studies of novel cytotoxic drugs. Patients disinclined to be 
treated with IL-2, or participate in investigational trials are managed 
symptomatically. 
SURGICAL THERAPY 
Radical nephrectomy is the only curative treatment for RCC in Stage 
I, II, and III disease. 1,2 Nephrectomy in advanced stage RCC patients (Stage 
III T4b and Stage IV) is used to palliate or forestall morbidity from 
complications of local tumor invasion into the great vessels or adjacent 
organs. 1,2 Nephrectomy has not been shown in itself to prolong survival in 
Stage IV disease. 1,2 In appropriate surgical candidates with Stage IV disease, 
however, nephrectomy has also been employed widely for preparation of 
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