Thursday, December 25, 2008

Finding Chemo: Scanning the Sea Floor for New Drugs

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Permanent Link: Finding Chemo: Scanning the Sea Floor for New Drugs

The Centers for Disease Control and Prevention (CDC) has recently released a report detailing the numbers of deaths and years of productivity lost among people who died before 65 years-old because of asbestosis. The CDC’s report only looked at asbestosis-related deaths, so these numbers do not take into account deaths from any of the forms of malignant mesothelioma, such as pleural mesothelioma or peritoneal mesothelioma, or from asbestos-induced lung cancer. Even without including these other diseases, however, these numbers speak to the devastating effects that decades worth of asbestos use have had on human health.

To create this report, the CDC looked at all examples of asbestosis-related deaths between 1968 and 2005, which totaled 9,024. From within this figure, they identified 1,169 individuals who died between the ages of 25 and 64. 65 years-old is the common cutoff used to differentiate a hypothetical worker’s most productive years from his or her less productive ones, so asbestos-related deaths among people 65 and over were dropped from this study. Among the 1,169 cases identified, the CDC then developed a scale of “annual years of potential life lost before age 65”, which has been abbreviated to YPLL. This figure is the difference between a person’s age at time of death and 65, so a person who died at 55 had would have a YPLL of 10. The CDC looked at trends within these cases in 5-year periods and they also counted the total YPLL for the entire study period.

As we said above, there were 1169 individuals who died from asbestosis before they were 65. Total years of potential life lost were 7267 YPLL, with a mean YPLL for each person who died of 6.2 years. The CDC also reports that YPLL is increasing over time—even though asbestos use has been heavily regulated since the 1970s. For the first five years under steady (1968-1975), YPLL was 146.0. For the last five years however (2001-2005), YPLL was 239.6: an increase of 64%. While the available data on industry and occupation were a small subset of the total study population statistics, the study also showed that construction, ship building and repair, and military were the hardest hit industries, while insulation workers, and then administrations, plumbers and pipe and steamfitters were the hardest hit occupations.

This study is a further example of the tragedy of asbestos-related diseases in the United States and around the world. Even though regulations regarding the handling of asbestos have been in place for decades now, it’s clear from this study that more and more people are dying from asbestosis.

Labels: asbestos, mesothelioma

UK paper The Telegraph is a running a story on a woman named Debbie Brewer, who was diagnosed with pleural mesothelioma in November of 2006 and is being treated with a form of chemotherapy called chemoembolisation, which features a direct application of chemotherapy agents into the malignant areas. Whereas traditional chemotherapy is a systemic treatment where the drugs are injected into the blood stream and circulate throughout the body, with chemoembolisation, the drugs are delivered to the actual tumor cells through a catheter.

Chemoembolisation is more often used for cancers that feature individual tumors with distinct boundaries, as opposed to mesothelioma which is most often characterized by a diffuse spread of malignant cells throughout a surface area. However, for Debbie Brewer, the treatment has been totally effective: the oncologists at the University Clinic in Frankfurt, Germany, the center where she has been treated, have declared her in remission. Because of the success in treating her disease, Debbie is spending Christmas with her family.

Original Title: “Pioneering treatment enables cancer sufferer to spend Christmas with family”

Labels: chemotherapy, mesothelioma, pleuralmesothelioma, treatments

Difficulties in the long term management of malignant mesothelioma are one of the most common topics covered on this site. Even as recent years have seen improvements in our ability to treat patients with pleural mesothelioma and peritoneal mesothelioma, the disease remains without a cure and median survival times are still much too short. This situation has spurred physicians and researchers throughout the world to investigate novel therapeutic options using a number of different agents and modalities. Some of these studies have identified possibly new avenues of treatment, while others have confirmed a similar lack of efficacy as to the standard therapies. In all cases, however, research into creating more effective mesothelioma treatment options continues all over the world.

A paper describing the results of a new chemotherapy regimen was recently published in the Journal of Occupational Medicine and Toxicology. The study under discussion was conducted by researchers from Germany who were investigating the efficacy of chemotherapy involving oxaliplatin monotherapy or oxaliplatin in combination with gemcitabine in patients with pleural mesothelioma who had previously been treated with pemetrexed and a platinum agent.

The study enrolled 29 patients between February 2005 and September 2007 and analyzed their performance along a number of axes, including: response rate, disease control rate, overall survival, time to progression, progression-free survival, time to treatment failure and toxicity.

The authors report survival median survival from the start of treatment at just over 24 weeks (24.3), with overall survival for the patients from original diagnosis at almost 72 weeks (71.7). They also report median time to progression at 9.3 weeks. The article reports that 13 of 29 patients experienced a partial response or stable disease, for a disease control rate of 44.8%, while 55.2% of patients (16 of 29) experienced progressive disease. Toxicity was well managed, with no Grade 4 toxicities noted in the patient cohort.

With a disease control rate of nearly 45% and no grade high level toxicities reported, the authors conclude that until more data on alternative treatments is available oxaliplatin in combination with gemcitabine should be considered an option for patients with relapsed pleural mesothelioma.

Labels: chemotherapy, mesothelioma, pleuralmesothelioma, treatments

Scientists from Ohio State University have announced exciting results from a study they were conducting on the manner in which asbestos fibers interact with human cells and, possibly, cause mesothelioma. For the first time in the history of asbestos science, the scientists have identified a particular mechanism by which crocidolite fibers bind to the cell surface of human cells. The scientists are hopeful that an understanding of the molecular biology of fiber and cell interaction will lead to the development of more effective treatments for pleural mesothelioma and peritoneal mesothelioma, as well as asbestos-induced lung cancer.

The findings are still quite preliminary and the scientists caution that any therapeutic development is years ago, but these results are still important as an identification of part of the carcinogenic pathway that leads from asbestos exposure to malignant mesothelioma. Some asbestos fibers are thought to dissolve when exposure occurs, but most do not break down over time, so the identification of the binding mechanism can focus scientists on the particular signaling cascade that occurs after the fiber binds to the cell. An understanding of this cascade could possibly let scientists develop treatments to arrest the growth of the mesothelioma, or possibly, give scientists a target to develop therapies that will prevent mesothelioma’s development in the first place.

The scientists were only studying the crocidolite asbestos, which is also known as blue asbestos, but they hope to expand their study to include the give other common forms of the mineral. Crocidolite is considered among the most carcinogenic forms of asbestos.

Labels: asbestos, mesothelioma

We have written a number of recent articles about the impact that nanotechnology is having on cancer treatments and this article continues that recent focus. A multidisciplinary team of scientists and oncologists at the University of California at San Diego have developed a nanoparticle, what they are calling a “smart bomb,” that effectively targets the distant spread of tumor cells by increasing the efficacy by which chemotherapy can de delivered to them. Working on a study involving pancreatic cancer and kidney cancer, the researchers were able to develop a delivery system for the chemo agent doxorubicin that targeted tumors cells that had metastasized to other parts of the body. Metastasis is always a difficult treatment situation and is often the manner by which cancers kill a patient, so developing methods of containing and/or combating it is one of the most pressing topics in contemporary cancer research.

The researchers describe the technology as targeting specific protein markers on the surfaces of metastatic lesions. These tumors are highly dependent on the development of new blood vessels, a process which offers distinct targets for the nanoparticle to bind with and deliver the chemotherapy to. The researchers report that the therapy inhibited the metastatic spread of the cancers in most of the mice under study.

Another benefit to this technology was its much better tolerability than traditional doxorubicin-based treatments of metastatic pancreatic and kidney cancers. Because the delivery mechanism is able to target tumor cells more efficiently, the total dosage level of the doxorubicin can be reduced, even as a higher percentage of the agent is delivered to the malignancy. The researchers report that while previous trials involving doxorubicin often demonstrated significant toxicity among the patients under study, the mice in their tests did not display the same levels of weight loss and system toxicity as is normally seen.

Nanotechnology is truly revolutionizing cancer treatments, but much more work is needed before these research questions are approved for human-based trials and treatments. Hopefully, the day for these trials and treatments is coming soon. With aggressive diseases such as pleural mesothelioma and peritoneal mesothelioma, these new technologies are offing hope for patients and doctors alike.

Labels: cancer, chemotherapy, treatments

Labels: cancer, chemotherapy, treatments

The hypothesis that most forms of tumor genesis are driven by cancer stem cells has been one of the most exciting ideas in oncology research for a number of years now. The basic theory is that a small number of cells (co-called stem cells) are the principal catalysts for tumor development and treating these specific cells is a more effective method for stopping the growth of cancer than treating the entire tumor. However, the results of a recent study—conducted by an oncologist who has championed the stem cell theory—have cast serious doubt on the viability of this concept for many common cancers.

Sean Morrison, director of the Center for Stem Cell Biology at the University of Michgan’s Life Sciences Institute and the principal founder of Oncomed, a biotech startup focused on cancer stem cell treatments, was studying the growth of melanoma cells in mice and discovered that upwards of 25% of these tumors’ cells were fully tumorgenic—a much higher figure than the stem cell theory predicts. He was quick to note that these findings do not entirely invalidate the model, but they are indicative that many forms of cancer, such as melanoma and solid tumor cancers, do not conform to the stem cell model and treatments that are based on this model will likely be less effective—or not effective at all—for these types of cancers. Mr. Morrison is a highly-regarded oncologist who has long been associated with the stem cell theory, so for him to come to the conclusion that the theory may not be as wide-ranging as hoped is an important development for people who are following the research on this topic.

One of the leading critics of the theory, Steve Kern from John Hopkins, was not surprised by the findings and thinks they are indicative of many of the problems that he, and other critics, have previously noted. However, both Mr. Kern and Mr. Morrison believe that the stem theory may still be applicable for other forms of cancer, such as leukemia, which has a very different oncogenic pattern than carcinomas, sarcomas and other solid tumors. More information about the treatment efficacy of this theory will come out when the clinical trial that is studying Oncomed's leading drug, OMP-21M18, is completed.

Advances in cancer research during the last ten years have defininitely had positive effects on our ability to diagnose and to treat cancer, and we have all benefited from these advances. Even as the results of this study indicate that no panacea is likely to be found for cancer treatments, the dedication and creativity of our greatest cancer researchers gives us all hope that treatments for seemingly intractable cancers, such as pleural mesothelioma and peritoneal mesothelioma, will be developed in the future.

Labels: cancer, treatments

Labels: cancer, chemotherapy