8017 Background: Modifying the pharmacokinetic profile of IFN alfa-2b (PegIFN) may improve its activity and tolerability. Specifically, the conjugation of recombinant IFN alfa-2b with a 12 kDa polyethylene glycol (Peg) chain results in a prolonged half-life and has been previously demonstrated to increase efficacy in hepatitis C patients compared to nonpegylated IFNs. We therefore evaluated the combination of TMZ with PegIFN in stage IV metastatic melanoma. Methods: This open-label, phase II study was conducted by the DeCOG at 10 study sites. Eligible pts were between 18 and 75 yrs, had a histologically confirmed diagnosis of metastatic melanoma (stage IV AJCC), no brain metastases and no prior chemotherapy. Pts were required to have a Karnofsky score of > 60% as well as adequate renal, liver and bone marrow function. Informed consent from all participants and approval from the corresponding ethic committees was provided. The regimen (28 d cycles) consisted of TMZ (200 mg/m2 d 1–5) in combination with PegIFN (100 μg sc d 1, 8, 15 and 21). Patients received 2 cycles before reevaluation (WHO response criteria). OR and OS were primary and TTP and toxicity were secondary endpoints of the trial. Results: 124 pts were accrued between 10/02 and 7/04, 8 pts were ineligible or withdrew consent, and thus 116 pts were treated per protocol. At the time of data analysis, 81.0% of pts had died from melanoma and median follow up time was 9.4 months. OR was 18.1% (2 CR, 1.7%; 16 PR; 16.4%); 25.0% of pts presented with SD and 54.3 % progressed (2.6% not evaluable). Median TTP was 2.8 months, median OS 9.0 months (95% CI 7,4;10,6). Grade (gr) 3/4 leucopenia occurred in 22.8% and gr 3/4 thrombocytopenia in 20.3%. Gr 1/2 nausea and emesis experienced 37.5% of the pts; severe nausea (gr 3/4) was rare (1.7%). Liver enzyme elevation occurred in 30.5 % (26.3% gr 1/2; 4.2% gr 3). Conclusions: Combination therapy with TMZ and pegylated interferon alfa-2b constitutes a manageable treatment option in the outpatient setting for advanced metastatic melanoma. Its primary advantage is an increased patient convenience as a result of oral intake of TMZ and once weekly application of PegIFN. [Table: see text]
Safety, Tolerability, and Mechanisms of Antiretroviral Activity of Pegylated Interferon Alfa‐2a in HIV‐1–Monoinfected Participants: A Phase II Clinical Trial