Lung Cancer

Avastin slows progression of lung cancer (Yahoo News-15/09/2008) 

The results of a study presented on Monday show that Avastin combined with gemcitabine-cisplatin chemotherapy improves the time lung cancer patients live without progression of the disease, according to Swiss drugmaker Roche. There was also a positive trend to extended survival. Patients with previously untreated, advanced non-small cell lung cancer (NSCLC) survived up to 30 percent longer without disease progression when Avastin was added to the treatment regimen, according to a final analysis of the "Avail" trial presented at the European Society of Medical Oncology in Stockholm. The tumor response rate increased by up to 70 percent compared with chemotherapy alone, Roche added. Roche, which is a partner with Genentech in Avastin development, said the study was not powered to demonstrate an overall survival benefit. As a result -- as previously announced -- there was no statistically significant difference in survival between those who did and did not receive Avastin. But there were some encouraging signs. An exploratory analysis of overall survival in patients without second-line therapies showed a trend towards improvement of survival in patients given Avastin compared with those given chemotherapy alone, from 7.3 months to 8.7 months. All treatment groups in the study demonstrated an average overall survival of more than 13 months.

"Avail confirms for the second time that Avastin provides important clinical benefits and the longest survival reported for patients with advanced non-squamous NSCLC," said Christian Manegold of Heidelberg University in Mannheim, Germany, the principal investigator of the study. Avastin works by directly inhibiting vascular endothelial growth factor, a key mediator of the growth of new blood vessels. The lack of blood vessels prevents oxygen from reaching the tumor cells and they die. The drug is approved in different countries as a treatment for colorectal, lung, breast and kidney cancer.

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Asian lung cancer therapy studied (Yahoo News-17/09/2008)

Chinese medical scientists say the drug gefitinib (Iressa) should be considered the first-line therapy for non-smoking Asian patients with lung cancer. Asia has a high proportion of lung cancer patients who are non-smokers, a significant proportion of whom develop a form of cancer known as adenocarcinoma. "Around 50 percent to 60 percent of this population (has tumors) with mutations in the epidermal growth factor receptor and we know that patients with such mutations have a significantly better treatment outcome with gefitinib," said Professor Tony Mok from the Chinese University of Hong Kong. "Currently, gefitinib and other EGFR tyrosine kinase inhibitors are considered as second line therapy for advanced non-small-cell lung cancers, meaning the drugs should only be used after cancers fail to respond to the standard cytotoxic chemotherapy." Mok and his team studied 1,217 lung cancer patients who never received chemotherapy and had never smoked or were former light smokers. Half the group was treated with gefitinib or a combination of carboplatin and paclitaxel. The researchers found gefitinib was more tolerable and resulted in a greater likelihood of response. Mok presented his study this week in Sweden during a meeting of the European Society of Medical Oncology. 

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Study sheds light on lifelong nonsmokers and lung cancer (Yahoo News-10/09/2008)

The largest study of its kind to date sheds light on the 10 to 15 percent of lung cancers that are caused by factors other than tobacco smoking. The study analyzed data on lung cancer occurrence among lifelong nonsmokers in North America, Europe, and Asia and found that lung cancer death rates among never-smokers are highest among men, African Americans and Asians residing in Asia. Led by Dr. Michael J. Thun, an epidemiologist for the American Cancer Society, the study looked at data from nearly 2 million lung cancer deaths over the past several decades. "Lung cancer is obviously a significant public health and medical problem, even beyond the overwhelming disease burden caused by tobacco smoking," the researchers wrote. While the great majority of lung cancers are related to smoking, approximately 16,000 to 24,000 of the more than 161,000 lung cancer deaths each year are due to other factors. For comparison, if lung cancers not caused by smoking were considered a separate category, it would rank among the seven to nine most common fatal cancers in the U.S. The researchers say that as the number of never-smokers in the U.S. and other developed countries is increasing, the causes of lung cancer in such people is of particular interest and importance. To examine the issue, Thun's research team pooled data on lung cancer incidence and death rates among self-reported never-smokers from 13 large studies based in North America, Europe, and Asia that spanned the time period from 1960 to 2004. The pooled data involved nearly 2.5 million self-reported never smokers (men and women) from 13 large studies investigating the health of people in North America, Europe, and Asia.. The researchers also abstracted data for women from 22 cancer registries in 10 countries in time periods and regions where the smoking prevalence among women was known to be low. 

The researchers found that the incidence of lung cancer among lifelong nonsmokers was about equal to that of brain and other nervous system cancers. In terms of mortality, men who reported never smoking had a 1.1% risk of dying from lung cancer before age 85, with the corresponding estimate for women slightly lower at 0.8%. These mortality risks compare to estimates of 22.1% and 11.9% risk of dying from lung cancer for male and female current cigarette smokers, respectively.  While they lacked information on lung cancer death rates among Hispanic, Native American, and Asian never-smokers in North America, researchers did find evidence that lung cancer incidence and mortality are higher in African Americans and Asians residing in Asia than among those of European descent who have never smoked. The report also found no indication that lung cancer rates have changed among lifelong nonsmokers in the U.S. since the 1930s, failing to support assertions by other researchers that lung cancer risk has increased substantially in the United States in lifelong nonsmokers. 

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Study confirms Avastin lung-cancer benefits: Roche (Yahoo News-15/09/2008)

Swiss drugmaker Roche said that Phase III trial data showed Avastin combined with gemcitabine-cisplatin chemotherapy improved the time patients lived without lung cancer progressing. There was also a positive trend to extended survival. Patients with previously untreated, advanced non-small cell lung cancer (NSCLC) had an improvement of up to 30 percent in the time they lived without their disease progressing, according to a final analysis of the so-called Avail trial presented at the European Society of Medical Oncology in Stockholm. The tumor response rate was increased by up to 70 percent compared with chemotherapy alone, Roche added. Roche, which is a partner with Genentech on the blockbuster cancer treatment, said the study was not powered to demonstrate an overall survival benefit. As a result -- as previously announced -- there was no statistically significant difference in survival between those who did and did not receive Avastin. But there were some encouraging signs. An exploratory analysis of overall survival in patients without second-line therapies showed a trend towards improvement of survival in Avastin patients as compared to chemotherapy alone from 7.3 months to 8.7 months. All treatment groups in the study demonstrated a median overall survival of more than 13 months. "Avail confirms for the second time that Avastin provides important clinical benefits and the longest survival reported for patients with advanced non-squamous NSCLC," said Christian Manegold of Heidelberg University in Mannheim, Germany, the principal investigator of the study. Avastin works by directly inhibits vascular endothelial growth factor, a key mediator of the growth of new blood vessels. The drug is approved in different countries as a treatment for colorectal, lung, breast and kidney cancer.

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Immune System Biomarkers May Predict Early Lung Cancer (HealthDay News-15/09/2008)

A test that uses immune system biomarkers to detect lung cancer can identify the presence of the disease a year before diagnosis, long before a patient experiences any symptoms, according to researchers at the Fred Hutchinson Cancer Research Center in Seattle and the University of Michigan. They noted the immune system mounts a response against specific antigens, or proteins, produced by lung tumors in their early stages of development. "This kind of immune response won't necessarily kill the tumor, but it can act as a canary in a coal mine, signaling lung cancer at an early stage, before actual symptoms emerge. It is an important step toward developing a biomarker-based blood test for the early detection of lung cancer," Dr. Samir M. Hanash, head of the Molecular Diagnostic Program in the Public Health Sciences Division at the Hutchinson Center, said in a news release. Hanash and colleagues tested the sensitivity and specificity of three antigens linked to early stage, pre-symptomatic lung cancer -- annexin1, 14-3-3 theta, and LAMR1. The researchers used blood samples taken from 85 current or former smokers within a year of being diagnosed with lung cancer and blood samples from 85 current or former smokers who didn't develop lung cancer. The three antigens were found in the blood of 51 percent of the smokers who developed lung cancer and in 18 percent of those who didn't develop the disease. "The fact that we got a signal like this with just three biomarkers is very significant. If we enlarge this (biomarker) panel by adding a few more, we could develop a blood test with sufficient sensitivity and specificity for detecting lung cancer much earlier than current screening methods allow," Hanash said. Within five years, it may be possible to have a blood test that can be used in conjunction with CT scans and other imaging techniques to improve early detection of lung cancer in high-risk people, Hanash said. He also said this method may prove effective in early detection of other common kinds of cancer. "If we could identify those antigens that provide the best signature for not only lung cancer, but also for cancers of the colon, breast, prostate, ovary and the like, then with the tiniest drop of blood, we could have a screening test for all the common types of cancer to catch them at their earliest stages, when cure rates are high. That would be phenomenal," Hanash said.

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Doctors extract cancer cells from blood sample (Yahoo News-02/07/2008)

An experimental process that snags lung cancer cells from a blood sample could give doctors real-time feedback on the most effective therapy, researchers reported on Wednesday. Dr. Daniel Haber of the Massachusetts General Hospital Cancer Center and Harvard Medical School and colleagues were able to extract blood-borne cancer cells from 27 volunteers with non-small-cell lung cancer that had spread. They found that changes in the number of circulating cancer cells correlated with the effectiveness of a patient's treatment and were also able to track genetic changes in the tumor cells over time. The study, reported on the Web site of the New England Journal of Medicine, is another step in the quest for individualized medicine, where doctors strive to quickly assess a tumor, choose the most effective treatment, and alter that treatment as cancer cells adapt. In December, the same group reported in Nature that their circulating tumor cells, or CTC, chip could extract malignant cells from people with breast, prostate, pancreatic and colorectal cancers, as well as lung tumors. Now they say they have used the collected cells to identify specific mutations, which may someday help guide therapy. "Right now you take your best guess as to what kind of treatment would work for a patient's cancer, give it to them for two or three months, and then repeat a CAT scan to see if it worked," Haber said in a telephone interview. 
CONTINUOUS MONITORING
"If there were a way of measuring an earlier response, that would be fantastic," he added. "The CTC chip offers the promise of non-invasive continuous monitoring." Doctors have many choices of drugs to treat lung cancer, the world's leading cancer killer, taking the lives of 1.2 million people a year -- 166,000 in the United States alone. Yet only 15 percent of patients live five years or more. "Treating patients with drugs specific to their particular tumor is likely to yield increased response rates, prolonged survival, and a decrease in the number of patients who are exposed to toxic drugs unnecessarily," Dr. Joan Schiller of the Lung Cancer Alliance wrote in a commentary. Schiller, of the University of Texas Southwestern Medical Center in Dallas, said there are practical questions about whether enough cells can be extracted to make the technique effective and whether it will work for other types of tumors.
Haber said he believes it will.

The CTC chip, licensed to the privately held CellPoint Diagnostics in Mountain View, California, is 100 times more sensitive than a U.S. Food and Drug Administration-approved technique that uses magnetic beads to try to extract cancer cells, according to Haber. The test requires a 10 milliliter blood sample -- just two teaspoons. It takes about eight hours to send the blood across the 80,000 tiny columns so a specially designed antibody glue can latch onto passing cancer cells. Haber said his team is trying to further automate the process to make it faster. "If the cells are alive on the chip, which they are, and if you have a new 'smart' drug that's supposed to attack a particular protein, you can test in the cell if the protein is being attached by the drug," he said.

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Faulty DNA repair could be a risk factor for lung cancer in nonsmokers (Yahoo News-26/06/2008)

People who have never smoked but whose cells cannot efficiently repair environmental insults to DNA are at higher risk of developing lung cancer than those with effective genomic repair capability, according to researchers from the Department of Epidemiology at The University of Texas M. D. Anderson Cancer Center. "About 15 percent of lung cancers occur in lifetime never smokers. Risk factors for lung cancer in people who have never smoked are poorly understood, but this study demonstrates that poor DNA repair capacity is an important predictor of lung cancer risk in never smokers," said the study's lead author, Olga Gorlova, Ph.D., an assistant professor in the Department of Epidemiology. In the June issue of Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research, the researchers say that, overall, nonsmokers with suboptimal DNA repair capacity (DRC) are almost twice as likely to develop lung cancer, compared with nonsmokers with normal DRC. Study participants with the lowest ability to repair their DNA had a more than a threefold increased risk, compared with individuals with efficient DRC. Secondhand smoke exposure is another established risk factor; in participants with inefficient DRC who also reported such exposure, the risk of lung cancer was almost fourfold. Although the research team has not pinpointed the gene or genes that cause suboptimal DRC, their data suggest that the trait is heritable to some degree. Notably they found that first-degree relatives of those with lowest DRC were 2.5 times more likely to develop lung cancer than were first-degree relatives of people with efficient DRC. "Our findings demonstrate that suboptimal DNA repair capacity together with secondhand smoke exposure are strong lung cancer risk factors in lifetime never smokers," Gorlova said.

This is the first study that has looked at functional DNA repair capacity as a risk factor for lung cancer in nonsmokers. Researchers drew white blood cells from 219 lung cancer patients and 309 matched control participants, all of whom had never smoked. They used the cells to conduct a host-cell reactivation assay, a complicated test that introduced a specific carcinogen, benzo[a]pyrene diol epoxide (BPDE) into the cells. BPDE is a hydrocarbon found in smoke of all kinds (tobacco, wood, etc.) that is highly carcinogenic and mutagenic, capable of changing the composition of DNA. The study is a continuation of research underway at M. D. Anderson that is looking for genetic and epigenetic components to lung cancer risk. The research group has previously shown that DNA repair capacity as measured by the host cell reactivation assay was significantly lower in lung cancer patients who were current or former smokers than in matched controls. "Many people think they aren't at risk for lung cancer because they don't smoke, but anyone who has non-smoking relatives with lung cancer should avoid not just tobacco smoke, but all the other carcinogens and mutagens that are products of combustion," Gorlova said.

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Cuba registers therapeutic vaccine for lung cancer (Yahoo News -26/06/2008)

THE first therapeutic vaccine for the treatment of advanced lung cancer has been registered in Cuba, the only one for this type of malignancy world-wide, reported the national news agency, AIN. Named CIMAVAX EGF, the antigen has been shown to be effective, extending patients’ survival and quality of life, said the doctor of biological science, Gisela González, manager of the project. The expert explained to the press that the drug was developed at the Molecular Immunology Center (CIM), one of the flagship institutions within Havana’s Scientific Pole. The first clinical trial was conducted in Cuba in 1995 with more than 400 patients with advanced lung cancer who had previously received conventional treatment with chemotherapy and radiation therapy, González indicated. The drug’s positive effects include a decrease or disappearance of shortness of breathe, weight gain, better appetite and controllable pain, allowing patients to participate in social life, she said. She explained that the vaccine which provokes an immune system response and does not have serious side-effects, is composed of two proteins, one from epidermal growth factor and the other, P-64 K, from cell membrane, both produced through DNA recombination methods by the Genetic Engineering and Biotechnology Center. González indicated that five Phase I trials have been conducted and two Phase II trials, one in Cuba and another in Canada and England.

The results of the Phase II trials showed clinical benefits for patients, as compared with those who did not receive the vaccine, leading to a registration request to the Cuban regulatory agency. González announced that in 11 hospitals within the country, a Phase III clinical trial is being conducted with 579 patients and that in August of this year Phase II trials will begin in Peru and subsequently in China. Dr. Tania Crombet, director of clinical research for CIM emphasized that Cuban scientists are investigating CIMAVAX EGF for other epidemoid (solid) cancers and have demonstrated its effectiveness in cases of neoplasia of the lung, head, neck, brain, stomach, breast, rectum, prostrate, cervix, bladder, ovary and pancreas. Cuba began studies of the new vaccine in 1992 which included pre-clinical trials with laboratory animals and, in 1995, conducted the first clinical trial.

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