Long-term survival after continuous infusion interleukin-2

Between 1987-1990, 612 patients received high-dose continuous intravenous interleukin-2 (IL-2) in phase II clinical trials of the National Biotherapy Study Group (NBSG). The purpose of this analysis was to determine the long-term survival rates associated with such therapy and the correlation, if any, between objective tumor response, and survival.

Patients who are known to have survived at least 3 years or more were identified. Actual and actuarial survival rates were determined for various malignancies and by tumor response.

At least 37 (6.0%) survived > or = 3 years from the initiation of IL-2 therapy, and it is possible the 3-year survival rate is as high as 20%. This included 14/168 (8%) of patients with renal cell carcinoma, 10/175 (6%) melanoma, 2/51 (4%) lung cancer, 0/61 colorectal, 0/36 breast, 1/17 sarcoma, 1/14 pancreas, 1/19 ovary, 3/11 lymphoma, 2 adenocystic carcinomas, 2 carcinoid, and one Hodgkin's disease. Four hundred ninety-one of 612 (80%) are known to have died, 121 were still alive at the time of the last follow-up. Median survival was 7.9 months. Among 547 evaluable patients, there were eight complete responses (CR) and 42 partial responses (PR), for an objective response rate of 9%. An additional 32 patients had mixed or minimal responses (MR) for a total response rate of 15%. The 3-year survival rates were 25% for PR, 17% for PR, 16% for MR, 8% for stable disease (SD), and 2% for patients with progressive disease (PD). Responders made up a higher proportion of patients who survived > or = 3 years than of patients who survived < or = 3 years (14/37 = 38% vs 68/500 = 14%; p < .0001, X2). A higher proportion of responders survived > or = 3 years than non-responders (14/82 = 17% vs 23/230 = 4%, p < .0001, X2). Patients with CR, PR, or MR had a > or = 3-year survival rate (14/82 = 17%) than patients who had SD (20/249 = 8%; p = .02, x2, who in turn had a > or = 3-year survival rate that was greater than patients who had PD (3/206 = 2%; p = .001, X2). For individual trials in which 10 or more patients were enrolled, the percentage of patients surviving > or = 3 years ranged between 4% and 8%.

We conclude that in the setting of IL-2 therapy for metastatic cancer, the probability of surviving > or = 3 years was approximately 12 times greater for responders, and five times greater for patients with SD; as compared to patients who had PD. Furthermore, despite diagnoses of metastatic cancer, often in settings in which disease had been refractory to standard therapy there was an actual 3-year survival rate of at least 6% to 8% for patients with metastatic melanoma and renal cell carcinoma.