Targeted Therapy with Volociximab and DTIC Well Tolerated in Metastatic Melanoma

According to the results of a phase II clinical trial, volociximab (M200) in combination with DTIC (dacarbazine) is well tolerated in the treatment of metastatic melanoma. These results were presented at the 2006 annual meeting of the American Society of Clinical Oncology held in Atlanta, Georgia, June 2-6, 2006.

Melanoma is a type of skin cancer. Patients with metastatic (stage IV) melanoma have cancer that has spread from its site of origin to distant sites in the body. These patients cannot be cured with surgery alone and appear to benefit modestly from currently approved systemic therapies.

Although there are many choices of therapy for patients with metastatic melanoma, cancer still progresses in the majority of cases. Clinical response after treatment is, however, observed in 5-10% of patients with metastatic melanoma. These responses, some of which are long lasting, have generated optimism about treatment of this disease. Researchers continue to explore new approaches to the treatment of melanoma, including new targeted therapy and new combinations of drugs.

Volociximab is a type of targeted therapy called a monoclonal antibody that inhibits the activity of a protein found on cells that is involved in the formation of blood vessels. Inhibiting the formation of blood vessels essentially starves the cancer of the food and oxygen it requires to survive and grow.

The combination of velociximab plus DTIC was administered to 40 patients, half of whom had poor-prognosis stage IC melanoma. Median patient age was 58.8 years and 65% were male. This phase II clinical trial produced promising results:

Median progression-free survival was 72 days.
Median overall survival was 237 days.
More than half of patients (62%) experienced an anticancer response to treatment (defined as a partial anticancer response [3%] or stable disease [59%] at eight weeks after treatment).
The most common adverse events included nausea (50%), fatigue (43%), injection site irritation (30%), vomiting (30%), constipation (28%), arthralgia (20%), and diarrhea (20%). The two serious adverse events that were possibly related to volociximab were dyspnea (one patient) and deep vein thrombosis (one patient).

The researchers concluded that volociximab is well tolerated in combination with DTIC. Higher doses of volociximab are currently being evaluated.

Reference: Cranmer LD, Bedikian AY, Ribas A et al. Phase II Study of Volociximab (M200), an α5β1 Anti-integrin Antibody in Metastatic Melanoma. Proceedings of the 42nd annual meeting of the American Society of Clinical Oncology. Atlanta, GA. 2006. Abstract #8011.

Chemotherapy plus Immunotherapy May Not Improve Survival over Chemotherapy Alone in Metastatic Melanoma

According to an article recently published in the Annals of Oncology, the chemotherapy combination consisting of cisplatin, vindesine, and dacarbazine (CVD) produced similar delay of cancer progression and overall survival time as CVD plus the biologic agents interferon and interleukin.

Melanoma is a type of aggressive skin cancer that typically originates from a mole. Metastatic melanoma refers to cancer that has spread from its site of origin to distant sites in the body. Overall survival for metastatic melanoma remains unfavorable with standard therapies.

Melanoma is often non-responsive to chemotherapy and/or radiation therapy. Some research has indicated that stimulating the immune system to fight cancer with biologic agents such as interferon or interleukin improves outcomes. However, the use of biologic agents in the treatment of metastatic melanoma has not consistently shown improvements over other therapies.

To further evaluate the use of biologic agents in the treatment of metastatic melanoma, researchers from Italy and St Luke’s Episcopal Hospital in Houston, Texas, recently conducted a phase III clinical trial to directly compare different therapeutic regimens in patients with this disease.

This trial included 151 patients with metastatic melanoma who had not received prior therapy. Approximately half of the patients were treated with CVD, and the other half received CVD plus interferon and interleukin. Both groups experienced similar delay of cancer progression and overall survival times:

Anticancer responses were achieved in 21% of patients treated with CVD and 33% of patients treated with CVD plus interferon and interleukin.
Median time to cancer progression was identical between the two groups of patients.
Median overall survival was 12 months for those treated with CVD and 11 months for those treated with CVD plus interferon and interleukin.
At 52 months following initiation of therapy, 10% of patients were alive.
The researchers concluded that the addition of interferon and interleukin to CVD did not delay cancer progression or overall survival compared to CVD alone when used as initial treatment for metastatic melanoma. The authors stated that the addition of interferon and interleukin to CVD “cannot be recommended as standard first-line therapy for metastatic melanoma.”

It is important, however, for patients with metastatic melanoma to speak with their physician regarding their individual risks and benefits of the addition of biologic agents to their treatment regimen as previous studies have produced conflicting results.

Reference: Bajetta E, Del Vecchio M, Nova P, et al. Multicenter Phase III Randomized Trial of Polychemotherapy (CVD regimen) Versus the Same Chemotherapy (CT) plus Subcutaneous Interleukin-2 and Interferon-2b in Metastatic Melanoma. Annals of Oncology. 2006; 17: 571-577.

Melanoma Patients with Atypical Moles at High Risk of Additional Melanoma

According to an article recently published in the Archives of Dermatology, patients diagnosed with melanoma who have other atypical moles have a significantly increased risk of developing a subsequent melanoma and should continue close follow-up with a dermatologist.

Melanoma is a type of cancer that originates in cells of the skin. Melanoma is considered very deadly once it has spread past the site of origin. However, if melanoma is caught and treated prior to spread, cure rates are high. Typically, the treatment for melanoma that has not spread is surgical removal of the cancer and a surrounding area of healthy tissue.

Individuals with fair skin, freckles, a strong family history of melanoma and those who have spent a lot of time unprotected in the sun are advised to be screened regularly for melanoma by a dermatologist so that it may be caught and treated as early as possible.

Researchers continue to evaluate possible variables associated with an increased risk of developing melanoma so that patients at a higher risk of developing the disease may undergo more frequent monitoring to detect and treat the melanoma prior to spread.

Researchers from Dartmouth-Hitchcock Medical Center in New Hampshire recently evaluated data among patients diagnosed with an initial site of melanoma. The data included 354 patients who had been diagnosed with melanoma. Patients were followed to determine rates of possible subsequent sites of melanoma.

6% of patients developed a second site of melanoma within one year of the first melanoma diagnosis.
8% of patients had developed a second site of melanoma within two years of the first diagnosis.
Patients with atypical moles (non-cancerous changes in cells as determined by laboratory processes) had a significantly higher risk of subsequent melanoma.
Patients with three or more atypical moles had more than a four-fold increased risk of developing multiple subsequent melanomas compared to those with no atypical moles.
The researchers concluded that patients diagnosed with melanoma who have sites of atypical moles have a significantly increased risk of developing subsequent melanomas within the first couple of years following initial diagnosis. These patients should undergo frequent skin examinations by a dermatologist to detect and treat subsequent melanomas in their earliest stages.

Reference: Titus-Ernstoff L, Perry A, Spencer S, et al. Multiple Primary Melanoma - Two-Year Results From a Population-Based Study. Archives of Dermatology. 2006; 142: 433-438.

Immune Stimulating Vaccine Promising in Metastatic Melanoma

According to a recent article published in the journal Cancer, surgical removal of cancer spread in the body followed by peptide vaccines appear to significantly improve survival in some patients with metastatic melanoma.

Melanoma is a type of skin cancer that often starts in the form of a mole. Although melanoma is very curable in its earliest stages prior to its spread, advanced-stage melanoma is considered difficult to cure. Metastatic melanoma refers to cancer that has spread to distant sites in the body.

Long-term survival for this stage of disease remains dismal, with the median overall survival being 7 to 9 months. For some patients, the surgical removal of cancer sites that have spread in the body (metastasectomy) has improved survival. Furthermore, the use of immune therapy, or therapy that stimulates the immune system to attack the cancer, has also demonstrated an improvement in survival; however, these improvements remain suboptimal.

Several vaccines designed to stimulate a patient’s immune system to work against melanoma cancer cells are being evaluated in clinical trials. Many of these vaccines are in early-phase clinical trials and are still being refined to produce optimal and durable anticancer responses.

Researchers from the University of California Los Angeles (UCLA) recently evaluated data from five clinical trials that included patients with metastatic melanoma. These trials included 41 patients who underwent metastatectomy followed by specific vaccines that included proteins from cancer cells as well as an immune stimulating agent referred to as Montanide ISA 51.

At a median follow-up of 5.6 years, these results were recorded:

The median overall survival for these patients was nearly 4 years.
At 5 years, 45% of the patients were still alive.
The researchers concluded that metastatectomy followed by immune stimulating vaccines appears to provide promising survival in patients with metastatic melanoma. However, the researchers caution that these trials included small numbers of patients. In addition, these patients were able to have their sites of cancer surgically removed.

Patients with metastatic melanoma may wish to speak with their physician regarding their individual risks and benefits of metastatectomy and the participation in a clinical trial further evaluating vaccines or other novel therapeutic approaches. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov) and www.cancerconsultants.com.

Reference: Tagawa S, Cheung E, Banta W, et al. Survival Analysis after Resection of Metastatic Disease Followed by Peptide Vaccines in Patients with Stage IV Melanoma. Cancer. 2006; 106: 1353-1357.

Autoimmunity During Interferon Treatment for Melanoma Linked with Improved Survival

Among patients receiving immunotherapy for melanoma, those who showed evidence of autoimmunity (an immune response against the body’s own tissues) survived significantly longer than those who did not. These results were published in the New England Journal of Medicine.

Melanoma is a type of skin cancer that typically begins in the form of a mole. Stage II and stage III melanoma refer to melanoma that has spread from its site of origin to deeper tissue layers or nearby lymph nodes, but not to distant sites in the body.

Standard treatment for stages II-III melanoma typically includes surgery to remove the cancer, with or without immunotherapy. Immunotherapy refers to treatment that stimulates the immune system to fight cancer. Melanoma appears particularly responsive to immunotherapy.

Interferon alfa-2b is a type of immunotherapy. Though treatment with this agent has been shown to improve survival in patients with melanoma, common side effects include fatigue, fever, joint pain, and liver problems. Furthermore, only a subset of patients appears to benefit from treatment. In order to provide more individualized melanoma treatment, researchers continue to explore ways to identify those patients most likely to respond to immunotherapy. Patients who are unlikely to respond could be spared the toxic effects of treatment.

Interferon alfa-2b induces autoimmunity in some patients. In autoimmune conditions, the immune system attacks the body’s own tissues. In order to determine whether the development of autoimmunity following treatment with interferon alfa-2b is linked with response to treatment, researchers in Greececonducted a study among 200 patients with stage IIB, stage IIC, or stage III melanoma.

All patients were treated with interferon alfa-2b. Autoimmunity was defined as the subsequent development of antibodies against the body’s own tissues, or signs of autoimmunity such as vitiligo (a skin disorder).

After a median follow-up of 46 months, 115 patients experienced a cancer recurrence and 82 patients died.

Signs of autoimmunity were identified in 52 patients (26%). Patients with evidence of autoimmunity experienced significantly better survival than patients without evidence of autoimmunity:

Among the 148 patients without autoimmunity, 73% developed a cancer recurrence and 54% died.
Among the 52 patients with autoimmunity, 13% developed a cancer recurrence and 4% died.
The researchers conclude that evidence of autoimmunity during treatment with interferon alfa-2b is linked with improved overall survival and improved survival without cancer recurrence in patients with melanoma.

Reference: Gogas H, Ioannovich J, Dafni U et al. Prognostic Significance of Autoimmunity During Treatment of Melanoma with Interferon. New EnglandJournal of Medicine . 2006;354:709-718.