Phase II trial of interleukin 2, interferon alpha, and 5-fluorouracil in metastatic renal cell cancer: A Cytokine Working Group study

The purpose of this study was to evaluate the potential efficacy of alterna ting two outpatient regimens for the treatment of metastatic renal cell can cer. These regimens consisted of 4 weeks of recombinant interleukin 2 (rIL- 2) plus IFN-alpha 2B followed by 4 weeks of 5-fluorouracil plus IFN-alpha 2 B. Fifty patients meeting eligibility criteria of previous Cytokine Working Group studies were treated on an outpatient basis. Patients received s.c. rIL-2 (Proleukin; Chiron, Emeryville, CA) during weeks 1-4 of the 8-week re gimen. During weeks 1 and 4, the dosage for rIL-2 was 10 MIU/m(2) twice dai ly on days 3-5, and the dosage for IFN-alpha 2B (Intron; Schering Plough, K enilworth, NJ) was 6 MIU/m2 on day 1. During weeks 2 and 3, the dosage for rIL-2 was 5 MIU/m(2) on days 1, 3, and 5, and the dosage for IFN-alpha 2B w as 6 MIU/m(2) on days 1, 3, 5. During weeks 5-8, 5-fluorouracil (750 mg/m(2 )) was administered once weekly by i.v. infusion, and IFN-alpha 2B (9 MIU/m (2)) was administered as a s.c. injection three times weekly. Throughout th e treatment, an assessment of quality of life was made and a symptom-distre ss scale was evaluated. There were two patients with complete responses (CRs) and seven with partia l responses (PRs) for an objective response rate of 18% (95% confidence int erval, 10-25). The median response duration was 8 months (range, 3-51+ mont hs). The CRs lasted 5 months and 51+ months and the PRs ranged from 3+ to 1 8 months. After completing at least one course of treatment, eight patients (three with PR, one with minor response, four with stable disease) became CRs after surgery for remaining metastatic disease. Six remain alive at 43 to 53+ months, and 5 remain disease-free since surgery. The median surviva l of the study group is 17.5 months, with a maximal follow-up of 53+ months . The range in survival is 1-53+ months. Toxicity was primarily constitutio nal. and treatment modifications were designed to maintain toxicity at grad e 2/3. The most common toxicities during treatment with IL-2/IFN were fatig ue, nausea/vomiting, anorexia, skin reaction, diarrhea, fever, and liver en zyme elevations. One-third had central nervous system toxicity (headache, d epression, insomnia), During 5FU/IFN treatment, 49 of 50 patients experienc ed grade 2/3 myelosuppression during course 1. Eight patients experienced g rade 4 toxicities. In conclusion, the activity of this alternating regimen is similar to that of IL-2/IFN alone, given in 4-week cycles. The addition of 5FU/IFN failed to increase the efficacy and added new toxicity (myelosup pression). This report does not confirm the results previously reported for either alternating or simultaneous administration of these three agents. B ecause 5FU does not appear to add to the antitumor activity of IL-2-based t herapy for renal cancer, current efforts are directed toward a Phase III ra ndomized comparison of high-dose i.v. bolus inpatient IL-2 treatment versus treatment with outpatient s.c. injection of IL-2 plus IFN.