Combined treatment with pegylated interferon–α‐2a and dacarbazine in patients with advanced metastatic melanoma

Abstract

BACKGROUND.Dacarbazine (DTIC) and pegylated interferon (IFN)–α‐2a have both demonstrated some efficacy as single agents in metastatic melanoma. To the authors' knowledge, the current study is the first to test a combination of these 2 agents in a phase 2 trial.METHODS.Twenty–eight patients with stage IV melanoma without brain metastases were treated with DTIC (at a dose of 850 mg/m2 every 3 weeks) combined with weekly pegylated IFN–α‐2a at a dose of 180 μg. The study was initiated to evaluate the efficacy and tolerability of the combination. The primary study endpoint was objective response.RESULTS.Twenty–five patients were evaluable for response. Two patients (8.0%) achieved a complete response that continued for >480 days and 746 days, respectively. Four patients (16.0%) demonstrated a partial response, and another patient experienced stable disease. Six of 7 nonprogressive patients had either not received treatment or had not developed disease progression during adjuvant IFN treatment for stage II/III disease. The median duration of response was 236 days, the median progression‐free survival was 56 days, and the overall survival time was 403 days. Few grade 3 toxicities and only 1 grade 4 toxicity were observed (according to National Cancer Institute Common Toxicity Criteria).CONCLUSIONS.The combination of DTIC and pegylated IFN–α‐2a was found to be well tolerated in patients with metastatic melanoma. The response rate of 24%, including 2 long‐lasting complete responses, is encouraging, but must be confirmed in larger trials. Cancer 2008. © 2008 American Cancer Society.

Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

“…In particular, it has been reported that the melanoma cell density in metastases and angiogenesis was significant reduced after a treatment with IFN-α [131] . melanoma without brain metastases have revealed that a combination of dacarbazine plus pegylated IFN-α2a was well tolerated and associated with a response rate of 24% in 25 patients evaluable for response, including 2 long-lasting complete responses [132] . Interestingly, the results of a phase II trial with an oncolytic herpes simplex virus type 1 encoding granulocyte macrophage-colony stimulating factor (GM-CSF), designated as Oncovex (GM-CSF), have also indicated a 28% objective response rate occurred in patients with melanomas which was accompanied by a tumor regression of both injected and non-injected lesions [126,127] .…”

Tumor Angiogenesis: Insights and Innovations

“…Many studies have used PEG IFN- α , a form of IFN- α that has been modified to have a longer half-life and thus have a greater opportunity to reduce angiogeneses [209]. A phase I trial completed tested the effect of subcutaneous injections of PEG IFN- α and recombinant IL-2 in patients with metastatic RCC [210].…”

“…A phase II trial then investigated the use of Dacarbazine (DTIC) alongside PEG IFN- α for the treatment of metastatic melanomas. Of the 25 patients who completed the study, 8% had complete remission from the treatment, while another 16% had partial responses [209]. Stable disease was found in 4% of patients while 72% had their disease progress.…”

Long-term pegylated interferon-α and its potential in the treatment of melanoma

“…117 Patients were treated with 850 mg/m 2 DTIC every 3 weeks combined with 180 μg PegIFNα-2α weekly. Only 50% of the patients participating in the study had received previous adjuvant therapy with IFN-α.…”

“…Median progression-free survival was 56 days, median duration of response was 236 days and OS time was 403 days. 117 Of interest is the fact that 6 out of 7 patients who showed CR or PR or developed SD had not received IFN adjuvant treatment in the past or progressed to stage IV melanoma during IFN treatment.…”