By CancerConsultants.com
Patients with advanced melanoma experienced higher response rates and longer survival without cancer progression when treated with an experimental anticancer vaccine in addition to standard therapy. These were the preliminary findings from a Phase III clinical trial presented at the 2009 annual meeting of the American Society of Clinical Oncology (ASCO).
Patients with metastatic melanoma are usually treated with a combination of chemotherapy and immunotherapy. Chemotherapeutic agents with activity include dacarbazine, temozolomide, cisplatin, vinblastine, thalidomide, and docetaxel. Immunotherapy agents include interferon-alfa (INF-alfa) and Proleukin® (interleukin-2,IL-2). However, because most therapy is palliative, tolerability of treatment is a significant factor. Recently, researchers have emphasized the development of tolerable regimens.
Proleukin in high doses is an FDA-approved drug for the treatment of metastatic melanoma. However, Proleukin produces responses in only a minority of patients and at high doses is associated with significant toxicities. There have been innumerable studies performed over the past two decades to improve the response rate and decrease the toxicities of Proleukin-based regimens for the treatment of melanoma. Despite all of these efforts, biologic therapy or combined biologic and chemotherapy still benefit only a minority of patients with melanoma. Various vaccines have been tested in patients with melanoma, but none have been approved for this use by the U.S. Food and Drug Administration.
In the current study, researchers evaluated an experimental anticancer vaccine known as gp100:209-217(210M) peptide. The vaccine acts by stimulating T cells to attack melanoma cells. This study enrolled 185 patients with Stage IV or locally advanced Stage III melanoma. Study participants were assigned to receive treatment with Proleukin alone or with Proleukin plus the vaccine.
Follow-up is not yet complete, but the following results were presented at ASCO:
•The overall response rate was 22% for patients treated with Proleukin plus the vaccine compared with 9.7% for patients treated with Proleukin.
•Progression-free survival was 2.9 months among patients treated with IL-2 plus the vaccine compared with 1.6 months among patients treated with Proleukin alone.
•Overall survival was 17.6 months among patients treated with Proleukin plus the vaccine compared with 12.8 months among patients treated with Proleukin alone. The difference between groups in overall survival did not meet the criteria for statistical significance.
•The vaccine was well tolerated. Side effects were swelling and redness at the injection site.
Comments: This study is one of the first to show promising results for vaccine in metastatic melanoma. Researchers will continue to follow the patients enrolled in the study to assess longer-term results.
Reference: Schwartzentruber DJ, Lawson D, Richards J et al. A phase III multi-institutional randomized study of immunization with the gp100:209-217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. Journal of Clinical Oncology. 2009;27:15s, abstract CRA9011.
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Phase III Multi-Institutional Randomized Study of Immunization With the GP100: 209-217 (210M) Peptide Followed by High Dose IL-2 vs. High Dose IL-2 Alone in Patients With Metastatic Melanoma
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
•Whether the addition of peptide vaccine to high-dose aldesleukin is superior to alaldesleukin alone by response rates after each course of treatment [ Designated as safety issue: No ]
Secondary Outcome Measures:
•Toxicity of treatment by NCI Common Toxicity Criteria after each course of treatment [ Designated as safety issue: Yes ]
•Disease-free and progression-free survival comparison by disease evaluation every 3 months after treatment [ Designated as safety issue: No ]
•Immunologic response to treatment by various laboratory studies before and after each course of treatment [ Designated as safety issue: No ]
•Quality of life by Functional Assessment of Chronic Illness Therapy Fatigue Subscale RSF-36 SDS before and after the first course of treatment [ Designated as safety issue: No ]
Do you reconize the graph, you should . Now Look closely at the timing of the addition of IL-2. Do you see a major problem?????
It (IL-2) is being added before and close to the maximum propgation of the CD4+ T cells. This means they are growing the Tregs cells which we want to deplete or surpress.
VERY INTERESTING to say the Least...
Take care
Jimmy B
Melanoma_Missionary
Take Care,
Jimmy B
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