Background: In metastatic renal cell carcinoma, strictly immunomodulatory maneuvers using systemic interleukin-2 have produced objective tumor remissions and led to an effective palliation. The goals of an improved cost effectiveness and therapeutic index of interleukin-2 require the design of risk factor adapted individual therapeutic strategies for the outpatient setting.
Patients and methods: In 215 consecutive single institution patients with advanced metastatic renal cell carcinoma, the efficacy and tolerance of different subcutaneous recombinant interleukin-2 (rIL-2) based home therapies was assessed. Independent risk factors at pre-treatment level were identified and patient survival was compared between risk groups and therapies. Treatment consisted of s.c. rIL-2 alone and s.c. rIL-2 in combination with recombinant interferon-alpha 2 (rIFN-alpha 2), with or without intravenous 5-fluorouracil (5-FU).
Results: Overall objective response rate in 215 patients was 33% (95% confidence interval, 26 to 39%). Among patients receiving rIL-2 alone (n = 16), there was 1 partial remission (overall response, 6%). In patients on rIL-2 and rIFN-alpha 2 in combination (n = 79), 6 complete and 16 partial remissions occurred (overall response, 28%). Of 120 patients receiving a combination of rIL-2, rIFN-alpha 2 and 5-FU, 13 patients achieved a complete and 34 a partial remission (lung, liver, local relapse, bone, adrenal, pleural, and thyroid metastases; overall response 39%). Duration of complete and partial remissions ranged from 10 to 55+ months, and 3 to 32 months, respectively, in rIL-2/rIFN-alpha 2 treated patients, and from 8+ to 47+ months and from 3 to 31+ months, respectively, in rIL-2/rIFN-alpha/5-FU treated patients. Of all patients 5% achieved long-lasting remissions and remain disease-free. In the majority of patients, systemic toxicity of s.c. rIL-2 based protocols was limited to grade 1 or 2 constitutional symptoms i.e., fever, chills, malaise, and anorexia; this allowed for an outpatient therapy. No life-threatening toxicity and no toxic deaths occurred.
Conclusions: The present outpatient rIL-2 triple drug combination protocol was as effective as the most aggressive i.v. rIL-2 regimen available; it substantially improved the therapeutic index and cost effectiveness of rIL-2 therapy in metastatic renal cell carcinoma stratified for risk.