Hope For Cancer

Results from two Phase III clinical trials suggest that the addition of the targeted therapy Avastin® (bevacizumab) to chemotherapy delays the progression of advanced ovarian cancer but may not improve overall survival. These results were published in the New England Journal of Medicine.

Each year in the United States, roughly 22,000 women are diagnosed with ovarian cancer and more than 15,000 die of the disease. Treatment for ovarian cancer commonly involves surgery and/or chemotherapy, but outcomes for women diagnosed with advanced disease remain poor, and researchers continue to evaluate new approaches to treatment.

Avastin is a targeted therapy that blocks a protein known as VEGF. VEGF plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Currently, Avastin is used for the treatment of selected patients with lung cancer, colorectal cancer, kidney cancer, or glioblastoma.

The role of Avastin in ovarian cancer was evaluated in two Phase III clinical trials that were recently published in the New England Journal of Medicine. The first study enrolled 1873 women with newly diagnosed Stage III or Stage IV ovarian cancer.[1] After surgery, women were assigned to one of three treatment groups: 1) chemotherapy alone; 2) chemotherapy plus Avastin; and 3) chemotherapy plus Avastin followed by up to 10 months of additional treatment with Avastin alone.

• Avastin delayed cancer progression: survival without cancer progression was 10.3 months among women treated with chemotherapy alone, 11.2 months among women treated with chemotherapy and Avastin, and 14.1 months among women treated with chemotherapy and Avastin followed by additional Avastin.
• Overall survival was similar in the three study groups.
• Side effects that were more common in the Avastin groups included high-blood pressure that required treatment and gastrointestinal perforation.

In a second study, researchers evaluated Avastin among 1,528 women with high-risk or advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer.[2] Study participants were treated with chemotherapy with or without Avastin. Women in the Avastin group continued Avastin treatment after chemotherapy was completed.

• The addition of Avastin delayed cancer progression: survival without cancer progression was 21.8 months among women treated with Avastin and chemotherapy, compared with 20.3 months among women treated with chemotherapy alone.
• The benefit of Avastin appeared to be greater for the subset of women at high risk of progression.
• Final information about overall survival is not yet available.

Taken together, these two studies suggest that Avastin given during chemotherapy and for several months afterwards delays the progression of ovarian cancer compared with chemotherapy alone. Avastin increases side effects, however, and may not improve overall survival. Additional research may clarify whether certain subgroups of ovarian cancer patients are more likely than others to benefit from Avastin.

References:

[1] Burger RA, Brady MF, Bookman MA et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. New England Journal of Medicine. 2011;365:2473-83.

[2] Perren TJ, Swart AM, Pfisterer J et al. A phase 3 trial of bevacizumab in ovarian cancer. New EnglandJournal of Medicine. 2011;365:2484-96.

…source …more about ovarian cancer

Research led by Shyamal Desai, PhD, Assistant Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, has discovered a key change in the body’s defense system that increases the potential for breast cancer to spread to other parts of the body. The results, reported for the first time, are featured in the January 2012 issue of Experimental Biology and Medicine.

For cancer cells shape matters. All cells contain a protein cytoskeleton that acts as a scaffold determining overall shape and function, the position of the cell within an organ or tissue, and the ability of the cell to communicate with its neighbors to prevent the uncontrolled growth typical of cancer cells. However, cell transformations that result in cancer disrupt the genetic programs of the cell and alter the cytoskeleton, leading to changes in shape, function, and cell communication that produce uncontrolled growth and metastatic spreading of the tumor. Understanding these changes to the normal genetic program of a cell and the consequences that ultimately lead to cancer have been major challenges to cancer biologists.

This research, funded by the National Institutes of Health, found that a cellular defense system called the ISG15 pathway, which is normally involved in fighting bacterial and viral infection, is triggered in breast cancer to disrupt normal cytoskeletal function and increase the possibility that the cancer cells will metastasize, or spread.

“Our findings, for the first time, causally link an alteration in the ISG15 pathway during transformation with metastatic potential,” notes Dr. Shyamal Desai, Assistant Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, “thus providing a novel therapeutic target for future drug discovery.”

Cells contain a protein quality control pathway termed the Proteasome that breaks down damaged and unneeded proteins to their component amino acids for recycling. Such proteins are marked for degradation by flagging them with a small protein called Ubiquitin, which is then recognized by the Proteasome. Alterations in the genetic program that controls the Ubiquitin/Proteasome system have been known for some time to cause cell transformation and cancer. More recently, Dr. Desai and her colleagues have demonstrated that, unlike normal cells, transformed cancer cells produce increased amounts of a related control system that marks proteins with another small protein called ISG15.

Previous research reports that the amount of ISG15 is increased in high-grade compared with low-grade cancers. The ISG15 system is normally activated by interferon and is part of an ancient cellular immune response designed to counter bacterial and viral infection. By a still unidentified mechanism, cancer cell transformation activates the ISG15 pathway. Dr. Desai and colleagues have previously reported that activation of the ISG15 system interferes with function of the Ubiquitin/Proteasome pathway. In their latest work, Dr. Desai and colleagues show that several key proteins that regulate cell movement, invasion, and metastasis are blocked from Proteasome degradation by the ISG15 system and that genetic manipulation to inhibit this pathway reverses cancer cell transformation, suggesting an approach to blocking cancer progression. …source …more about breast cancer

For multiple myeloma patients who relapse after initial treatment with an autologous stem cell transplant, salvage treatment with a second autologous stem cell transplant appears to be safe and to produce response rates that are similar to other treatment options. These results were published in Cancer.

Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine.

High-dose cancer treatment followed by a stem cell transplant may be used in the treatment of several types of hematologic cancers, including multiple myeloma. Stem cell transplants may use the patient’s own stem cells that were collected prior to cancer treatment (an autologous transplant) or stem cells donated by another person (an allogeneic transplant).

For multiple myeloma patients who relapse after initial treatment with an autologous stem cell transplant, the effects of a second (salvage) autologous transplant have been uncertain. To explore this question, researchers conducted a study among 44 myeloma patients (median age of 54) who had relapsed and been treated with a second autologous stem cell transplant. The interval between the first and second transplant ranged from two to 78 months (median interval was 2.6 years).

Forty-one percent of patients received maintenance therapy after the second transplant.

• Roughly one-quarter of the patients experienced severe (grade 3 or worse) non-blood-related side effects. There was one treatment-related death.
• 11 percent of patients had a complete response or a near-complete response to salvage treatment, and 79% had a partial response.
• Median time to progression after salvage treatment was just over a year. Overall survival was 2.6 years.

These results suggest that for selected myeloma patients, treatment of a relapse with a second autologous stem cell transplant is an option.

Reference: Shah N, Ahmed F, Bashir Q et al. Durable remission with salvage second autotransplants in patients with multiple myeloma. Cancer. Early online publication November 15, 2011. …source …more about myloma