In this Phase II study, 76 patients with unresectable stage IV melanoma who were either chemotherapy na??ve or pretreated were given therapy. The treatment regimen consisted of nab-paclitaxel (100 mg/m2) and carboplatin (AUC 2) on days 1, 8 and 15 of a 28-day cycle until disease progression. SPARC in tumor biopsies was measured using a validated SPARC IHC. The primary objective was to use the developed SMS to distinguish between low risk and high risk groups with respect to PFS and OS. Tumor SPARC IHC data was available for 40 patients, suggesting that SPARC in the tumor microenvironment may play an important role in the outcome of melanoma patients:

A unique SPARC signature was developed for melanoma patients to distinguish early progressers (LR,> Plasma SPARC levels were higher in melanoma patients than normal controls (mean 300 ng/ml,> For the high-risk versus low-risk groups respectively, median PFS increased from 3.7 to 6.6 months and median OS increased from 9.4 to 17.7 months

III. Oblimersen one-hour IV infusion in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma (Abstract #8561)

In this ongoing Phase 2 study, 13 chemotherapy-na??ve advanced melanoma patients with an ECOG PS of 0-2 and baseline LDH greater than or equal to 1.1 x ULN have been treated. Therapy consisted of a 30-minute IV infusion of nab-paclitaxel (175 mg/m2) (days 4, 25), oral temozolomide (75 mg/m2) (days 1-42) and a 1-hour IV infusion of oblimersen (900 mg) (days 1, 4, 8, 11, 22, 25, 29, 32) on a 56-day cycle. The primary endpoint for this study is safety and efficacy, with responses evaluated based on RECIST criteria. Results included:

Three patients who progressed after one cycle Ten patients who are continuing treatment; one has demonstrated complete response, four have demonstrated partial response (PR), four have stable disease (SD), and one has yet to be evaluated for response One patient with a PR demonstrated increased intra-tumoral caspase 3 and decreased Bcl-2 on day 4 due to an overall reduction in tumor burden, which correlated with a decrease in shed collagen epitopes and clinical response

Non-hematological toxicities were generally mild with one patient hospitalized for drainage of a pre-existing pleural effusion (grade 3), for which she had declined treatment prior to enrollment. No other Grade 3 or 4 events have occurred. Planned enrollment of 14 patients is continuing.

The results from these studies have not been formally reviewed by the Food and Drug Administration.

Source: Abraxis BioScience, Inc.