A new drug target in lung cancer

Lung cancer patients whose tumors over-express a cell surface molecule called CXCR4 do significantly worse than those who do not, Canadian researchers have found. Their work, reported at the 2nd European Lung Cancer Conference in Geneva, highlights the exciting possibility that the molecule could soon become a new target for personalized cancer therapy.

CXCR4 is a receptor that is found on the surface of many different cell types in the body. It plays a role in immune system signaling between cells.

In cancer, evidence that CXCR4 is involved in the growth of tumors and their spreading throughout the body (metastasis) has been growing in recent years. For example, researchers have shown in studies in mice that blocking the action of CXCR4 inhibits metastasis. But its precise role in determining outcome and metastatic tendency, especially in lung cancer, is incompletely investigated.

Dr Gwyn Bebb and colleagues from the Tom Baker Cancer Centre in Calgary, Canada set out to explore whether patients whose tumors expressed high levels of the receptor had a worse prognosis than other lung cancer patients.

They studied tumor samples from 103 patients from the Glans-Look lung cancer database who were diagnosed with stage IV non-small-cell lung cancer (cancer which had already spread to other parts of the body) between 2003 and 2006. They found that 10.7% of the tumors over-expressed CXCR4. Those over-expressers had a significantly worse clinical outcome, with a median overall survival of 2.7 months, compared to 6.1 months among low-expressers.

If confirmed in an expanded series of 170 patients from the Glans-Look database, these results will suggest that new strategies to block CXCR4 should be tested in patients whose cancers over-express the molecule, the researchers say.

"I am quite excited about the possibility of using CXCR4 as a therapeutic target, but we need to learn more about its role in each specific malignancy," Dr Bebb said.

This possibility is especially promising because CXCR4 has been well studied in the context of HIV, where it is known to be a portal for the virus's entry into immune system cells. Drugs that block CXCR4 have already been developed for HIV/AIDS patients, and Dr Bebb's group thinks these drugs could quickly and easily be tested in the cancer setting.

"This is an exciting possibility," Dr Bebb said. "It seems very likely that a better understanding of the role of CXCR4 in lung cancer will lead to new treatment strategies and might allow us to meaningfully improve treatment for some lung cancer patients in the very near future."

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New Drug May Offer Hope to Some With Lung Cancer

Maintenance therapy with the drug pemetrexed improves the survival of people with non-small-cell lung cancer whose disease has not progressed after chemotherapy, a new study has found.

Nearly 90 percent of all people who die from lung cancer have non-small-cell tumors. At the time the cancer is discovered, it's considered advanced about 40 percent of the time, according to background information in a news release from The Lancet, which is publishing the study. Chemotherapy reduces the tumors in just 40 percent of advanced cases, it said.
The phase 3 study included 663 people in 20 countries who had an advanced stage of the cancer but no disease progression after four cycles of platinum-based chemotherapy. They were randomly selected to be given pemetrexed or a placebo in 21-day cycles.

The cancers did not progress for 4.3 months, on average, in people in the pemetrexed group, compared with 2.6 months in the placebo group, the study found. People given pemetrexed survived an average of 13.4 months, compared with 10.6 months for those given the placebo.

That means that those in the pemetrexed group had a 50 percent reduction in the risk for disease progression or death and a 21 percent reduction in the risk of death only, the researchers said.

Drug-related toxic effects caused discontinuation of treatment in 5 percent of the pemetrexed group and 4 percent of the placebo group. No deaths were found to be related to pemetrexed, according to the study.

"Pemetrexed maintenance therapy is well tolerated and offers significantly improved progression-free and overall survival compared with placebo, making it a new treatment option for patients with advanced non-squamous, non-small-cell lung cancer who do not progress after initial induction therapy," Dr. Chandra Belani, of the Penn State Hershey Cancer Institute, and her colleagues concluded.

The study, which appears online and in an upcoming print issue of The Lancet, was released Sept. 19 to coincide with the European Cancer Organization meeting.

Dr. Thomas Stinchcombe of the Lineberger Comprehensive Cancer Center at the University of North Carolina, and Dr. Howard West, of the Swedish Cancer Institute in Seattle, wrote in an accompanying editorial that the use of pemetrexed as maintenance therapy "merits being considered as a strong option, reflected by the recent approval of pemetrexed in this setting by the European Medicines Agency and the U.S. Food and Drug Administration."

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AVEO's Tivozanib Demonstrates Anti-Tumor Activity in Engineered Lung Tumors Exhibiting Treatment Resistant Mutations

AVEO Pharmaceuticals, Inc., a biopharmaceutical company leveraging breakthrough discoveries in cancer biology to discover, develop and commercialize targeted oncology therapies, today announced data which demonstrates that tivozanib (AV-951) – the company's oral, triple VEGF receptor inhibitor – exhibits potent anti-angiogenic and anti-tumor activity in AVEO's proprietary in vivo lung cancer models.

Specifically, treatment with tivozanib resulted in complete tumor growth inhibition or tumor regression (shrinkage) in lung tumors driven by EGFR or KRAS mutations, which are especially difficult to treat. These data are being presented today at the 13th World Conference on Lung Cancer (WCLC) in San Francisco, abstract number PD10.1.5.

"Non-small cell lung cancer is a highly heterogeneous disease and one of the most difficult cancers to treat. Common genetic alterations responsible for the disease, such as those driven by KRAS or certain EGFR mutations, typically render anticancer treatments powerless,” stated Murray O. Robinson, Ph.D., senior vice president, oncology at AVEO. “Utilizing our proprietary cancer biology platform, we have created and treated genetically-engineered lung cancer mouse models driven by treatment resistant EGFR or KRAS, resulting in a much more realistic, human-like environment in which we can evaluate tivozanib efficacy. We are very pleased with and encouraged by the robust activity demonstrated by tivozanib in these difficult-to-treat tumor alleles."

Tivozanib is a novel, oral triple VEGF receptor inhibitor which recently completed a Phase 2 clinical study and is expected to enter a Phase 3 clinical trial later this year in patients with advanced kidney cancer. Tivozanib is being studied in several ongoing Phase 1b/2a clinical trials. Clinical results to date suggest tivozanib is a potent, well tolerated anticancer agent with broad potential as a treatment for solid tumors.

"Our innovative, proprietary cancer biology platform helps us create more relevant models of cancer in which we can evaluate the efficacy of our drug candidates preclinically, thereby increasing the probability of success in the clinic,” stated Tuan Ha-Ngoc, president and chief executive officer of AVEO Pharmaceuticals. “The robust anti-angiogenic and anti-tumor activity of tivozanib in AVEO-engineered models of TKI-resistant lung tumors, paired with the early results observed with tivozanib in patients with lung cancer from the previously reported Phase 1 trial, highlights the potential role of tivozanib in the treatment of this difficult-to-treat cancer.”

In this study, AVEO developed genetically engineered lung adenocarcinoma models driven by either treatment resistant EGFRT790M or KRAS mutant proteins by creating chimeric mice incorporating genetically modified ES cells. Tumors driven by EGFR or KRAS were propagated in vivo, to examine tivozanib activity in both subcutaneous and orthotopic settings. Treatment of subcutaneous lung KRAS tumors with tivozanib 2mg/kg and 5mg/kg daily PO for two weeks resulted in complete tumor growth inhibition and 44 percent tumor regressions respectively. Lung EGFR tumors were tested in an orthotopic setting by intravenous seeding. Tivozanib treatment was initiated after tumor establishment was detected by in vivo imaging; 5 mg/kg daily dosing for more than 10 days resulted in prolonged survival. Histologic analysis showed the same dramatic anti-angiogenic changes as in the subcutaneous KRAS tumors, indicating that tivozanib is effective in killing orthotopic lung tumors that are resistant to EGFR targeted kinase inhibitors (TKIs).

In a previously reported Phase 1 dose-escalation study evaluating tivozanib in 41 patients with advanced solid tumors clinical benefit (i.e., partial response or stable disease lasting for three months or longer) was achieved across multiple tumor types, including in those patients with lung cancer. Overall, tumor shrinkage was observed in 33 percent of all patients during treatment with tivozanib. A Phase 1b/2a trial evaluating tivozanib as monotherapy in patients with non-small cell lung cancer was initiated in March 2009 and is ongoing.

In May 2009, researchers presented complete Phase 2 data evaluating tivozanib in metastatic renal cell carcinoma (mRCC) at the 45th Annual Meeting of the American Society for Clinical Oncology (ASCO), which demonstrated prolonged progression-free survival of 11.8 months and an excellent safety profile in patients treated with tivozanib. The company expects to initiate a Phase 3 trial of tivozanib in advanced kidney cancer later this year.

Source : www.drugs.com

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What Are The Early Warning Signs Of Lung Cancer?

What is Lung Cancer?

Lung cancer is almost always caused by cigarette smoking. Many times it’s not diagnosed until the later stages of the disease which normally means that it has already spread to other tissue and organs. It’s also the leading cause of cancer deaths in the US in both men and women which is sad as the risks of developing it significantly decrease if a person does not smoke.

What are the early warning signs?

Lung cancer has many symptoms however some of the earliest signs can be mistaken for common everyday illnesses. Many of the symptoms of lung cancer do not show up until the cancer is in a later stage. Some of the early warning signs can include:

• Persistent Cough

• Recurrent Bronchitis or Pneumonia

• Loss of Appetite, Weight Loss

• Chest Pain

Some of the additional symptoms of Lung Cancer are listed below. While having any of these symptoms does not mean you have cancer, a Dr. should be consulted if you are suffering from any of the following:

• Fever without a known reason

• Abnormal Chest X-ray

• Coughing Up Blood

• Hoarseness

• Chronic Shortness of Breath

If you are suffering from any or several of these symptoms and you are a current or former smoker, you should contact your physician and schedule an appointment to have an examination. There are tests that can be done to determine the cause of your symptoms and these tests can either diagnose or rule out lung cancer. Some of the tests available include a blood count test, X-ray as well as bone scan or sputum exam.

Conclusion

If you are a smoker and are concerned about any of the symptoms you are experiencing remember the sooner you are diagnosed the better. Cancer can spread very rapidly and by beginning treatments as soon as possible you can improve your chance of survival. They say a picture is worth a thousand words. To see for yourself the harsh reality of what cancer can do, please visit: Pictures of Lung Cancer as soon as possible. These images will show you why it’s so important to stop smoking as soon as possible. http://stopsmokingonlinetoday.com is a website that's dedicated in helping people quit smoking.

by : Tim Rock

Source : www.amazines.com

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Lilly drug helps lung cancer patients live longer

The use of Eli Lilly and Co's Alimta following successful chemotherapy treatment helped patients with advanced lung cancer live significantly longer, according to data released on Saturday.

The study, presented at the American Society of Clinical Oncology (ASCO) meeting in Orlando, Florida, also confirmed that the benefit from Alimta is primarily limited to the more common nonsquamous type of non-small cell lung cancer.

Patients in the study with that type of cancer who were treated with Alimta as a so-called maintenance therapy lived more than five months longer than those who got a placebo.

"This should become the standard of care," Dr. Chandra Belani, deputy director of the Penn State Cancer Institute and the study's lead investigator, said in an interview.

"This is the first time that there is a benefit of five months in nonsquamous patients. As the cumulative toxicity is minimal it can be given for a prolonged duration of time," Belani said.

Alimta, known chemically as pemetrexed, is approved for use in combination with chemotherapy as an initial treatment for advanced nonsquamous non-small cell lung cancer. Approval as a maintenance therapy -- to delay worsening of the disease after chemotherapy has stalled tumor growth -- would add a lucrative new revenue source for the medicine.

Alimta had sales of $1.15 billion in 2008.

"This is the next step in the overall management (of the disease)," Belani said.

"If you can give it for a prolonged duration of time you then can change the acute nature of the disease to a chronic disease. That's the intent, that you can maintain that state of response with the initial chemotherapy," Belani explained.

Preliminary results from the 663-patient, late-stage study presented at last year's ASCO meeting demonstrated Alimta's ability to delay disease progression when used as a maintenance therapy. The latest data for the first time showed a significant improvement in overall survival, researchers said.

Overall survival -- the extension of a patient's life -- is considered the gold standard by physicians and by health regulators making approval decisions.

All patients in the study had advanced or metastatic non-small cell lung cancer that had not progressed after four cycles of platinum-based chemotherapy.

In the overall patient population, those who received Alimta lived for an average of 13.4 months versus 10.6 months for patients in the placebo group. Among patients with the nonsquamous type of cancer, those who got Alimta lived an average of 15.5 months compared with 10.3 months in the placebo group. Both results were considered to be statistically significant, Belani said.

The lack of benefit among patients with the squamous subtype confirmed what had been seen in prior Alimta studies.

Side effects more common in the Alimta group were fatigue and low white blood cell counts, researchers said. There were no drug-related deaths in the study.

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