Sorafenib and pegylated interferon-α2b in advanced metastatic melanoma: a multicenter phase II DeCOG trial.

BACKGROUND: The combination of sorafenib, a multikinase inhibitor, and pegylated interferon-α2b (Peg-IFN-α2b) could potentially lead to an improved antitumoral response. Previously, combinations of interferon and sorafenib have been used in renal cell cancer. PATIENTS AND METHODS: Patients with stage IV metastatic melanoma and no previous systemic therapies apart from adjuvant immunotherapy received Peg-IFN-α2b 3 µg/kg once per week, and sorafenib 400-mg b.i.d. for a minimum of 8 weeks. The primary study end point was disease control rate (DCR). RESULTS: Between February 2008 and February 2009, 55 patients were enrolled with a median age of 64 years (20-85). At 8 weeks, 2 patients (3.6%) had a partial response (PR) and 14 patients a stable disease (25.5%), for a DCR of 29.1% in the intention-to-treat (ITT) population. The median progression-free survival in the ITT population was 2.47 months (95% confidence interval 1.22-3.72 months). The toxicity of sorafenib and Peg-IFN-α2b combination was characterized by mainly hematological side-effects, including one treatment-related bleeding complication with a fatal outcome. Other grade 3/4 toxic effects were fatigue and flu-like symptoms. CONCLUSION: The combination of sorafenib and Peg-IFN-α2b showed modest clinical activity and some serious side-effects including fatal bleeding complications.

Clinicopathologic prognostic markers of survival: an analysis of 259 patients with malignant melanoma >or=1 mm.

The histopathologic status of the sentinel node (SN) and the ulceration of the primary tumor are important indicators of the clinical outcome of melanoma patients. The purpose of this study was to investigate potential correlations between prognostic factors and the sentinel lymph node status as well as their influence on disease-free survival (DFS), distant metastases-free survival (DMFS), and overall survival (OS). The medical records of 259 melanoma patients who underwent sentinel lymph node dissection between 2000 and 2006 were analyzed. DFS, DMFS, and OS were assessed. A uni- and a multivariate analysis to determine prognostic factors were performed. Histologic type, Clark's level, and Breslow's tumor thickness were the only parameters that showed a significant correlation with a positive SN. The univariate analysis revealed SN positivity (DFS and DMFS: p < 0.001; OS: p = 0.039) and ulceration (DFS: p < 0.001; DMFS: p = 0.001; OS: p = 0.003) to be significant prognostic markers. However, ulceration was the only independent prognostic factor for OS that was upheld by the multivariate analysis (p = 0.006; HR 3.89; CI 1.48-10.27). In stage I/II melanoma patients, ulceration of the primary tumor was the strongest prognostic factor for RFS, DMFS, and OS and superior to the pathology status of the SN.

Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG).

BACKGROUND: Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNalpha-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation. PATIENTS AND METHODS: In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 mug peg-IFNalpha-2b s.c. per week and oral TMZ 200 mg/m(2) (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety. RESULTS: In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%. CONCLUSIONS: The efficacy of TMZ plus peg-IFNalpha-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNalpha-2b seems to be similar to non-peg-IFN when combined with TMZ.

Risk evaluation in cutaneous melanoma patients undergoing lymph node dissection: impact of POSSUM.

INTRODUCTION: When lymphatic metastasis occurs, surgery is the primary treatment modality in melanoma patients. Depending on the tumour stage, patients receive a completion lymph node dissection (CLND) when a positive sentinel node is detected. Patients with clinically evident disease of the regional lymph nodes are recommended to undergo a therapeutic lymph node dissection (TLND). The aim of this study was to assess the morbidity of CLND and TLND and to evaluate the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) for preoperative risk adjustment of postoperative morbidity. METHODS: The hospital files of 143 patients who underwent CLND and TLND for malignant melanoma were analysed. The POSSUM score was used to predict morbidity rates after surgery for the total patient group as well as separated for CLND and TLND patients. RESULTS: The overall complication rate was 28.0% and the mortality rate was 0%. The morbidity rate predicted by POSSUM was 32.9%, the mortality 8.3%. Morbidity in patients undergoing CLND was significantly higher with regard to overall wound complications compared with patients with TLND. In these subgroups, POSSUM failed to predict the rates precisely. CONCLUSIONS: The POSSUM score predicted the morbidity of the total patient group accurately but failed to predict the rates in the TLND and CLND subgroups. Patients receiving CLND showed the highest morbidity rates. Preoperative sentinel lymph node biopsy therefore has more influence on postoperative morbidity than the physiological parameters represented in the POSSUM physiological score.