Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma

Abstract

A double-institution phase II study was performed in patients with metastatic renal cell carcinoma treated subcutaneously (s.c.) with interleukin 2 (IL-2) and alpha-interferon (INF-alpha). Thirty-eight patients were treated over a course of 7 weeks. Initially (day 1 + 2) patients received s.c. IL-2 at 18 x 10(6) IU m-2. During the following 6 weeks, patients received s.c. IL-2 at 3.6 x 10(6) IU m-2 for 5 days per week and s.c. INF-alpha at 5 x 10(6) for 3 days per week. Thirty-eight patients were evaluated for response. An objective response was seen in seven patients (18.4 +/- 12.3%), with one complete response and six partial responses. Median duration of response was 6.7 months. Toxicity could be evaluated in 38 patients and was limited. Mild to moderate toxicity included fever (97%), fatigue or malaise (76%), nausea or vomiting (50%), anorexia (32%), hypotension (26%), neurological disturbances (26%) and hypercreatininaemia (39%). In addition, four grade IV haematological toxicities were noted. No cardiac side-effects were seen. IL-2 and INF-alpha given by this schedule can be safely administered in an outpatient setting. The objective response rate was similar to our previous treatments with high-dose IL-2 given as a continuous infusion.

Subcutaneous interleukin-2, interferon alpha-2b and 5-fluorouracil in metastatic renal cell carcinoma as second-line treatment after failure of previous immunotherapy: a phase II trial

“…As first-line treatment, IFNa and IL-2 have shown objective responses in 18% of patients included into trials that we conducted Ravaud et al, 1994); we planned to detect a response rate X10%. We assessed the response rate after 29 patients had been recruited to have a 95% chance of detecting at least one response when the actual response rate was X10%.…”

Optimal regimes for local IL-2 tumour therapy

“…Many studies have been performed to improve the results and/or reduce treatment-related toxicity. In both experimental tumour models and human cancer patients it has been shown that S.C. or regional IL-2 administration results in better tolerance of the treatment without apparent loss of therapeutic efficacy (Ottow et al, 1987;Steis et al, 1990;Vaage, 1991;Sleijfer et al, 1992;Ravaud et al, 1994;Sone and Ogura, 1994). Also, evidence is accumulating that doses of less than 10% of the maximum tolerated dose are therapeutically effective (Cortesina et Bruton and Koeller, 1994;Yang et al, 1994).…”

Targeted Approaches for Treating Advanced Clear Cell Renal Carcinoma

“…The median duration of a partial response (PR) is 12-19 months. Combinations of IFN-α and IL-2 show the same response rates as both cytokines alone [23][24][25][26][27][28][29]. In a large phase III study no survival benefit was detected for patients being treated with the combination as compared to both cytokines alone [22].…”