PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

New targeted lung cancer drug produces 'dramatic' symptom improvement

Early-stage trial shows promise against tumors driven by ALK gene alteration

2010-10-28
(Press-News.org) A clinical trial of a potential new targeted treatment drug has provided powerful evidence that it can halt or reverse the growth of lung tumors characterized by a specific genetic abnormality. In their report in the October 28 New England Journal of Medicine, a multi-institutional research team reports that daily doses of the investigational drug crizotinib shrank the tumors of more than half of a group patients whose tumors were driven by alterations in the anaplastic lymphoma kinase (ALK) gene. In another one-third of study participants, crizotinib treatment suppressed tumor growth. Preliminary results of this study were reported at the June 2010 meeting of the American Society for Clinical Oncology.

"Traditionally phase 1 trials have been used to determine the safety of drugs that have never been given to people before," explains Eunice Kwak, MD, PhD, of the Massachusetts General Hospital (MGH) Cancer Center, corresponding author of the study. "In this trial we were always looking for patients whose tumors might be more likely to respond to this drug, since we knew it inhibited the cancer-related proteins ALK and MET. Fortunately, once the first stage of the trial had established the maximum tolerated dose, we had the flexibility to enroll additional patients whose tumors had these molecular abnormalities."

In recent years, cancer researchers have found that genetic abnormalities which spur uncontrolled cellular proliferation underlie several types of cancer. About 12 percent of the cases of non-small-cell lung cancer (NSCLC), the leading cause of cancer death in the U.S., are driven by mutations in a protein called EGFR, and several drugs that target the molecular pathway controlled by EGFR have halted or reversed tumor growth, at least temporarily. In 2007 it was discovered that a rearrangement involving the ALK gene, already associated with several other types of cancer, was behind 2 to 7 percent of NSCLC cases.

Laboratory studies at the MGH and other centers had shown that crizotinib could inhibit activity of both ALK and the MET oncogene, so the current study was designed in two parts. In the first stage patients with any solid tumor that had not responded to standard therapies received increasing daily oral doses of crizotinib to establish the highest dose that would not cause intolerable side effects. Two of the participants in that stage of the trial had ALK-altered NSCLC, and both of them showed what the investigators characterized as 'dramatic' symptom improvement. Based on those results, the second stage was expanded from three to a total of seven sites to enroll additional NSCLC patients with ALK-rearranged tumors.

Of 82 patients with ALK-altered tumors who eventually enrolled in the trial, crizotinib treatment reduced tumor size in at least 47 and halted tumor growth in 27. Among those participants, 63 have continued receiving the drug, some for more than two years. "This therapy is allowing patients to function without pain or a constant cough," Kwak explains. "The most rewarding thing about treating patients with this drug is watching them change from being completely controlled by their cancer to resuming a very normal life."

While results of the current study are promising, additional trials are required to confirm the effectiveness of crizotinib for NSCLC. A phase 3 clinical trial has started enrolling patients, and more information on that trial is available by calling the MGH Cancer Center at 877 789-6100. Kwak, an instructor in Medicine at Harvard Medical School, notes that the fact that the phase 3 trial started only three years after the phase 1 trial began – a process that took a decade for the first EGFR inhibitor – reflects the power of prospective tumor genotyping.

"The MGH already had the infrastructure in place to screen tumors for molecular abnormalities, so we were poised to test for ALK rearrangement," she explains. "We were actually able to identify the first patient with such a lung cancer and enroll him in the initial stage of this study four months after the original report of ALK-altered NSCLC was published. Then it was amazing to see his symptoms improve within a matter of weeks. These results are just one more compelling example of what we can do for our patients if we just learn more about their tumors."

INFORMATION:

The study was supported by Pfizer, which is developing crizotinib for clinical application, and by grants from the Aid for Cancer Research Foundation, the National Cancer Institute, the American Society for Clinical Oncology and other funders. Co-authors of the NEJM report include Alice Shaw, MD, PhD, Jeffrey Clark, MD, and John Iafrate, MD, PhD, MGH Cancer Center; Yung-Jue Bang, MD, PhD, Seoul National University College of Medicine, Korea; D. Ross Camidge, MD, PhD, University of Colorado Cancer Center; Benjamin Solomon, MB, BS, PhD, MacCallum Cancer Centre, Melbourne, Australia; Ravi Salgia, MD, PhD, University of Chicago; Robert Maki, MD, PhD, Memorial Sloan-Kettering Cancer Center; Sai-Hong Ou, MD, PhD, University of California, Irvine; Keith Wilner, PhD, Pfizer Pharmaceuticals; and Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute. Additional co-authors are based at the institutions named above and at Beth Israel Deaconess Medical Center.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $600 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

END



ELSE PRESS RELEASES FROM THIS DATE:

Into Africa? Fossils suggest earliest anthropoids colonized Africa

Into Africa? Fossils suggest earliest anthropoids colonized Africa
2010-10-28
Pittsburgh, Pennsylvania…Today in the journal Nature, a new discovery described by a team of international scientists, including Carnegie Museum of Natural History paleontologist Christopher Beard, suggests that anthropoids—the primate group that includes humans, apes, and monkeys—"colonized" Africa, rather than originally evolving in Africa as has been widely accepted. According to this paper, what is exceptional about these new fossils—discovered at the Dur At-Talah escarpment in central Libya—is the diversity of species present: the site includes three distinct families ...

Astronomers discover most massive neutron star yet known

2010-10-28
Astronomers using the National Science Foundation's Green Bank Telescope (GBT) have discovered the most massive neutron star yet found, a discovery with strong and wide-ranging impacts across several fields of physics and astrophysics. "This neutron star is twice as massive as our Sun. This is surprising, and that much mass means that several theoretical models for the internal composition of neutron stars now are ruled out," said Paul Demorest, of the National Radio Astronomy Observatory (NRAO). "This mass measurement also has implications for our understanding of all ...

New evidence supports 'Snowball Earth' as trigger for early animal evolution

New evidence supports Snowball Earth as trigger for early animal evolution
2010-10-28
RIVERSIDE, Calif. – A team of scientists, led by biogeochemists at the University of California, Riverside, has found new evidence linking "Snowball Earth" glacial events to the rise of early animals. The controversial Snowball Earth hypothesis posits that the Earth was covered from pole to pole by a thick sheet of ice lasting, on several occasions, for millions of years. These glaciations, the most severe in Earth history, occurred from 750 to 580 million years ago. The researchers argue that the oceans in the aftermath of these events were rich in phosphorus, a nutrient ...

Sodas, other sugary beverages linked to increased risk of type 2 diabetes, metabolic syndrome

2010-10-28
Boston, MA—A new study has found that regular consumption of soda and other sugar-sweetened beverages is associated with a clear and consistently greater risk of metabolic syndrome and type 2 diabetes. According to the Harvard School of Public Health (HSPH) researchers, the study provides empirical evidence that intake of sugary beverages should be limited to reduce risk of these conditions. The study appears online October 27, 2010, in the journal Diabetes Care and will appear in the November print edition. "Many previous studies have examined the relationship between ...

Surprise finding: Pancreatic cancers progress to lethal stage slowly

2010-10-28
Pancreatic cancer develops and spreads much more slowly than scientists have thought, according to new research from Johns Hopkins investigators. The finding indicates that there is a potentially broad window for diagnosis and prevention of the disease. "For the first time, we have a quantifiable estimate of the development of pancreatic cancer, and when it would be best to intervene," according to Christine Iacobuzio-Donahue, M.D., Ph.D., associate professor of pathology and oncology at Hopkins' Sol Goldman Pancreatic Cancer Research Center, "so there is potentially ...

A speed gun for the Earth's insides

2010-10-28
Researchers at the University of Bristol reveal today in the journal Nature that they have developed a seismological 'speed gun' for the inside of the Earth. Using this technique they will be able to measure the way the Earth's deep interior slowly moves around. This mantle motion is what controls the location of our continents and oceans, and where the tectonic plates collide to shake the surface we live on. For 2,900 km (1800 miles) beneath our feet, the Earth is made of the rocky mantle. Although solid, it is so hot that it can flow like putty over millions of years. ...

Research rejects green tea for breast cancer prevention

2010-10-28
Green tea does not protect against breast cancer. A study of data from approximately 54,000 women, published in BioMed Central's open access journal Breast Cancer Research, found no association between drinking green tea and breast cancer risk. Motoki Iwasaki, from the National Cancer Center, Tokyo, worked with a team of researchers to carry out the study. He said, "Although in vitro and animal-based studies have suggested that green tea may have beneficial protective effects against breast cancer, results from human studies have been inconclusive. Our large-scale, population-based ...

Forces for cancer spread: Genomic instability and evolutionary selection

2010-10-28
In new research published today, researchers uncover evolution in action in cancer cells. They show the forces of evolution in pancreatic tumours mean that not only is cancer genetically different between different patients, but each new focus of cancer spread within a patient has acquired distinct mutations. Effectively, ten different foci of cancer spread are ten different, but related, tumours. The complexity of pancreatic cancer genetics uncovered in this work helps to explain the difficulty of treating the disease but also strengthens the need for improved methods ...

60 Utahns are among landmark large-scale genome sequencing study

2010-10-28
(SALT LAKE CITY)—Just seven months after University of Utah geneticists took part in a landmark study that sequenced for the first time the genome of an entire Utah family, U of U researchers have taken part in another historic study that is the first large-scale genome sequencing project – 179 people representing three continents – and 60 Utahns played a major role in this study, too. Published Wednesday, Oct. 27, 2010, in Nature, the study demonstrates how quickly the science of genome sequencing is expanding – first from individuals, then to families, and now to large ...

'Smart drug' targets new mutation, dramatically shrinks aggressive sarcoma and lung cancer

Smart drug targets new mutation, dramatically shrinks aggressive sarcoma and lung cancer
2010-10-28
BOSTON--A new oral drug caused dramatic shrinkage of a patient's rare, aggressive form of soft-tissue cancer that was driven by an abnormally activated protein, physician-scientists from Dana-Farber Cancer Institute report in the Oct. 28 issue of the New England Journal of Medicine. A second patient who had a similar tumor that was not fueled by the mutant protein, called ALK (named for the first disease in which it was found, anaplastic lymphoma kinase), failed to respond to the drug, said the researchers, confirming the inhibitor's specificity for the abnormal protein. ...

LAST 30 PRESS RELEASES:

Deaf male mosquitoes don’t mate

Recognizing traumatic brain injury as a chronic condition fosters better care over the survivor’s lifetime

SwRI’s Dr. James Walker receives Distinguished Scientist Award from Hypervelocity Impact Society

A mother’s health problems pose a risk to her children

Ensuring a bright future for diamond electronics and sensors

The American Pediatric Society selects Dr. Maria Trent as the Recipient of the 2025 David G. Nichols Health Equity Award

The first 3D view of the formation and evolution of globular clusters

Towards a hydrogen-powered future: highly sensitive hydrogen detection system

Scanning synaptic receptors: A game-changer for understanding psychiatric disorders

High-quality nanomechanical resonators with built-in piezoelectricity

ERC Synergy Grants for 57 teams tackling major scientific challenges

Nordic research team receives €13 million to explore medieval book culture 

The origin of writing in Mesopotamia is tied to designs engraved on ancient cylinder seals

Explaining science through dance

Pioneering neuroendocrinologist's century of discovery launches major scientific tribute series

Gendered bilingualism in post-colonial Korea

Structural safety monitoring of buildings with color variations

Bio-based fibers could pose greater threat to the environment than conventional plastics

Bacteria breakthrough could accelerate mosquito control schemes

Argonne to help drive AI revolution in astronomy with new institute led by Northwestern University

Medicaid funding for addiction treatment hasn’t curbed overdose deaths

UVA co-leads $2.9 million NIH investigation into where systems may fail people with disabilities

With the help of AI, UC Berkeley researchers confirm Hollywood is getting more diverse

Weight loss interventions associated with improvements in several symptoms of PCOS

Federal government may be overpaying for veterans’ health care in Medicare Advantage plans

Researchers awarded $2.5 million grant to increase lung cancer screenings in underserved communities

New trigger proposed for record-smashing 2022 Tonga eruption

Lupus Research Alliance announces Lupus Research Highlights at ACR Convergence 2024

Satellite imagery may help protect coastal forests from climate change

The secrets of baseball's magic mud

[Press-News.org] New targeted lung cancer drug produces 'dramatic' symptom improvement
Early-stage trial shows promise against tumors driven by ALK gene alteration