Two investigator initiated studies evaluating the benefits of a combination therapy of Abraxane? (paclitaxel albumin-bound particles; Celgene International S?rl), a solvent-free chemotherapy treatment which combines paclitaxel with albumin, a naturally-occurring human protein, and bevacizumab (Avastin?, Genentech/Roche) in unresectable melanoma were presented at the 47th annual meeting of the American Society of Clinical Oncology in Chicago.

Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment called melanin which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye (uveal melanoma). Melanoma can occur in any part of the body that contains melanocytes.

Melanoma is less common than other skin cancers. However, it is much more dangerous and causes the majority (75%) of deaths related to skin cancer. Worldwide, doctors diagnose about 160,000 new cases of melanoma yearly. The diagnosis is more frequent in women than in men and is particularly common among Caucasians living in sunny climates, with high rates of incidence in Australia, New Zealand, North America, and northern Europe. According to a WHO report about 48,000 melanoma related deaths occur worldwide per year.

Two Studies
In the first study, patients were given either abraxane (100 mg/m2) on days 1, 8 and 15 carboplatin (AUC 6 IV) on day 1 and bevacizumab (10 mg/kg IV) on days 1 and 15, each of a 28 day cycle (n=51); or temozolomide (Temodar,? Merck & Co) (200 mg/m2) on days 1-5 and bevacizumab (10 mg/kg IV) on days 1 and 15 of a 28 day cycle (n=42). The two arms were run independently. Starting doses were reduced following an addendum to the study: abraxane was lowered to 80 mg/m2 and carboplatin to AUC 5. For both arms, 6-month progression-free survival rate was the primary endpoint.

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Survival rates
After a median 4-cycles of therapy (range 1-27+), the 6-month progression free survival (PFS) rate for patients in the abraxane arm was 54.9% (95% CI; 42.8%-70.4%) and the one-year PFS rate was 27.5% (95% CI: 17.6%-42.9%). Median PFS for patients in the Abraxane arm was estimated to be 6.6 months and the median overall survival (OS) was estimated to be 13.9 months. The 12-month survival rate was 58.1% (95% CI: 45.9%-73.6%). The confirmed response rate was 33.3%.

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In the temozolomide arm, patients received a median 4-cycles of therapy (range 1-30+). The 6-month PFS rate was 32% (95% CI; 20.5-50.1%). Median PFS for patients in the temozolomide arm was estimated at 3.8 months and the median OS was 12.3 months.

The most common grade 3 or higher adverse events in the abraxane arm (following addendum) were neutropenia (43%), leukopenia (26%), thrombocytopenia (17%) and anemia (17%). In the temozolomide arm, the most common grade 3 or higher adverse events were vomiting (12%), fatigue (10%), leukopenia (10%) and neutropenia (10%).

Second study results
In the second, single-arm study, patients received abraxane (150 mg/m2) on days 1, 8 and 15, and bevacizumab (10mg/m2) on days 1 and 15 of a 28-day cycle (n=50).

The PFS rate at 4 months, which was the primary endpoint of the study, was 73%. The median PFS for patients in the study was 7.63 months (95% CI: 5.56 to 9.93 months). The median overall survival was 16.8 months (95% CI: 11.3 to 20.7 months). The 12-month survival rate was 62% and the 2-year survival rate was 30%. The response rate was 36.0%.

In the study, the most common grade 3 or higher adverse events related to study drug were neutropenia (20%), neuropathy (14%), mucositis (8%) and fatigue (6%).

The results presented at ASCO are from investigational studies. At this time, abraxane is not approved as a treatment for melanoma. CA033, a phase III, pivotal study of abraxane versus DTIC for the initial treatment of over 500 patients with metastatic malignant melanoma is currently underway.

Clinical Trials:
[1]Cisplatin, Temozolomide, Abraxane, With Interleukin-2 and Interferon for Metastatic Melanoma (BCAA)
[2] Abraxane and Temodar Plus Genasense in Advanced Melanoma

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