Phase I trial of PEG-interferon and recombinant IL-2 in patients with metastatic renal cell carcinoma

Purpose Pegylated interferon α-2b (PEG-Intron ® ) is a conjugate of polyethylene glycol (PEG) and interferon alpha-2b, has a prolonged half-life, and an increased area under the curve (AUC) for interferon α-2b. The combination of PEG-Intron ® with recombinant interleukin-2 (rIL-2) was investigated in a phase 1 trial. To determine the maximal tolerable dose (MTD) and preliminary efficacy of concurrent subcutaneous (SC) administration of PEG-Intron ® and rIL-2 in patients with metastatic renal cell carcinoma (RCC). Methods Cohorts of 3–6 patients received escalating doses of PEG-Intron ® (I-1.5, II- 1.5, III-3.0, IV-3.0, V-4.5 μg/kg SC) given weekly in combination with rIL-2 administered three times weekly (TIW) for 6 weeks. rIL-2 dose levels were escalated in weeks 1 and 4 (I-10.0, II-15.0, III-15.0, IV-20.0, V-20.0 MIU/m 2 SC), and 5.0 MIU/m 2 SC TIW was administered during weeks 2, 3, 5 and 6. Results Thirty-four patients (24 men; 10 women) were accrued at dose levels I ( n = 4), II ( n = 4), III ( n = 6), IV ( n = 14), and V ( n = 6) between October 2000 and October 2002. All but one patient had prior nephrectomy ( n = 33) and all but one patient (97%) had received no prior systemic therapy. Patients received a median of four cycles of treatment (range 1–9). Dose limiting toxicity occurred at dose level V and included grade 4 neutropenia and hypoxemia. A partial response was found in 5 pts (15%). Median progression-free and overall survival were 9.0 (95% C.I. 5.6–13.1 months) and 31.9 months (95% C.I. 17.2–61.9 months), respectively. Conclusion The combination of PEG-Interferon and SC rIL-2 can be administered with acceptable toxicity.