SAN FRANCISCO, Dec. 12 /PRNewswire/ -- A novel low-dose outpatient chemobiotherapy combination of temozolomide, the granulocyte macrophage colony stimulating factor (GM-CSF) LEUKINE(R) (sargramostim), Interferon-alpha-2b and interleukin-2 appears to be efficacious and well-tolerated in patients with inoperable stage IV metastatic melanoma, according to data published in the Journal of Clinical Oncology. In addition, the regimen appears to protect against the development of brain metastases.
“The impressive clinical response observed with this combination, achieved with a therapy that was a low-dose outpatient regimen that allowed for home dosing, is extremely encouraging given the dismal prognosis of patients with metastatic melanoma and poor response to currently available treatments,” said Lynn E. Spitler, M.D., study investigator and director of the Northern California Melanoma Center, San Francisco. “The suggested ability to protect against development of brain metastases is of particular significance, since brain metastases are largely responsible for chemobiotherapy treatment failures and death in patients with metastatic melanoma.
“There is no question that more-effective and less-toxic therapies for metastatic melanoma are desperately needed, and this regimen may offer some patients a promising and much-needed alternative to high-dose biochemotherapy regimens, which typically require hospitalization and are disruptive of lifestyle,” Dr. Spitler added.
These data are from a Phase 2, open-label, multi-center trial that assessed the efficacy and safety of low-dose outpatient chemobiotherapy in 31 patients with inoperable metastatic melanoma. Twenty-eight patients (90%) had M1c disease (metastases to the internal organs [viscera] or the presence of an elevated serum LDH level), and 58% had three or more sites of metastasis. Four patients (13%), all with M1c disease, had a complete response, and four patients had a partial response. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. Two patients (6%) developed CNS metastasis as the first site of disease progression, and seven (23%) of 30 experienced CNS progression after receiving chemobiotherapy. The treatment was generally well-tolerated.
About the Study
Thirty-one patients with histologically confirmed unresectable stage IV melanoma were enrolled in the study. Patients were permitted to have received therapy for prior disease but must have completed therapy at least one month before study entry. The patient population included two patients who had brain metastases that were considered controlled at study entry.
The treatment regimen consisted of temozolomide at 200 mg/m(2) (at 150 mg/m(2) daily for patients with a previous history of chemotherapy) given orally days one through five, followed by 12 days of subcutaneous daily biotherapy with LEUKINE at 125 mcg/m(2) to a maximum 250 mcg, Interferon-alpha-2b at 5 MU and interleukin-2 at 4 MU/m(2). This 28-day treatment cycle was repeated as clinically indicated with the same treatment sequence and dosage of each individual medication, or adjusted per-dosing modifications based on adverse events and the investigator’s judgment. Response and progression were evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
Four patients (13%) achieved a complete response and four had a partial response. The overall objective response rate was 26 percent (complete and partial response). An additional seven patients (23%) had stable disease for >4 months, bringing the overall rate of benefit to 48%. Twenty-nine patients (94%) experienced disease progression. The median duration of progression-free survival was 4.9 months. The overall progression-free rate was 29% at one year and 10% at two years. Twenty-six patients died (84%). The median duration of survival was 13.1 months for all patients and 25.9 months for patients experiencing an objective response. The overall survival rate was 52% at one year and 25% at two years. Median overall survival was 13.1 months, with 25% of patients achieving long-term survival (more than 2 years). Two patients developed CNS metastasis as the first site of disease progression, and 23 % of patients experienced CNS progression after receiving chemobiotherapy.
Toxicity occurred in 78% of the cycles and was grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles.
About Melanoma
Melanoma is characterized by the uncontrolled growth of pigment-producing tanning cells. Melanomas may suddenly appear without warning, but can also develop from or near a mole. More than one million new cases of skin cancer will be diagnosed in the United States this year. About 80 percent of the new skin cancer cases will be basal cell carcinoma, 16 percent are squamous cell carcinoma and four percent are melanoma. Melanoma is the fifth most common cancer in men and the sixth most common cancer in women.
Contact: Marybeth Quane 212.299.8972 Marybeth.Quane@zenogroup.com Smitha Dwarakanath 212-299-8981 Smitha.Dwarakanath@zenogroup.com
Lynn E. Spitler, M.D
CONTACT: Marybeth Quane, +1-212-299-8972, Marybeth.Quane@zenogroup.com, orSmitha Dwarakanath, +1-212-299-8981, Smitha.Dwarakanath@zenogroup.com
