Chemotalk Newsletter, Vol. 68: December 1, 2013
Hello, Everyone ...
End of the year, and I'm trying something new.
I've attached a piece that appeared on a site that focuses on oncology. As interesting as the article was to me, the response to my comment was just as interesting, and even a little perplexing. First and foremost, I'm a patient. The one person who has been in dialogue with me online is very much pro-340B, and suggests that the problems that exist with the program have to do with a lack of clarification of the rules, and this issue is under the purview of a federal organization, Health Resources and Services Administration. I never heard of this entity before, but you can be sure I'm going to find out what they're doing to "clarify the rules", as my contact suggests.
I see cancer treatment as many others do, through the lens of someone who has had treatment and may need it again. I would very much appreciate any feedback on this issue. * * *
FDA APPROVES IBRUTINIB FOR MANTLE-CELL LYMPHOMA
The US Food and Drug Administration has approved ibrutinib (Imbruvica) for the treatment of patients with MANTLE-CELL LYMPHOMA, an aggressive and rare blood cancer, who have received at least one prior therapy. The new drug is an oral inhibitor of Bruton¹s tyrosine kinase, a crucial signaling molecule in the B-cell receptor pathway that has been shown to cause cell death and to lower the rate of movement of cancerous B cells.
MCL accounts for about 6% of all NON-HODGKIN LYMPHOMA cases in the United States, often presenting at an advanced stage where the disease has spread to the lymph nodes, bone marrow, and other organs.
³Imbruvica¹s approval demonstrates the FDA¹s commitment to making treatments available to patients with rare diseases,² said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA¹s Center for Drug Evaluation and Research. ³The agency worked cooperatively with the companies to expedite the drug¹s development, review, and approval, reflecting the promise of the Breakthrough Therapy Designation program.²
The trial that led to the accelerated approval of ibrutinib for MCL included 111 patients. Ibrutinib was administered daily until either disease progression or until adverse events became intolerable. Ibrutinib had an overall response rate of 66%. Improvement in survival has not yet been established.
Most of the adverse events in the trial were low-grade, including diarrhea, fatigue, nausea, anemia, neutropenia, edema, dyspnea, bruising, constipation, upper respiratory tract infection, rash, abdominal pain, vomiting, and decreased appetite. High-grade pneumonia occurred in 6% of patients. High-grade hematological events included thrombocytopenia and anemia. Four patients suffered from subdural hematomas, but all four patients had factors that put them at risk for such an event, including anticoagulant and antiplatelet therapies. Other adverse events include kidney problems, bleeding, infections, and the development of other cancer types.
Ibrutinib is the third drug approved to treat MCL. The FDA approved bortezomib in 2006 and lenalidomide in 2013.
Following the recent approval of obinutuzumab (Gazyva) for chronic lymphocytic leukemia, ibrutinib is now the second approved drug to have received a breakthrough therapy designation from the FDA. The designation can be used when preliminary evidence indicates a drug may offer a substantial improvement over current therapies for serious or life-threatening diseases.
* * * This is HUGE!:
50% OF PATIENTS IN CEDARS-SINAI BRAIN CANCER STUDY ALIVE AFTER 5 YEARS
With standard care, median length of survival is 15 months after diagnosis of GLIOBLASTOMA MULTIFORME -- and only 10 percent survive more than 5 years.
LOS ANGELES (NOV. 23, 2013) Eight of 16 patients participating in a study of an experimental immune system therapy directed against the most aggressive malignant BRAIN TUMORS glioblastoma multiforme survived longer than five years after diagnosis, according to Cedars-Sinai researchers, who presented findings at the Fourth Quadrennial Meeting of the World Federation of Neuro-Oncology.
Seven of the 16 participants still are living, with length of survival ranging from 60.7 to 82.7 months after diagnosis. Six of the patients also were "progression free" for more than five years, meaning the tumors did not return or require more treatment during that time. Four participants still remain free of disease with good quality of life at lengths ranging from 65.1 to 82.7 months following diagnosis. One patient who remained free of brain cancer for five years died of LEUKEMIA.
The original clinical trial a Phase I study designed to evaluate safety included 16 patients with glioblastoma multiforme enrolled between May 2007 and January 2010 by researchers at Cedars-Sinai's Johnnie L. Cochran, Jr. Brain Tumor Center. Results published in January at the end of the study showed median overall survival of 38.4 months. Typically, when tumor-removal surgery is followed by standard care, which includes radiation and chemotherapy, median length of survival is about 15 months. Median progression-free survival the time from treatment to tumor recurrence was 16.9 months at study's end. With standard care, the median is about seven months.
The experimental treatment consists of a vaccine, ICT-107, intended to alert the immune system to the existence of cancer cells and activate a tumor-killing response. It targets six antigens involved in the development of glioblastoma cells.
According to information presented at the scientific meetings, all eight long-term survivors had tumors with at least five antigens, 75 percent had tumors with all six, and 100 percent had tumors with at least four antigens associated with cancer stem cells cancer-originating cells that appear to enable tumors to resist radiation and CHEMOTHERAPY and even regenerate after treatment.
"Our findings suggest that targeting antigens that are highly expressed by cancer stem cells may be a viable strategy for treating patients who have glioblastomas. Long-term remission of disease in this group of patients was correlated with the expression of cancer stem cell tumor-associated antigens," said Surasak Phuphanich, MD, director of the Neuro-Oncology Program at the Cochran Brain Tumor Center and professor of neurology with Cedars-Sinai's Department of Neurosurgery and Department of Neurology.
Based on results of the Phase I study, the ICT-107 vaccine entered a Phase II multicenter, randomized, placebo-controlled trial in 2011.
The vaccine is based on dendritic cells, the immune system's most powerful antigen-presenting cells those responsible for helping the immune system recognize invaders. They are derived from white blood cells taken from each participating patient in a routine blood draw. In the laboratory, the cells are cultured with synthetic peptides of the six antigens essentially training the dendritic cells to recognize the tumor antigens as targets. When the "new" dendritic cells in the vaccine are injected under the patient's skin, they are intended to seek and destroy lingering tumor cells. Vaccine is administered three times at two-week intervals after standard radiation and chemotherapy.
ICT-107 is a product of the biotechnology company ImmunoCellular Therapeutics, Ltd. Cedars-Sinai owns equity in the company, and certain rights in the dendritic cell vaccine technology and corresponding intellectual property have been exclusively licensed by Cedars-Sinai to ImmunoCellular Therapeutics, including rights associated with ICT-107, the vaccine investigated in this clinical study.
Several members of the research and presentation team have ties to the company. Abstract co-author Keith Black, MD, a Cedars-Sinai physician, owns stock in the company. Senior author John Yu, MD, a Cedars-Sinai physician, owns stock in the company and is its founder, chief scientific officer and chair of the board of directors. James Bender, PhD, MPH, a co-author, is Immunocellular Therapeutics' vice president for product development and manufacturing. Elma Hawkins, a co-author, also is identified with Immunocellular.
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RESEARCHER RECEIVES $225,000 GRANT TO STUDY EPIGENETIC CHANGES ASSOCIATED WITH CHEMOTHERAPY
Western University cancer researcher Shun-Cheng (Shawn) Li, PhD, has been awarded a China-Canada Joint Health Research Initiative grant from the Canadian Institutes of Health Research (CIHR). The grant, valued at $225,000 over three years, is for a project titled "Systematic identification of dynamic epigenetic modifications in DNA damage repair for novel cancer therapy." Li is a professor in the Departments of Biochemistry, Oncology and Paediatrics at Western's Schulich School of Medicine & Dentistry.
These grants are jointly funded by the CIHR and the National Natural Science Foundation of China (NSFC) to promote Canadian-Chinese scientific co-operation. Fifteen projects are being funded in this round.
"This new grant will really allow us to map the landscape of the epigenetic changes associated with chemotherapy," says Li. "This is a new area in cancer research. We know the epigenetic changes, in addition to the genetic changes, are accounting for cancer and also play a role in drug response in chemotherapy. This work will identify novel targets for more effective cancer treatment."
Li welcomes the collaboration with the Chinese saying, "This will take advantage of the strengths in both labs. Cancer is a very complex disease; we're looking at how cancer is regulated at the epigenetic level. The scope of the project is pretty large and requires a multidisciplinary approach, so combining our skills and expertise will move this project forward much quicker than any lab could do on its own."
The announcement is just the latest recognition for the scientist. The Canadian Cancer Society named Li's research as one of "Canada's top 10 Cancer Research Stories of 2013" at the recent Canadian Cancer Research Conference. He also received a $200,000 Innovation Grant from the Canadian Cancer Society last month to find ways to overcome chemotherapy resistance in women with triple-negative breast cancer. In total, the Canadian Cancer Society has given Li's research $2.1 million since 2001.
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FDA APPROVES FIRST DRUG IN 4 DECADES FOR ADVANCED THYROID CANCER
The US Food and Drug Administration (FDA) has approved sorafenib (Nexavar), an oral kinase inhibitor, for metastatic, differentiated THYROID CANCER (the most common type). It is the first agent to be approved for this form of thyroid cancer in 4 decades.
Sorafenib is indicated for patients with either locally recurrent or metastatic, progressive differentiated thyroid cancer that no longer responds to radioactive iodine treatment, the first-line therapy for thyroid cancer. The drug was approved based on a priority review by the FDA and received an orphan drug designation.
³Differentiated thyroid cancer can be challenging to treat, especially when unresponsive to conventional therapies,² said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA¹s Center for Drug Evaluation and Research, in a press release. ³Today¹s approval demonstrates the FDA¹s commitment to expediting the availability of treatment options for patients with difficult-to-treat diseases.²
According to the National Cancer Institute, about 60,220 people in the United States will be diagnosed with thyroid cancer in 2013, and approximately 1,850 will die of the disease.
The approval of sorafenib is based on the 417-patient DECISION phase III clinical trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in June 2013. Sorafenib increased progression-free survival by 41% compared with placebo. Patients in the sorafenib arm had a median progression-free survival of 10.8 months compared with 5.8 months on the placebo arm (P < .0001).
Ninety-six percent of patients on the trial had metastatic differentiated thyroid cancer that had progressed within the prior 14 months following treatment with radioactive iodine.
In the trial, the most common adverse events in sorafenib-treated patients were fatigue, infection, diarrhea, alopecia, rash, hand-foot skin reaction, nausea, weight loss, decreased appetite, abdominal and gastrointestinal pains, and hypertension.
Patients may need adjustment of their thyroid hormone replacement therapy as sorafenib is likely to increase levels of thyroid stimulating hormone in patients.
Sorafenib has been approved as a first-line treatment for ADVANCED RENAL CELL CARCINOMA since 2005 and as a first-line treatment of hepatocellular carcinoma since 2007.
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HERPES VIRUS IN COMBINATION WITH CHEMOTHERAPY DESTROYS CANCER CELLS*
Two recent studies have found a novel way to combat cancerous tumors and cells. Researchers found that CHEMOTHERAPY when combined with herpes virus has the potential to kill enough tumors and cancer cells. The researchers said that if the right combination of herpes and cancer drugs is injected into the body, it could trigger the immune response to kill cancer.
Sam Workenhe, a postdoctoral researcher and project lead, said that this approach can directly target tumor cells and activate the immune system. "Cancer cells are constantly evolving to outsmart the body's immune response," Workenhe said. "Effective cancer therapies target tumour cells directly and initiate an 'anti-tumour' immune response that targets tumour cells, even in the absence of the original therapeutic agent."
During the initial testing, the researchers genetically engineered Herpes Simplex Viruses (HSVs) in a way that it replicates inside the body and eventually kills only the cancereous cells. When the modified version of herpes is injected into a tumor, it activates the body's natural immune response to fight the virus. When the virus has killed enough tumor cells, the body starts to identify the tumor and joins the fight as well.
"In our first study, we used HSV-1 and HSV-2 oncolytic viruses to activate the immune response, and in a parallel study we combined this with chemotherapy and noticed it induced tumour regression," Workenhe said.
Karen Mossman, the chairperson of McMaster's Department of Biochemistry and Biomedical Sciences said that in combination with chemotherapy, this approach could be tremendously effective. Plus, the immune systems are expert at killing viruses, which destroys the herpes quickly.
"The beauty of that is even once the virus is long gone, the immune system is now also recognizing those tumour cells, and so the immune system can continue to clear those tumours," Mossman said.
Mossman said that with the virus shows signs of killing the tumor, lower levels of chemotherapy can be used to provide a less toxic environment for the patient. This unique treatment has few side-effects. The patient might feel like he/she is suffering from a viral infection for a couple of days.
The experiment is currently in the last stages of trials on mice. The findings were published in the scientific journals Molecular Therapy and Cancer Immunology Research.
* It's my understanding that the herpes virus lives at the base of the spine. Outbreaks can be controlled, but never completely stopped because the virus can't be killed. This makes me wonder if a better outcome to chemotherapy is already being employed by the body in those of us with the herpes virus...and wouldn't that be a pleasant surprise!
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Have a safe and happy holiday season. See you next year! And please take a look at that drug discount program attachment, it will affect us all.
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And if you have any thoughts of how this newsletter could be improved, please email me directly, at Elaine@elainejesmer.com.