 |
 |
|
||||||||||||||||
|
|
|||||||||||||||||
|
Activating Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor Are Associated with Improved Survival in Gefitinib Treated Chemorefractory Lung Adenocarcinomas-(Clin Cancer Res-15/08/2005) Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) confer a strong sensitivity to gefitinib, a selective tyrosine kinase inhibitor of EGFR. :EGFR mutations were examined at exons 18, 19, and 21 in tumor tissue from 68 gefitinib-treated, chemorefractory, advanced non-small cell lung cancer patients from the United States, Europe, and Asia and in a highly gefitinib-sensitive non-small cell lung cancer cell line and correlated their presence with response and survival. In addition, in a subgroup of 28 patients for whom the remaining tumor tissue was available, we examined the relationship among EGFR mutations, CA repeats in intron 1 of EGFR, EGFR and caveolin 1 mRNA levels and increased EGFR gene copy numbers. Seventeen patients had EGFR mutations, all of which were in lung adenocarcinomas. Radiographic response was observed in 6 of 7 (94.1%) patients harboring EGFR mutations, in contrast with 6 of 51 (2.6%) with wild-type EGFR (P< 0.0001). Probability of response increased significantly in never smokers, patients receiving a greater number of prior chemotherapy regimens, Asians, and younger patients. Median survival was not reached for patients with EGFR mutations and was 9.9 months for those with wild-type EGFR (P=0.001). EGFR mutations tended to be associated with increased numbers of CA repeats and increased EGFR gene copy numbers but not with EGFR and caveolin-1 mRNA overexpression (P=not significant). It was concluded that the presence of EGFR mutations is a major determinant of gefitinib response, and targeting EGFR should be considered in preference to chemotherapy as first-line treatment in lung adenocarcinomas that have demonstrable EGFR mutations. Lung Cancer Deaths Declining for Europe's Men-(HealthDayNews-22/07/2005) Lung cancer deaths for men are falling in most European Union countries, including all new member states from central and eastern Europe, according to a study in this week's issue of the British Medical Journal. Only four countries -- Portugal, Greece, Spain and France -- showed no evidence of a decline in the male death rate across the 35-to-54 age range, the point in the lifespan when up to 90 percent of cases are caused by smoking. However, increasing numbers of European women are dying from lung cancer, the study found. The greatest increases were in France, Spain and Hungary, with rates for women in Hungary exceeding those for women in all other member states. Researchers suggested that changes in cigarette manufacturing may have contributed to the decline in lung cancer among young men. In Poland, for example, tar yields fell by more than half between 1984 and 1999. Researchers reported this week that doctors can now add a potent weapon, combining surgery and chemotherapy, to their arsenal in the fight against lung cancer. The study comes at a time when new treatments for other forms of cancer have made the disease manageable for many, while the statistics on lung cancer have remained stubbornly grim. Almost three fourths of people diagnosed with lung cancer die within two years, and at the five-year mark, only 15 percent are still alive. For those with non-small-cell lung cancer, the most common kind, the best odds of survival have come by surgically removing as much of the cancer as possible, then hoping for the best. But U.S. and Canadian researchers have found that giving patients chemotherapy after surgery increases five-year survival to 69 percent from 54 percent with surgery alone, according to a study published in the New England Journal of Medicine. That is a big increase, since in cancer treatment, incremental progress is the norm. Indeed, on the basis of those data, wrote Katherine Pisters, an oncologist with the M.D. Anderson Cancer Center in Houston, in an editorial accompanying the study, "the controversy surrounding adjuvant chemotherapy for [surgically removable] non-small-cell lung cancer is over." (Earlier studies of older forms of chemotherapy showed little benefit or even some harm from side effects, causing debate over whether it should ever be used, but newer drugs are more effective.) The biggest caveat is that the success of the treatment depends on catching the cancer at its early stages, when it can still be surgically removed. That is tough, since there is no equivalent of screening tests like mammograms to find lung cancer. About 50,000 of the more than 170,000 people diagnosed with lung cancer this year in the United States will find their disease early. But for those people with early-stage non-small-cell lung cancer, the change in treatment will likely begin immediately, based on the strong evidence and the fact that there is no new drug approval needed—the chemotherapy used in the study consisted of two drugs, cisplatin and vinorelbine, that are already being used to treat other cancers. There's likely to be further research to figure out exactly which patients will be most helped by the chemotherapy, how to cut down on unpleasant side effects, and whether this is the best combination of drugs to use. New Lung Cancer Surgery Speeds Healing-(HealthDay News-06/06/2005) A new minimally invasive surgery called thoracoscopic lobectomy can reduce pain and recovery time for patients with early stage lung cancer, according to a Michigan surgeon who is one of the first in the country to use the technique. The procedure involves the removal of a portion of the lungs without spreading open the ribs or cutting large muscles, which occurs in traditional lung cancer surgery. With this new technique, the surgeon makes three small incisions and then inserts a miniature camera through a fourth incision. This 'keyhole' approach allows the surgeon to view the inside of the chest during the operation. According to Dr. Allan Pickens, a thoracic surgeon at the University of Michigan Comprehensive Cancer Center, in Ann Arbor, thoracoscopic lobectomy allows patients to leave the hospital in half the time of conventional lung cancer surgery. Many return to work within two weeks, he said. "It's a way of treating cancer with a less invasive procedure that will get patients back to their regular activities sooner," Pickens said in a prepared statement. Lung cancer cases double in 30 years: Cancer Research UK-(Yahoo News-10/05/2005) Worldwide cases of lung cancer have doubled in the past 30 years, to more than 1.4 million cases diagnosed in 2002, according to research from Cancer Research UK. In contrast, the British research group said in a report there were 600,000 diagnoses made for the cancer -- one of the most lethal forms, with a survival rate of less than one in seven cases -- in 1975. The number of all cases of cancer was also on the rise as the global population ages, with 10.9 million cases diagnosed in 2002 and 6.7 million deaths, it said. In Britain, while the cancer diagnosis rate was up, the death rate was actually falling, it added. "Thanks to research, many more people diagnosed with cancer in 2005 will survive compared to 1975," the organization's medical director John Toy was quoted as saying. FDA Limits Use of Lung Cancer Drug Iressa-(Yahoo News-21/06/2005) People newly diagnosed with lung cancer should not take the lung cancer drug Iressa, according to new limitations placed on the drug by the FDA. Following results of a large study that showed Iressa did not help people with the disease live longer, the FDA says only lung cancer patients already using Iressa whose doctors believe it is helping them should continue to use the drug. New lung cancer patients will only be able to use Iressa as part of strictly controlled clinical trials. Iressa was approved for treating lung cancer in May 2003 under a special FDA program that allows drugs that appear promising to be approved despite absolute proof that they increase survival. Initial studies of Iressa showed that 10 percent of people with lung cancer responded to the drug in terms of slower tumor growth after other available treatments failed. But two studies that were published after Iressa’s approval have shown that the drug didn’t live up to its expectations, and people taking the drug did not live any longer than those taking a placebo. Officials say that since 2003, other drugs, such as Tarceva, have been approved and shown to prolong the lives of difficult-to-treat lung cancer patients. The FDA says it is not considering taking Iressa off the market, and the results of new and ongoing studies of the drug will determine its role in lung cancer treatment. Can Chest X-Rays Find Lung Cancer Early?-(Yahoo News-25/04/2005) When the news that Peter Jennings had lung cancer was reported, many asked why doctors don't use chest X-rays to diagnose lung cancer at an early stage, when it's more treatable. Cancer expert Harold Burstein, MD, assistant professor of medicine at Harvard Medical School in Boston, provided the answer. "Lung cancer is the No. 1 cause of cancer death in the U.S. for both men and women. The vast majority of lung cancer cases are caused by smoking," said Burstein. "Thus, lung cancer simultaneously represents the most devastating cancer in our society, and the most preventable." He says there are good screening tests for many types of cancer, such as Pap smear for cervical cancer, mammogram for breast cancer, and colonoscopy for colorectal cancer. But what about chest X-rays for lung cancer? "The answer is surprisingly complex," he says. Chest X-rays are inadequate for diagnosing lung cancers at an early stage, when they are more treatable. "By the time lung cancers are discovered on chest X-ray, the tumor is often too far advanced to allow the patient to be cured with surgery or radiation therapy. Chest X-rays often miss small, potentially curable lung tumors, as they are too hard to see," says Burstein. In addition, many things seen on a chest X-ray turn out to be benign problems. "If you start getting lots of screening chest X-rays, you end up performing other testing on many patients, which are often unnecessary." In recent years, a lot of attention has been paid to high-tech scans called high resolution, spiral CT scans. The hope was that these CT scans would be able to find smaller, earlier cancers without leading to further unnecessary tests. "A variety of recent studies in the U.S. and Japan have suggested that high-resolution CT scans can often detect lung cancers. In particular, these cancers seem to be small (stage I), suggesting that they may be more likely to be cured with surgery," says Burstein. However, he explains that these were small, early studies that were not able to answer the questions of whether CT scans can actually save lives. Burstein says that a recent analysis of potential lung cancer screening tests shows there is inadequate data to recommend widespread lung cancer screening at this time. The report by the federal Agency for Healthcare Research and Quality and the U.S. Preventive Health Services Task Force says evidence that chest X-rays, CT scans, and other forms of screening can save lives is poor. "In the case of lung cancer, prevention remains the best cure. If you care about someone, try to get them to stop smoking," Burstein says. Procedure Improves Outcomes in Lung Cancer Cases-(HealthDay News-25/01/2005) A combination of intraoperative brachytherapy with sublobar surgical resection improves outcomes for high-risk lung cancer patients, says a new study by researchers at Allegheny General Hospital in Pittsburgh. Intraoperative brachytherapy involves inserting tiny pellets that contain radioactive medication into an area of the lung from which a tumor has been surgically removed. Sublobar resection is a procedure in which only a small part of the lung is removed. This study of 167 patients with stage 1b non-small cell lung cancer found that combining these two treatments reduced local cancer recurrence and improved patients' clinical outcomes.The study was presented at the Society of Thoracic Surgeons annual meeting in Tampa, Fla. "In most cases, early non-small cell lung cancer can be treated successfully with surgery if the cancer has not spread beyond the chest. Unfortunately, some patients with this disease are poor candidates for the ideal surgical intervention, lobectomy, due to poor pulmonary health or other medical issues," principal investigator Dr. Robert Keenan, director of the division of thoracic surgery, said in a prepared statement. Lobectomy is the most common form of lung cancer surgery. It involves removal of an entire lobe of one lung. "Though sublobar resection alone is associated with an increased incidence of post-operative disease recurrence, it is still advocated for high-risk patients in the absence of a good alternative. Our study suggests that adding brachytherapy to the regimen can make a dramatic difference in outcomes," Keenan said. New procedure will improve detection of lung cancer-(Yahoo News-25/08/2004) With the addition of a new procedure that can detect cancer in the lung incredibly early, Southwest Regional Medical Center is hoping to continue making a push to become a premier medical facility in central Arkansas. A fluorescent bronchoscope is a device that will be available at Southwest in September, and patients already are making appointments. Southwest will have the only one in Arkansas and only the second one in a non-teaching facility in the United States. Dr. Chris John of Southwest Pulmonary Associates is overseeing the use of the device, and he is excited about the possibilities it can provide for the people in the area. "Our hope is that we will be able to find those at risk of lung cancer at a much earlier stage," John said. "When most people are diagnosed with the use of a chest X-ray or other device, it is usually much too late to keep the cancer from spreading. With this bronchoscope, areas that would have never been detected before will be found, and treatment can begin much earlier." John said that some cancerous tissue in the lungs are invisible to other devices, especially in the early stages. What the fluorescent bronchoscope does is provide a type of "night vision" into finding metaplasia and dysplasia in people at risk. The scope goes through the body's main airways and shines a fluorescent blue filter into certain tissue areas. Over healthy tissue, the light will bounce back in a greenish color, but over abnormal tissue, green is not allowed to bounce back, and what is left is a reddish, brownish color. What was invisible to other procedures will be routine with the new device. With those early detections, John said, doctors will be able to go in and destroy the cancerous tissue before they ever cause a serious problem. John said he believes it is especially important in Arkansas, where the number of smokers is very high. John said lung cancer is the most common killer of adults because of the malignancy of many diagnoses. The new procedure will be able to pick up 70 percent more cancer than more traditional methods. John was responsible in bringing the bronchoscope to Southwest after seeing it and learning about it at several medical meetings. The procedure has not been used on a widespread basis in the United States, but it has been used successfully in Europe. Only 114 are in use around the world, but John said he believes that the success of the bronchoscope will eventually make it a common procedure. Southwest will begin using the bronchoscope Sept. 10, and John said he is hoping that anyone "at risk" will schedule an appointment. These would include individuals who smoke 20 packs a week and anyone exposed to asbestos. Because it is an evaluation procedure and because it is very rare in the United States, John is unsure about the how one's medical insurance would be involved, but he noted that over the long term, early detection could save a person around $30,000. "It is an outpatient procedure, and it usually takes about 20 minutes," he said. "It could be considered the same as an exercise test that is given to certain patients, and eventually it will be recognized as a screening and preventative procedure." Anyone who is interested in the procedure may contact John at 407-0200. F.D.A. Approves a Pill for Lung Cancer to Be Sold by Genentech and OSI-(Yahoo News-19/11/2004)
The drug is expected to compete most directly with AstraZeneca's Iressa, a similar drug that was approved in 2003. Tarceva's advantage is that in a clinical trial it was shown to prolong lives, by a median of 6.7 months compared to 4.7 months for patients who got a placebo. So far, Iressa has only been shown to shrink tumors. Both drugs, as well as ImClone Systems' colon cancer drug, Erbitux, try to block a particular protein, the epidermal growth factor receptor, that spurs the growth of cancer cells. Such so-called targeted drugs tend to have fewer side effects than conventional chemotherapy. The main side effects of Tarceva are a rash and diarrhea, although there have been infrequent reports of serious or even fatal lung disease in patients taking the drug. Tarceva might also compete with Alimta from Eli Lilly and Taxotere from Aventis, both approved second treatments for lung cancer. Tarceva, a pill taken once a day, will be priced at slightly more than $2,000 wholesale for a month's supply, said Colin Goddard, chief executive of OSI. Patients and doctors have complained recently about the high prices of cancer drugs. Dr. Goddard defended the price of Tarceva, saying it was "set competitively against the other drugs in play." He said the drug was priced at a few hundred dollars more per month than Iressa but less than many other cancer drugs. In another clinical trial, Tarceva was found to extend the lives of patients with pancreatic cancer, which is extremely difficult to treat. The companies plan to apply for approval for that use next year, Dr. Goddard said. Tarceva did not work when tested in combination with chemotherapy as an initial treatment for lung cancer. That would have been a bigger potential market than treatment of patients who fail to respond to chemotherapy. Vivant Medical, Inc. and Rhode Island Hospital Announce Beginning of Clinical Study in Microwave Ablation for the Treatment of Lung Cancer-(PRNewswire-20/09/2004) Vivant Medical and Rhode Island Hospital announced the beginning of a clinicalstudy to determine the effectiveness of microwave ablation for treatment of lung cancer. In the study, Rhode Island Hospital will be using Vivant's VivaWave(TM) Ablation System, which has received FDA 510(k) clearance for coagulation of soft tissue. Damian Dupuy, MD, Director of Minimally Invasive Therapy and Ultrasound at Rhode Island Hospital, will be the principal investigator. Microwave ablation is a new, heat-based treatment used to destroy tumors. Under the lead of Dr. Dupuy, Rhode Island Hospital's staff has already performed procedures in over 50 patients using VivaWave to ablate multiple masses in soft tissues including kidney, liver, bone, and adrenal glands. Due to its consistency, predictability, safety, reduced procedure times, and ability to treat large lesions, the VivaWave system is being developed as a promising and attractive option for patients with lung cancer who are typically not candidates for surgery and may not be able to be treated with current thermal therapy such as radio-frequency ablation. To date, Rhode Island Hospital is the largest user of microwave ablation. Dr. Dupuy, said, "This development is in keeping with Rhode Island Hospital's commitment to providing our patients with the most recent advances in cancer treatment. Our research will result in a greater understanding of cancer and more effective, less traumatic treatment for our patients." Dupuy also noted, "As a large majority of lung cancer patients are not surgical candidates, VivaWave and microwave ablation offers doctors and their patients a much-needed option." "We are pleased with the initiation of this study and look forward to broadening the use of the VivaWave system for the treatment of lung cancer," said Rod Young, Chief Executive Officer at Vivant Medical. "Approximately 174,000 new cases of lung cancer will be diagnosed in 2004, accounting for 13% of all new cancer cases. We believe that the VivaWave has the potential to aid doctors in effectively and safely treating patients with lung cancer who are left with precious few alternatives." Dr. Dupuy was one of the pioneers in the development of radio-frequency ablation, the current industry standard in thermal ablation. Attracted by VivaWave's potential versus radio-frequency ablation, Dr. Dupuy is now a leading expert in microwave ablation. Data Confirm 30% 1-YEAR Survival For Gefitinib In Non-Small Cell Lung Cancer-(Yahoo News-08/09/2004) Final survival data from more than 21,000 non-small cell lung cancer (NSCLC) patients who received gefitinib through AstraZeneca's compassionate use programme (also known as an Expanded Access Programme, EAP) were presented at the European Respiratory Society (ERS) Congress. The one-year survival rate in patients treated with gefitinib on a compassionate basis was reported as 29.9%. Historical data show that patients treated with third- or fourth-line chemotherapy have a one-year survival rate of just 5.5%. This EAP data set represents the largest reporting to date of clinical use of an epidermal growth factor receptor (EGFR) agent. Gefitinib, the most extensively prescribed EGFR agent, has been administered to over 178,000 patients worldwide to date. In 2000, more than 375,000 people were diagnosed with lung cancer and over 345,000 people died from the disease in Europe. Data were presented from 21,064 patients treated with gefitinib. Patients were eligible for treatment who had stage III/IV NSCLC, who had received and failed prior chemotherapy or radiation therapy, or were unable to tolerate chemotherapy. Results showed: 1-year
survival was 29.9% (95% CI, 28.8 - 31.1) Judith Ochs M.D., Senior Director Clinical Research, lead author of the study at AstraZeneca commented: "The results reported in the phase II IDEAL studies showed that ~30% of patients were alive one year after starting treatment, and the results presented today from this large population of patients further support these findings. The IDEAL trials also demonstrated that ~50% of patients gain clinical benefit from treatment with gefitinib and these EAP data give us a valuable insight into what is likely to happen with gefitinib in a typical clinical population with advanced NSCLC." The gefitinib Expanded Access Programme (EAP) was initiated in 2000 to allow those patients with advanced NSCLC and no other treatment options access to the drug before registration. The US programme ran from August 2000 to July 2003 and enrolled over 23,300 advanced (stage III/IV) NSCLC patients who had exhausted all approved treatment options or were unable to tolerate chemotherapy. Lung cancer is the leading cancer killer in the world, causing more deaths each year than breast, prostate and bowel cancer combined. In 2000 there were over 1.2 million people diagnosed with lung cancer worldwide and more than 1 million people died from the disease. NSCLC is the most common form of lung cancer, accounting for 80 percent of all lung cancer cases. Gefitinib has been approved for the treatment of advanced NSCLC in 29 countries, including the US, Japan, Canada, Switzerland and Australia, and is currently undergoing review with many other regulatory authorities worldwide Lung Cancer Different in Nonsmokers-(Reuters Health-18/08/2004) Among individuals who develop lung cancer, there appear to be differences between smokers and nonsmokers in survival rates and in individuals patient characteristics, researchers report. They say the findings indicate that lung cancer in nonsmokers is a specific disease, which has implications for research and clinical trials. Dr. George R. Simon and colleagues from the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, analyzed patient characteristics and survival rates in 132 individuals who never smoked and in 522 current smokers diagnosed with primary lung cancer. They observed that never-smokers were generally older at diagnosis (63.5 years versus 59.4 years) and more often female (78 percent versus 54 percent). Also, never-smokers had better overall survival rates than current smokers, with survival estimates at 5 years of 23 percent versus 16 percent. After adjusting for other risk factors, smoking was an "independent negative prognostic factor," the investigators report in the medical journal Chest. Commenting on these findings, Simon told Reuters Health that lung cancer in smokers is the result of the "carcinogenic properties of chronic tobacco use." In contrast, lung cancer in never-smokers occurs without exposure to the carcinogenic properties of tobacco. Therefore, lung cancer in nonsmokers has a distinct behavior and survival rate. Lung cancer in never-smokers "is a different disease in itself, with its own unique biology, behavior characteristics, and survival," Simon concluded. "Therefore, we assert that laboratory and clinical investigations be specifically designed to further study this distinct disease entity." Dr. Peter J. Mazzone and two colleagues from The Cleveland Clinic Foundation in Ohio concur, noting in an editorial in Chest that this study "further highlights the importance of stratification of patients for smoking history in future clinical trials." Avastin-Tarceva Combo Provides 'One-Two Punch' Against Top Cancer Killer-(AScribe Newswire-28/06/2004) Results of the first clinical trial to combine two new targeted cancer drugs suggest that the combination may provide a powerful "one-two punch" against lung cancer, the nation's leading cancer killer. The work, led by researchers at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., and The University of Texas M.D. Anderson Cancer Center in Houston, was presented at the 40th annual meeting of the American Society of Clinical Oncology. Tumors were controlled among 85 percent of the 40 patients with advanced non-small cell lung cancer (NSCLC) who entered the Phase I/II trial of a combined regimen of bevacizumab (Avastin TM) and erlotinib (Tarceva TM).The response rate - proportion of patients whose tumors shrank in size by more than half - was about 20 percent, while median survival was 12.5 months. This compares to about 10 percent response and between six and eight months median survival with traditional therapy or erlotinib alone, said Alan Sandler, M.D., associate professor of Medicine and director of the lung cancer clinical program at Vanderbilt-Ingram. The treatment resulted in only mild side effects, including rash and diarrhea, and the drugs did not appear to interact adversely with one another, the investigators report. "The anti-tumor activity was encouraging," said Sandler, who presented the research at the meeting. "These findings suggest not only that combining these two agents is feasible, but that this approach may provide a one-two punch against tumors that should be further examined in larger clinical trials." Lung cancer is the leading cause of cancer death in the United States, killing more than 157,000 people each year, more than the next four leading cancers (colorectal, breast, prostate and pancreas) combined. About 85 percent of all lung cancers are non-small cell cancers, and nearly half of these patients are diagnosed with advanced disease and receive only chemotherapy or supportive care, the investigators say. Despite newer third-generation chemotherapies, most of these patients become resistant to treatment or develop side effects so severe that they cannot continue treatment. "Less toxic and more effective treatments are clearly needed," Sandler said. The two drugs, both delivered orally, are among newer so-called targeted cancer agents that focus on specific molecular features of cancer cells. Because they potentially target cancer cells while sparing healthy cells, the hope for these new agents is more effective cancer therapy with fewer side effects. Bevacizumab blocks the vascular endothelial growth factor (VEGF), which is involved in making new blood vessels (a process called angiogenesis) that help feed tumor growth and spread. Erlotinib inhibits the epidermal growth factor receptor (EGFr), a key player in delivery of signals that prompt the runaway cell growth that characterizes cancers. Increased activity of the EGFr pathway, as well as increased number of tumor blood vessels resulting from VEGF expression, are associated with poorer outcomes for patients with NSCLC, the investigators note. Other research has suggested that activities of EGFr and VEGF are related - EGFr appears to play a role in angiogenesis, while blocking VEGF appears to interrupt EGFr signaling. As a result, the researchers suspect that a dual blockade of these targets may be synergistic. Interim results from this research were presented at last year's ASCO meeting in Chicago, prompting other investigators across the country to examine this combination in other tumor types as well as combine other targeted agents in clinical trials, Sandler said. At the time the study was launched, it was the first time two drugs that had not yet been approved by the U.S. Food and Drug Administration were combined in a trial. Since that time, bevacizumab has been approved for use in advanced colorectal cancer in combination with chemotherapy. Sponge substance works well with yew derivative to thwart cancer cell proliferation-(Yahoo News-15/06/2004) A drug derived from an ocean-growing sponge teams up to enhance the performance of the yew tree derivative Taxol® (paclitaxel) in preventing the growth of cancer cells, according to research published in the journal Cancer Research. Indeed, discodermolide, a novel drug isolated from the marine sponge Discodermia dissoluta, works with paclitaxel to thwart tumor cell growth--with several times the efficacy that either drug alone exerts on proliferating cancer cells. Studies by Mary Ann Jordan, Ph.D., a scientist at the University of California, Santa Barbara, and an international team of cancer researchers including postdoctoral fellows Stephane Honore, Ph.D., and Kathryn Kamath, Ph.D., demonstrate that the combination of the two drugs inhibited proliferation of human lung cancer cells by 41 percent. Administered alone, either discodermolide or paclitaxel prevented the cancer cell growth by only 9.6 or 16 percent, respectively. The drugs also combined to induce programmed cell death, or apoptosis, in the lung cancer cells. "Our results indicate that Taxol® and discodermolide have the potential to improve cancer patients' responses and reduce undesirable side effects when the two drugs are administered together," Jordan said. The drugs, which stem from naturally occurring sources, work in concert to stabilize the assembly/disassembly process of microtubules in cells. Microtubules--lengthy polymers made up of protein bundles, called tubulin--form long, straw-like cylinders that help shape the skeletal structure within cells and also move cellular components within the cell, including vesicles, granules, organelles like mitochondria, and chromosomes. Their attachment with chromosomes, the DNA genetic material in cells, is critical for cell replication and growth. Microtubules normally exist in a state of dynamic instability, where the polymers grow rapidly--longer or shorter, depending on the need of the cells. In this study, discodermolide and paclitaxel combined to alter the overall microtubule dynamics by 71 percent when administered together. Alone, they each reduced microtubule dynamic instability by 24 percent. By altering the stability dynamics of microtubules, paclitaxel and discodermolide limit cancer cells ability to duplicate DNA and divide. The cells are stuck in a pre-division stage of the cell cycle called G2/M. Cancer cells that are restricted to the pre-division stage of the cell cycle cannot divide and ultimately die, thus reducing proliferation of tumor cells. Both drugs work by binding to the microtubules. Because of their lengthy structure and the number of drug binding sites normally associated with them, microtubules are unique receptors for drugs within cells. Paclitaxel is currently an approved therapeutic for control of cancer growth. Discodermolide is currently under study in phase one clinical studies. Introgen's INGN 241 Combined With Radiation Increases Survival in Animals With Human Lung Cancer-(PR Newswire-28/06/04) Introgen Therapeutics, Inc. announced the publication of new preclinical data from studies evaluating INGN 241 in combination with radiation therapy in an animal model non-small cell lung cancer (NSCLC). INGN 241 currently is in Phase 2 clinical trials in malignant melanoma and has completed Phase 1 - 2 studies in multiple solid tumor indications. The paper, titled "Adenovirus- Mediated mda-7 (IL-24) Gene Therapy Suppresses Angiogenesis and Sensitizes NSCLC Xenograft Tumors to Radiation," reports data from studies conducted by researchers at The University of Texas M. D. Anderson Cancer Center in collaboration with Introgen scientists and is available in the current version of Molecular Therapy. "These data provide the first molecular basis for the inhibition of tumor growth by INGN 241 in combination in radiotherapy," said Sunil Chada, Ph.D., Introgen's director of Research and Development. "The formation of new vessels, a process known as angiogenesis, is essential for tumor growth. In the absence of angiogenesis, cells within the tumor are starved of oxygen and nutrients and die. The importance of angiogenesis in tumor growth has been validated by the recent approval of the first anti-angiogenic cancer therapy. In addition to its anti-angiogenic activity, a substantial body of data demonstrates that the MDA-7 protein has multiple anti-cancer effects, including inducing cell death, stimulating the immune system, reducing cell migration and metastasis and sensitizing cells to the effects of chemotherapy or radiation. Based on these activities, we believe that INGN 241 has enormous potential in treating a variety of cancers." The studies were conducted in the laboratory of Dr. Raymond E. Meyn, professor and chairman of the Department of Experimental Radiation Oncology at The University of Texas M. D. Anderson Cancer Center, and evaluated the combination of INGN 241 and radiation treatment in mice implanted with human NSCLC tumors. Results demonstrated a substantial and prolonged inhibition of tumor growth following the combined treatment. Analysis of tumors revealed a significant reduction in two proteins (bFGF and VEGF) that regulate the formation of new blood vessels essential for tumor growth as well as a reduction in the number of small blood vessels and an increase in apoptosis in tumors treated with the combination regimen compared with either INGN 241 or radiation alone. Additional data show that MDA-7 protein sensitizes the cells that give rise to new blood vessels to the effects of radiation without affecting other normal cells. "In addition to being able to cure some animals with human lung tumors, we found a greater than 300 percent increase in survival after treatment with INGN 241 and radiation combination therapy," said Dr. Meyn. "This treatment regimen kills tumor cells directly and then kills the vasculature feeding tumors without evidence of toxicity. We evaluated the critical molecules involved in angiogenesis and demonstrated that the combination of INGN 241 and radiotherapy significantly suppressed their activity. This data provides an impetus to evaluate INGN 241 in combination with radiotherapy in patients with lung cancer." Postop chemo boosts lung cancer survival Adjuvant therapy significantly improves lifespan in patients with early-stage lung cancer compared to surgery alone-(Yahoo News-05/06/2004) Two "paradigm shifting" studies presented at this year's American Society of Clinical Oncology meeting here show that adjuvant chemotherapy following surgery significantly improves survival in patients with early stage lung cancer compared to surgery alone. In one study, researchers funded by the National Cancer Institute of Canada (NCIC) found that postoperative treatment with the drugs vinorelbine and cisplatin increased the overall survival of patients with early non-small cell lung cancer (NSCLC) by 15% after five years. The other study, conducted by U.S. researchers for the Report of Cancer and Leukemia Group B (CALGB), was halted early after it found that the chemotherapy regimen of paclitaxel and carboplatin improved four-year overall survival by 12% following surgical resection in early-stage disease. "This is the best news for lung cancer patients in a long time," said lead NCIC investigator Dr. Timothy Winton of the University of Alberta in Edmonton. "I think the collective data from these studies is quite telling and compelling as a move towards a change in the standard of care." "These two trials show a large benefit comparable to what we've seen recently in breast cancer and colorectal cancer," said lead CALGB investigator Dr. Gary Strauss of the Rhode Island Hospital and George Brown Medical School in Providence, RI. In the NCIC study, Dr. Winton and colleagues compared the effectiveness of a 16-week regimen of combined neoadjuvant cisplatin and vinorelbine post surgery versus surgery alone (the current standard of care) in 482 patients (age 61 years; 65% male) with stage I or II NSCLC that had been completely removed. The mean survival was found to be significantly longer in the chemotherapy plus surgery group (94 months) than in the group who received surgery alone (73 months). The time it took for a patient's disease to recur was also longer in the chemotherapy plus surgery group. Many did not experience a recurrence during the study period compared to an average time to recurrence of 46.7 months in the surgery alone group. At five years, more patients in the chemotherapy plus surgery group than the surgery alone had survived longer (69% vs. 54%, respectively). "The important, good news for lung cancer patients that came out of this trial is that toxicity to this regimen was limited," said Dr. Winton. "The quality-of-life data that we have show that there was some intrusion in quality of life during the treatment, but that these patients that were treated recovered and had excellent quality of life in the longer term." The commonest non-hematologic toxicities in the study were fatigue (77%), nausea (76%), anorexia (53%), vomiting (46%), sensory neuropathy (45%) and constipation (44%). Two patients died of drug-related toxicities, which were febrile neutropenia and pulmonary fibrosis. In the CALGB study by Dr. Strauss and colleagues, 344 patients with stage IB NSCLC (with tumours at least 3 cm in diameter) who had undergone complete surgical removal of the tumour were randomized to receive adjuvant chemotherapy with paclitaxel and carboplatin or to no further treatment after surgery. The findings showed that overall survival was significantly better for the 173 patients who received the adjuvant chemotherapy. At four years, there was an absolute overall survival benefit of 71% in the chemotherapy group versus 59% in the surgery alone group. Lung cancer mortality at four years was 15% and 26% in the chemotherapy and surgery only groups, respectively. This translated into a 38% reduction in mortality from all causes specifically favouring chemotherapy. At the time of the meeting here, there were 19 lung cancer deaths in the chemotherapy group and 34 deaths from lung cancer in the control group. The researchers noted adjuvant chemotherapy was well tolerated, and there were no chemotherapy-related toxic deaths. "The results of this study represent an important development in the management of patients with early-stage lung cancer," Dr. Strauss said. "The positive results using a carboplatin combination are of particular interest, since many oncologists see carboplatin-based therapy as better tolerated than cisplatin regimens in NSCLC patients." At a press conference here, Dr. Frances Shepherd, Scott Taylor Chair in Lung Cancer Research at Toronto's Princess Margaret Hospital, described Dr. Winton's and Dr. Strauss's studies as "paradigm shifting." Their findings should convince the oncology community that adjuvant chemotherapy for completely resected patients with NSCLC should now be the standard of care, she said. The only current treatment for patients with early stage NSCLC is the surgical removal of the tumour, but patients often experience recurrence of the disease, which often does not respond to treatment. NSCLC is the most common type of lung cancer, accounting for more than 80% of all lung cancer Why lung cancer in women is different from men-(Yahoo News-03/06/2004) Noting that lung cancer is women's number one cancer killer, Loyola medical oncologist Dr. Kathy S. Albain will speak on the molecular differences in lung cancer between men and women at the annual meeting of Women Against Lung Cancer, a Professional Alliance for Education and Research (WALC), at the Hilton New Orleans Riverside Hotel, Two Poydras Street, New Orleans. "Lung cancer takes more women's lives than reproductive cancers and breast cancer combined," said Albain, WALC vice president and professor, division of hematology/oncology, Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, Ill. "We must devote more resources to battling this devastating disease." Albain is calling for more research funding targeted to examining why lung cancer is so deadly and why it affects men and women so differently. "Cigarette smoke damages women's lungs more than men's lungs and lung cancer treatment affects women differently than men," said Albain, director, Breast Research Program; co-director of the multidisciplinary Breast Oncology Center; and director of the Thoracic Oncology Program, Cardinal Bernardin Cancer Center, Loyola University Health System, Maywood, Ill. Albain has been a principal or senior investigator for major national and international research into treating breast and lung cancer. Women Against Lung Cancer was established in 2001 to educate the public and health care professionals about the magnitude of the lung cancer problem in women. WALC supports and encourages research in gender-related differences in the causes, treatments and prevention of lung cancer. WALC also mentors women health care professionals to pursue careers in lung cancer research. The WALC board is composed of leading women oncology health care professionals in the United States and Canada, along with members of women's advocacy groups and the lay public. A new way to kill cancer: SLU research shows viruses can destroy lung, colon tumors-(Yahoo News-15/05/2004) A genetically engineered virus can selectively kill cancerous cells in the lung and colon while leaving healthy cells intact, according to new research published in Cancer Research by William Wold and colleagues at Saint Louis University School of Medicine. The research could lead to a new class of cancer therapies that selectively kill cancer cells. "These engineered viruses kill cancer cells through a mechanism that is completely different from chemotherapy or radiation," said Dr. William Wold, chair of the department of molecular microbiology and immunology at Saint Louis University School of Medicine. "These viruses have the potential to treat many cancers that are resistant to currently available therapeutics. It also may be possible to use these viruses in combination with other therapies to create novel treatment regimens." Dr. Wold and his colleagues Karoly Toth, Konstantin Doronin, Ann E. Tollefson, Mohan Kuppuswamy, Baoling Ying, Jacqueline Spencer, and Maria Thomas have been researching for many years ways to convert the relatively benign "adenovirus" that causes symptoms similar to the common cold in children into an anti-cancer drug that attacks and destroys cancerous cells. Wold's group has developed several new "adenovirus cancer gene therapy vectors," changing these genes so the virus will attack cancer cells. "Some of our vectors are designed to destroy many different types of cancers, others are designed to be specific to colon or lung cancer. In preclinical testing these vectors were highly effective against cancerous tumors and did not harm normal tissues." The new research reported in Cancer Research involves INGN 007 (VRX-007) and INGN 009 (VRX-009), two novel "oncolytic adenoviruses" that have been engineered to kill cancer cells via viral replication. These viruses can be engineered so that they are active in specific types of cancer cells. The data published indicate that both efficiently killed cancer cells in culture. Specifically: · INGN 009, which has been designed to kill cells that carry a mutation common in many colon cancers, efficiently killed cultured colon cancer cells, but not lung cancer cells. · INGN 007 effectively killed both types of cancer cells. In an animal model of colon cancer, injection of either INGN 007 or INGN 009 into tumors suppressed tumor growth more efficiently than a negative control (five-fold and ten-fold suppression, respectively). · INGN 007 also completely suppressed tumor growth in a lung cancer model of disease. Introgen Publishes Data Describing Novel Mechanism of mda-7 Anti-Cancer Activity-(PRNewswire-26/04/2004) Results of a new preclinical study evaluating the mechanisms by which mda-7/IL-24, the active component of Introgen's (Nasdaq: INGN) INGN 241, kills non-small cell lung cancer cells have been published in Molecular Therapy, the official journal of the American Society of Gene Therapy. Data from these studies, which were conducted in collaboration with researchers at The University of Texas M. D. Anderson Cancer Center, Baylor College of Medicine and The University of Texas Medical Branch at Galveston, identify a novel intracellular pathway through which mda-7/IL-24 causes lung cancer cells to undergo apoptosis (programmed cell death). Additionally, these studies highlight the ability of mda-7/IL-24 to exert its anti-cancer effects through a variety of pathways, depending on the gene expression patterns of various types of cancer cells. Dr. Sunil Chada, Ph.D., Introgen's director of research and development, said, "These data identify a unique intracellular signal by which INGN 241 kills cancer cells. Expression of MDA-7 protein inside a cancer cell by treatment with INGN 241 activates a stress response pathway that results in selective apoptosis in cancer cells. These studies demonstrate that INGN 241 can work through multiple pathways to kill cancer cells, without exhibiting toxicity to normal cells. Cancer cells can mutate to develop resistance to chemotherapy and radiation therapy -- MDA-7 is unusual in that it can attack cancer cells via multiple mechanisms and thus may be a good candidate for cancers resistant to conventional therapies. The multiple anti-cancer activities of INGN 241 suggest that this product candidate may have utility in treating a broad array of cancers." In the published study, researchers evaluated the role of MDA-7 protein inside and outside tumor cells. The presence of MDA-7 protein in a specific part of the cancer cell involved in secretion activates a stress response that ultimately leads to cell death. This is a previously unknown mechanism for tumor cell killing. In the lung cancer cells tested, the killing was caused by intracellular MDA-7 since these cells lack MDA-7 receptors on their cell surface. Other tumor cells express specific receptors for MDA-7 on their cell surface and can be killed by both intracellular and extracellular mechanisms that are induced in cancer cells. This study underscores the tumor cell selectivity of the tumor killing mechanisms of INGN 241. Dr. Robert E. Sobol, Introgen's senior vice president of medical and scientific affairs said, "Patients with lung cancer have limited treatment options. The identification of a novel pathway for selectively inducing cell death in lung cancer cells may enable us to develop innovative approaches to therapy. To date, our clinical trials of INGN 241 have shown us that the INGN 241 product candidate has favorable safety and tolerability profiles and have provided data to support continued clinical development in lung cancer and other cancer indications." New Research to Address Pressing Question: Will Early Lung Cancer Detection Lead to Tobacco Cessation?-(Yahoo News-26/04/2004) A new screening technology that could detect lung cancer much earlier than ever before was funded through matching grants of $1.8 million respectively from the American Legacy Foundation and the UK's Medicsight Foundation. Weill Medical College of Cornell University, an international leader in CT screening for lung-cancer detection, will conduct the research. The donation will support a 4,000-patient study whose goal is to demonstrate that CT screening for lung cancer can be effectively linked to smoking-cessation programs to enhance the motivation for people to stop smoking. The study, which will begin in June, will use unique advanced image analysis software. "We want to make screening programs an economic and life-saving reality," says Dr. Claudia Henschke, the study's principal investigator and one of the world's leading authorities on CT screening for lung cancer. "The International Early Lung Cancer Action Program (I-ELCAP) is proving that CT screening is an effective tool for early diagnosis of lung cancer. This newly funded study represents a unique opportunity to understand how to best increase smoking cessation in the context of CT screening. At the same time, we will be incorporating and developing advanced image processing software to make screening as effective as possible." Dr. Henschke directs the Lung Cancer Screening Program at New York-Presbyterian Hospital/Weill Cornell Medical Center, where she is professor of radiology and division chief of chest imaging. The American Legacy Foundation - the only national organization solely focused on tobacco prevention and cessation - and Medicsight Foundation, which provides research funds for medical imaging, share Dr. Henschke's interest in determining if participation in early detection programs would lead more smokers to quit. "The American Legacy Foundation knows that science eventually will find far better ways to detect and treat lung cancer," said Cheryl G. Healton, Dr. P.H, and president and CEO of the Foundation. "The pressing question in the minds of many is whether or not CT screenings for lung cancer will encourage smokers to quit or make them put off this decision even longer. With lung cancer being the leading cause of cancer death in this nation, the Foundation is especially interested in answering this vexing question." "The Medicsight Foundation recognizes the need for teamwork in lung cancer. We know that primarily lung cancer is the result of smoking," Rockefeller says, "but we also know that smokers need help - and teamwork - if they are to succeed in breaking their damaging addiction. When you go it alone, you have a one in 12 chance of stopping smoking. Support can improve that chance." Lung cancer 'different in women-(Yahoo News-13/04/2004) Lung cancer is a different disease in women than it is in men, researchers have said. The female hormone oestrogen is partly to blame, according to a team at Northwestern University, Illinois. Rates of lung cancer in women have increased significantly in recent decades while those for men have remained stable. The research in the Journal of the American Medical Association also noted the effect of more women smoking. Female smokers have a greater chance of developing lung cancer, and a higher risk of developing adenocarcinoma, which is the most common form of the disease. But women also have better survival rates, the researchers said.Numbers of women smoking continue to increase, while rates among men are falling. Between 1990 and 2003 there was a 60% increase in lung cancer cases among women in the US. An estimated 68,500 American women will die from the disease this year. The team at Northwestern University, and colleagues at Memorial Sloan-Kettering Cancer Center, New York, looked at previous research into lung cancer and found evidence that the differences in disease rates and survival could in part be due to oestrogen. Studies have shown lung cancer cells have more oestrogen receptors on their surface than normal lung cells. Other research has indicated a link between oestrogen replacement therapy and adenocarcinoma and an interaction with smoking. Dr Jyoti Patel, an oncologist at the university, said: "Lung cancer appears to be a different disease in women. "Mounting evidence suggests that these differences could be due, in part, to oestrogen. "Genetic, metabolic and hormonal factors all are important to the way women react to carcinogens and lung cancer." The researchers said women reacted better to some targeted therapies and they were now trying to work out why that was. Professor Michael Seckl, professor of cancer medicine at Imperial College London, has researched the role of oestrogen and found a possible link in lung cancer patients. He said the conclusion that the hormone was partly to blame for women's different rates of disease and survival was a "plausible interpretation". Professor Seckl added: "It is hardly surprising - men and women are very different. "The message needs to get out there that lung cancer is not just a male disease. Women do appear to be more at risk of lung cancer." Far more research into lung cancer was needed, he said, as it currently gets only 3% of cancer research money in the UK though it is the form of the disease that kills the most people More US women die from lung cancer-(Yahoo News-14/04/2004) Deaths of American women from lung cancer have shot up 600% in the past 50 years, according to new research. During the same period, the number of lung cancer deaths in men declined. The trend mirrors a dramatic increase in tobacco use by women in the United States during the 20th century. But the findings can not simply be explained by the number of women smoking, said scientists. They also pointed to biological differences that may make women more susceptible to some forms of lung cancer than men. Researcher Dr Jyoti Patel, from North-western University in Chicago, said: "Genetic, metabolic and hormonal factors are all important to the way women react to carcinogens and lung cancer. This information should impact how we evaluate and screen patients who smoke and how we direct smoking cessation and lung cancer prevention programmes." Lung cancer had now surpassed breast cancer as the leading cause of cancer death among American women, said the researchers. The disease accounted for a fourth of all female cancer deaths in the United States last year. This year, lung cancer was expected to kill 68,500 American women, equal to the number dying from breast and all gynaecological cancers combined. British women more likely to die of cancer-(Yahoo News-04/04/2004) British women are at a much higher risk of dying from cancer than those in many other European countries including Estonia, Slovenia, and Russia, according to research published by the European Institute of Oncology. The cancer mortality rate for women in England and Wales is almost double that of Greece which is at the healthier end of a league table of 37 European countries. Female deaths from lung and bladder cancer in Scotland are the highest in Europe. The study also reveals mortality from lung cancer among women in Scotland is seven times that of Spain. England and Wales rank fifth. The figures will raise further alarm over failure of health services to deal effectively with breast cancer. Scotland, and England and Wales, have the seventh and eighth highest death rates for breast cancer, according to the study. But the study shows death rates from cancer for men are below the European average. The gender gap has been created largely by poor outcomes for women in three main areas of the disease - breast, lung and bladder cancer. Meanwhile, there have been huge improvements in treatment of male cancers, with 96 per cent of men with testicular cancer in the UK now surviving more than five years. The research suggests that while death rates from cancer have been going down across Europe - 90,000 fewer deaths a year than in the late 1980s - there are big differences between countries. Out of 37 countries surveyed, Scotland has the third highest overall cancer death rates for women, just behind Denmark and Hungary. Ireland is fifth while England and Wales are seventh highest. Scotland also tops the league for bladder cancer, with England and Wales in third place. The Scottish death rate is around four times higher than Finland, at the bottom of the league. A report in the International Journal of Cancer says that to reduce death rates, concerted action is needed. "The maintenance, and potential improvement, of favourable trends in cancer mortality in the near future require an integrated strategy focusing on control of tobacco, alcohol abuse and other major risk factors, including avoidance of obesity, taking up of physical activity, favourable changes in diet, increasing daily intake and variety of vegetables and fruit, and avoiding excessive sun and other sources of UV exposure," it says. The report says that in the European Union, total cancer mortality declined by 7 per cent for both sexes over the last five-year period they looked at. It says that the decline is largely due to the drop in tobacco-related cancer mortality in men Concurrent Chemoradiotherapy Provides Good Local-Regional Control and Long-Term Survival in Patients with Stage III Non Small-Cell Lung Cancer-(Yahoo News-18/03/2004) Concurrent chemotherapy with carboplatin/paclitaxel and radiation therapy provides excellent local-regional control (LRC) and encouraging long-term survival in patients with stage III non small-cell lung cancer (NSCLC), according to the findings of new research. In the past decade, the University of Pennsylvania Medical Center, Philadelphia, United States, has offered neoadjuvant chemoradiotherapy to selected stage III NSCLC patients with clinically apparent N2 disease or other features that raised doubts about complete resectability. In the current analysis, Mitchell Machtay, MD, and colleagues present the short-term and long-term outcomes (pathologic response, toxicity, LRC, and survival) of patients treated with neoadjuvant chemoradiotherapy and planned operation for stage IIIA disease. Patients underwent pretreatment evaluation between 1993 and 2000; 87% had complete mediastinoscopy staging, and all were believed to be poor candidates for up-front operation because of bulky extent of disease. Radiotherapy consisted of conventional, 2-dimensionally planned treatment to 45 to 54 Gy in 1.8- to 2-Gy fraction size. Concurrent chemotherapy consisted of etoposide/cisplatin or carboplatin/paclitaxel. Out of 53 patients, 85% were deemed surgical candidates after induction therapy. Twenty-two (42% of the initial cohort) had a major pathologic response to stage 0, I, or II disease. The 5-year actuarial survival was 31%, and improved survival was associated with major pathologic response (48% vs. 24%; P = .027). The overall rate of early death potentially related to therapy was 9%, and was most often seen in patients who underwent right pneumonectomy. Efficacy and mortality in patients receiving etoposide/cisplatin and radiotherapy versus carboplatin/paclitaxel and radiotherapy were similar. However, the latter regimen was associated with less grade 3 or higher acute toxicity requiring interruption or hospitalisation during neoadjuvant treatment (P =.02). LRC was achieved in 83% of all patients (90% of the patients who underwent resection). The first site of treatment failure was brain metastases in 23% of patients. "Our study shows that the resectability rates and LRC for stage IIIA NSCLC treated with neoadjuvant chemoradiotherapy are high," Dr. Machtay and colleagues conclude. "It is disappointing that the overall survival and relapse-free survival have not improved appreciably over the past decade," the researchers note. "This mainly reflects the inadequacy of current therapies to sterilize micrometastatic disease, including brain metastases," they add. Blowing Up Lung Cancer-(ET-20/02/2004) University of Alberta researchers have created "nanoparticle cluster bombs" that carry lung cancer drugs directly to their target. The treatment system has proven effective in treating cancerous cells in a laboratory petri dish and the researchers will conduct tests in live laboratory specimens this year. Clinical trials would follow that. "Based on what we've been able to do so far, we have practical hopes that a new lung delivery platform for lung cancer can be established," researcher Dr. Raimar Loebenberg, a professor of pharmacy, says in a prepared statement. The lung cancer drug, in powder form, is loaded into an inhaler that's similar to the device used by people with asthma. Each grain of the powder contains thousands of nanoparticles. When the powder is inhaled and arrives in the lungs, it dissolves and the nanoparticles are released. "Once the nanoparticles are active in the lung, they have a tremendous advantage over regular drugs, because they are better able to do exactly what we want them to," Warren Finlay, a mechanical engineering professor, says in a prepared statement. The nanoparticles can be designed to escape detection by the immune system and to carry designer drugs that target cancer cells and leave healthy cells alone. "This drug and this delivery system have a lot of potential-there are a lot of different things we can do as we're able to control where and when the nanoparticles release their payload," Finlay says. The research appears in a recent issue of the International Journal of Pharmaceuticals Experimental Vaccine May Stop Lung Cancer-(Yahoo News-13/02/2004) An experimental vaccine wiped out lung cancer in some patients and slowed its spread in others in a small but promising study, researchers say. Three patients injected with the vaccine, GVAX, had no recurrence of lung cancer for more than three years afterward, according to the study of 43 people with the most common form of the disease, non-small cell lung cancer. The findings were published in the Journal of the National Cancer Institute. The research was funded in part by Cell Genesys, a pharmaceutical company that hopes to produce the vaccine. The vaccine, developed by researchers at Baylor University Medical Center in Dallas, is years away from reaching the market, if ever. The researchers hope to apply for Food and Drug Administration approval in three years. "The results are very promising for patients with non-small (cell) lung cancer, which is frequently resistant to chemotherapy," said Dr. John Nemunaitis, a Baylor oncologist who led the study. Non-small cell lung cancer is the nation's leading cause of cancer death, killing more than 150,000 people each year. The disease is related to smoking and is often difficult to treat. Treatment usually involves removal of the tumor, chemotherapy or both. Vaccine studies are a burgeoning area of cancer research. Unlike traditional vaccines, which generally aim to prevent disease, some experimental cancer vaccines are designed to treat or cure existing disease. This study is the first to show complete and long-lasting regression of lung cancer by stimulating the immune system to attack cancer cells, Nemunaitis said. A similar approach has shown promise against skin and renal cell cancer. In the study, each patient was injected in the arm and leg with a vaccine that included cells from his or her tumors. A gene called CM-CSF was placed into the cancer cells to change the surface of the cells to help the body identify them as cancerous. The body's immune cells soon began to recognize, attack and destroy the cancer cells in the lungs. Forty-three lung cancer patients - 10 in the early stage and 33 in the advanced stage - were injected with the vaccine every two weeks for three months. Researchers followed them for three years. The cancer disappeared in three of the advanced-stage patients. Two of those patients previously had chemotherapy, which failed. In the rest of the advanced-stage patients, the disease remained stable and did not spread for almost five months to more than two years. For patients in the early stage, the vaccine did not make much difference against the cancer. "The most exciting thing is in those who responded to the vaccine, it was complete," Nemunaitis said. "It's given us a lot of encouragement." For patients with advanced-stage lung cancer, chemotherapy works no more than 3 percent of the time, and survival is usually eight to nine months. Those whose cancer went into remission with the vaccine were alive at least three years later. And the vaccine has no side effects, Nemunaitis said. Dr. Anwar Khurshid, an oncologist at the Arlington Cancer Center, said the findings will "open a lot of avenues." "I think you'll cure some patients but not everyone. That's what has been proven in other cases," he said. "You need to vaccine earlier or combine with something else to cure more people. Lung Cancer Risk May Be Higher in Female Smokers-(Reuters Health-05/02/2004) Female smokers may be more likely to develop lung cancer than men who smoke a similar amount, new study findings suggest. The investigators found that of nearly 2,500 men and women age 40 and older screened for lung cancer, women had more than twice the risk of being diagnosed with the disease. If further research confirms this higher risk, it will be particularly important to stop girls and young women from taking up the smoking habit, the researchers say. There's not yet a clear reason why women might face a higher lung cancer risk than men, according to the study's lead author, Dr. Claudia Henschke of New York-Presbyterian Hospital/Weill Cornell Medical Center in New York. It's possible, she noted in an interview, that women are less able than men to metabolize, or "clear," the toxins from tobacco smoke, but more research is needed to answer that question. Other possibilities-such as sex differences in the aggressiveness of lung tumors, or underreporting of smoking levels by women-do not appear to explain the findings, according to Henschke. She and colleague Dr. Olli S. Miettnen report their results in the journal Lung Cancer. In the study, 1,202 women and 1,288 men underwent computed tomography (CT) scans to screen for lung cancer. All had smoked for at least 10 "pack-years"-meaning, for example, one pack a day for 10 years, or two packs a day for five years. Follow-up testing confirmed 45 cases of lung cancer among women, and 20 among men. After the researchers factored in participants' age and smoking history, women were more than twice as likely as men to be diagnosed with lung cancer. Some past research has suggested female smokers might be more susceptible to developing lung cancer, but other studies have failed to find such evidence. If further research confirms the current findings, it will be especially important for anti-smoking efforts to reach women and girls, according to Henschke. "The key thing," she said, "is that girls and young women don't start smoking." Drug Shows Little Promise Vs. Lung Cancer-(AP-13/01/2004) A drug that has prolonged the lives of many breast cancer patients has failed to live up to hopes that it might help people with lung cancer, new research has found. In a study outlined in the European journal Annals of Oncology, those treated with Herceptin in combination with two chemotherapy medicines did no better than patients treated with the chemotherapy drugs alone. However, the study, involving about 100 lung cancer patients, gave a hint that a very small fraction of patients with a particular genetic profile may benefit. Herceptin, a standard treatment for spreading breast cancer, belongs to a new set of cancer drugs called targeted therapies, which are intended to arrest cancer by disrupting the internal signals that fuel its unruly growth. Herceptin targets a gene called HER-2 and its protein. In breast cancer it typically delays progression by a few months in the quarter of victims with a particular genetic profile. Scientists were hopeful that Herceptin might benefit lung cancer patients because in many the HER-2 gene is switched on. Also, test tube studies had shown the drug seemed to work better in a chemotherapy combination on lung cancer cells than it did on breast cancer cells. "It was very disappointing therefore to find that the survival times and the time to the disease progressing were very similar - between six and seven months for both," said the study's leader, Dr. Ulrich Gatzemeier, head of thoracic oncology at Grosshansdorf Hospital in Germany. Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, said the findings show that for the large majority of lung cancer patients, Herceptin is not going to be the answer. "Positive or negative, this is important information," he said. "We now know a lot more than we did before this trial was done. This type of information will provide significant guidance to others." "We are perhaps at the end of the beginning of using targeted therapies," said Lichtenfeld, who was not involved with the research. "We're still learning about how these cells work. We are still finding the targets that we have to test. We're going to get there, it's just taking us a longer time." However, the study found that five of the six patients who had extremely high levels of the HER-2 protein responded to the drug better than the other patients did. It was nearly 8 1/2 months before their disease progressed compared with just over six months for the patients with lower HER-2 levels, Gatzemeier said. But experts say the fraction of patients who could benefit is so small that limited resources may better be directed elsewhere. Another targeted drug, Iressa, also has failed to show a benefit as a mainline lung cancer medicine. Lung Cancer Screening Helps Smokers Kick the Habit-(Reuters Health-20/10/2003) Getting screened for lung cancer helps provide many smokers with enough motivation to quit the habit out for good, new research suggests. Researchers based at the Mayo Clinic in Rochester, Minnesota, found that 14 percent of smokers had stopped smoking one year after being screened for lung cancer -- a much higher quitting rate than that typically seen in smokers who are not screened for cancer. Nearly 90 percent of lung cancers are caused by smoking, and smokers whose screening tests showed they had sub-par lung function were more likely to quit than smokers who learned their lungs were less damaged by their habit. The report, which appears in the journal Cancer, suggests that lung cancer screening provides healthcare providers with an opportunity to help smokers realize the impact of their habit, and how to get help, the authors note. "These findings support the use of cancer screening as a teachable moment in which to build on a patient's openness to learn new information and heightened motivation to promote health by providing tobacco dependence intervention," the authors write. During the study, the authors, led by Dr. Lisa Sanderson Cox, screened 901 smokers and 574 former smokers for lung cancer, then asked them one year later if they were still smoking. All former smokers said they had quit within the past 10 years, and both current and former smokers said they had smoked the equivalent of at least one pack per day for 20 years. Study participants received a chest CT scan to get a detailed image of the lungs. Typically, only between 5 and 7 percent of smokers who quit manage to stick it out for a year. However, two times as many butted out for good after being screened for lung cancer. On the other hand, ten percent of former smokers in the study said they had picked up smoking again one year after being screened. This shows "that clinicians promoting smoking abstinence with screening participants must not overlook relapse prevention in former smokers, particularly those in the early period of abstinence," Sanderson Cox and her team write. Ethyol® Protects Against Side Effects of Treatment in Non-Small Cell Lung Cancer-(ET-23/09/2003) According to results published in the International Journal of Radiation, Oncology, Biology and Physics, Ethyol® (amifostine) provides protection against side effects caused by treatment with radiation and chemotherapy, without compromising the effectiveness of therapy in patients with non-small cell lung cancer. Treatment for cancer with radiation and/or chemotherapy is associated with the development of various side effects, depending upon the chemotherapy agents used, the location of radiation, the doses and scheduling of particular regimens as well as the individual patient. Side effects can range from mild to severe, and may even become life threatening. If side effects from treatment become severe enough, the quality of life of a patient becomes impaired, and treatment doses often have to be delayed or reduced, compromising the effectiveness of therapy altogether. Research efforts have become more focused on reducing or mitigating side effects caused by treatment so that doses producing optimal outcomes may be delivered and patient quality of life be maintained. Ethyol is an agent that is approved by the FDA for the prevention or reduction of xerostomia (dry mouth) in patients receiving radiation therapy for cancers of the head and neck, and for the prevention or reduction of renal (kidney) side effects caused by Platinol® (cisplatin) in patients with advanced ovarian or non-small cell lung cancer (NSCLC). Clinical trials have also demonstrated that Ethyol reduces the incidence of side effects of the bladder and gastrointestinal track in patients receiving radiation to the pelvis. Clinical trials are ongoing to evaluate Ethyol in preventing or reducing side effects from various treatments in several types of cancer. Researchers from Greece recently conducted a clinical trial evaluating Ethyol in the treatment of NSCLC. This trial involved 73 patients with advanced NSCLC who were receiving radiation plus chemotherapy (radiochemotherapy) with a platinum compound (Platinol or Paraplatin®). Patients received radiochemotherapy (RCT) plus Ethyol or RCT only (control group) and were directly compared. The incidence of severe esophagitis (inflammation of the esophagus) occurred in only 39% of patients receiving Ethyol, compared with 84.4% in the control group. There was also a significant reduction in side effects to the lungs in the group of patients treated with Ethyol (19.4%), compared to the control group (56.3%). Furthermore, anti-cancer responses to treatment were not compromised with the treatment of Ethyol, with an 88.8% anti-cancer response rate in patients treated with Ethyol and an 82.2% anti-cancer response rate in those treated with RCT alone. The researchers concluded that the addition of Ethyol to radiochemotherapy for treatment of advanced NSCLC reduces the incidence of esophagitis and side effects affecting the lungs without compromising the effectiveness of treatment. Longer follow-up may help determine if a survival benefit can be achieved with the use of Ethyol. Patients with NSCLC who are scheduled to undergo radiochemotherapy may wish to speak with their physician about the risks and benefits of Ethyol. Age No Bar to Chemotherapy for Lung Cancer-(Reuters Health-29/08/2003) Chemotherapy commonly used to treat lung cancer is as effective and is no more toxic for the elderly than for younger patients, researchers report in the medical journal Cancer. In fact, Dr. Thomas A. Hensing told Reuters Health, his group's research matches that of others showing that "age alone should not be used to determine treatment for patients with advanced lung cancer. Elderly patients who are fit and active should be offered standard therapy or encouraged to enroll in ongoing clinical trials for this disease." Advanced lung cancer is increasingly seen in people 70 years old and older, but they are less likely to be considered for the same treatment used in younger individuals. However, research shows that patients who are relatively healthy apart from their cancer survive as long as their younger counterparts, with a comparable quality of life. Hensing, who is currently with Evanston Northwestern Healthcare in Evanston, Illinois, and colleagues analyzed the results of a trial involving 239 patients who had advanced "non-small-cell" lung cancer, nearly a third of whom were aged 70 or above. All the patients were treated with a combination of carboplatin and paclitaxel. Older patients were no more likely to suffer from severe nausea and vomiting, nor did they have more muscle and joint pain. Blood disorders that often accompany chemotherapy, such as low levels of white blood cells, red blood cells and platelets, were no worse in the older patients. When responding to questionnaires asking about their quality of life, the older age group was similar to the younger one. Survival rates after |
