New Drug Targeting Advanced Thymic Cancer May Bring Hope to Patients

The Translational Genomics Research Institute (TGen), a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking medical research in oncology, neurological disorders and diabetes, and Scottsdale Healthcare are testing a new drug specifically for thymic cancer. The new drug candidate is designed to stop abnormal cell division and duplication, a common feature of cancer.


The thymus, a small organ that lies in the upper chest under the breastbone or sternum. As a part of the lymph system, the thymus makes lymphocytes that protect the body against infections.
There are different types of tumors of the thymus. Both thymomas (or Thymic epithelial tumors) with clearcut cytologic features of malignancy and thymic carcinomas are rare tumors of the cells that are on the outside surface of the thymus. The tumor cells in a thymoma look similar to the normal cells of the thymus, grow slowly, and rarely spread beyond the thymus. On the other hand, the tumor cells in a thymic carcinoma look very different from the normal cells of the thymus, grow more quickly, and have usually spread to other parts of the body when the cancer is found. Thymic carcinoma is more difficult to treat than thymoma.

At the time of diagnosis, thymic carcinoma has usually metastasized. This can make formulating a treatment plan more challenging. Surgical removal of the tumor is usually the first line of therapy. Depending on the stage of the cancer at diagnosis, chemotherapy, hormone therapy, and radiation may also be prescribed. The 10-year survival rate for patients diagnosed with thymic carcinoma is approximately 28%.

Thymic carcinoma often goes unnoticed until the tumor begins to press on the patient's windpipe. It can also produce hormones that frequently cause symptoms. These may include a persistent cough, asthma, swelling of the face, diarrhea, red and warm skin, and chest pain. Some patients may have no symptoms of the cancer at all. In these cases, the tumor may have been an incidental finding on a routine chest x-ray.

Preliminary results of PHA-848125AC, a TRK A antagonist pro, is uced by Nerviano Medical Sciences of Milan, Italy’s largest pharmaceutical research and development facility, showed favorable results in treating the disease.

“From the initial trial in patients with advanced cancers, this drug is well tolerated. We are now focusing on thymic cancer based on our initial results, to hopefully find a treatment that is successful for this rare cancer - where there is no standard approved treatment,” said Dr. Glen J. Weiss, principal investigator for this trial and Director of Thoracic Oncology at TGen Clinical Research Services (TCRS) at Scottsdale Healthcare.

TCRS is a partnership between TGen and Scottsdale Healthcare that enables laboratory discoveries to be quickly turned into targeted therapies that can be tested with patients at the Virginia G. Piper Cancer Center in Scottsdale.

This Phase II clinical trial of as many as 60 adults with advanced thymic cancer will help determine if PHA-848125AC is an active drug for this disease. The thymus is a small organ near the lungs and heart that is a key part of the body’s immune system during fetal and childhood development.

Dr. Jeffrey Isaacs of Southwest Hematology Oncology in Phoenix, has seen first-hand how this agent made a difference for patients with thymic cancer. He said he is enthusiastic about a drug specifically targeting this rare cancer population to hopefully improve their outcomes.

PHA-848125AC will be administered orally. The study will be open at Scottsdale Healthcare, the Institute Gustave Roussy and the Hopital Larrey in France and at the University of Turin, San Luigi Hospital in Italy.

The intent of the study is to assess the antitumor activity of PHA-848125AC as second-line treatment in patients with recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy. Patients will receive 150 mg/day once daily, for 7 consecutive days (days 1 to 7) followed by 7 days of rest (days 8 to 14) in a 2-week cycle until disease progression or unacceptable toxicity will develop.

For more information about current clinical trials:

• Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma

Also read

• Johnson S B et al. Thymoma: Update for the new millennium. The Oncologist. Vol. 6, No 3, 239- 246, June 2001.
• Lara, Jr P N (2000) Malignant thymoma: current status and future directions. Cancer Treatment Reviews April 2000; 26: 2 127-131.
• Detterbeck FC, Parsons A M Thymic Tumours. The Annals of Thoracic Surgery 2004; 77:1860- 9.
• Eng T et al (2003) Thymic carcinoma: state of the art review. International Journal of Radiation Oncology Biology Physics. Vol 59 No 3.
• Giaccone G Treatment of malignant thymoma. Current Opinion in Oncology 2005 17: 140- 146.
• World Health Organisation classification of tumours. Pathology and genetics. Tumours of the lung, pleura, thymus and heart. World Health Organisation Classification of Tumours Vol.10 Eds. Travis WD et al. WHO Press, 2004.
• Textbook of Uncommon Cancer (3rd edition) Eds. Raghavan et al. Wiley, 2006.

See PubMed abstracts:

• Nakagawara A Trk receptor tyrosine kinases: a bridge between cancer and neural development Cancer Lett.2001 Aug 28;169(2):107-14.
• Mitsutake N, Yamashita S The role of cancer genes in thyroid cancer and molecular targeted therapy Nippon Naika Gakkai Zasshi. 2009 Aug 10;98(8):1999-2005.

Overweight and Obesity Causes over 124,000 New Cancers a Year in Europe

According to estimates from a new modeling study, at least 124,000 new cancers in 2008 in Europe may have been caused by excess body weight. The proportion of cases of new cancers attributable to a body mass index of 25kg/m2 or more were highest among women and in central European countries such as the Czech Republic, Latvia, Slovenia and Bulgaria.

The lead author of a study called ‘Incident cancer burden attributable to excess body mass index in 30 European countries’, published in the International Journal of Cancer, Dr Andrew Renehan, told oncologists and other medical professionals gather together in Berlin, Germany during the combined 15th congress of the European CanCer Organisation and the 34th congress of the European Society for Medical Oncology: “As more people stop smoking and fewer women take hormone replacement therapy, it is possible that obesity may become the biggest attributable cause of cancer in women within the next decade.”

Dr Renehan, who is a senior lecturer in cancer studies and surgery at the University of Manchester (UK), and his colleagues in the UK, The Netherlands and Switzerland, created a sophisticated model to estimate the proportion of cancers that could be attributed to excess body weight in 30 European countries. Using data from a number of sources including the World Health Organization and the International Agency for Research on Cancer, they estimated that in 2002 (the most recent year for which there are reliable statistics on cancer incidence in Europe) there had been over 70,000 new cases of cancer attributable to excess BMI out of a total of nearly 2.2 million new diagnoses across the 30 European countries.

The percentage of obesity-related cancers varied widely between countries, from 2.1% in women and 2.4% in men in Denmark, to 8.2% in women and 3.5% in men in the Czech Republic. In Germany it was 4.8% in women and 3.3% in men, and in the UK it was 4% in women and 3.4% in men.

Then, the researchers projected the figures forward to 2008, taking into account what was known about shifts in the distribution of BMI, the dramatic decline in women’s use of hormone replacement therapy (HRT) from 2002 onwards following research that showed it increased the risk of breast cancer, and the wider use of PSA screening for prostate cancer in men.

They found that the number of cancers that could be attributed to excess body weight increased to 124,050 in 2008. In men, 3.2% of new cancers could be attributed to being overweight or obese and in women it was 8.6%. The largest number of obesity-related new cancers was for endometrial cancer (33,421), post-menopausal breast cancer (27,770) and colorectal cancer (23,730). These three accounted for 65% of all cancers attributable to excess BMI.

“I must emphasize that we are trying not to be sensationalist about this,” said Dr Renehan. “These are very conservative estimates, and it’s quite likely that the numbers are, in fact, higher.”

The number of new cases of obesity-related esophageal cancer was particularly high in the UK relative to the rest of Europe. “This country accounts for 54% of new cases across all 30 countries,” said Dr Renehan. “This may be due to synergistic interactions between smoking, alcohol, excess body weight and acid reflux – and is currently an area where research is required.”

Until 2002 when HRT use dropped dramatically following the results of the Women’s Health Initiative Trial (USA) that showed an increased risk of breast cancer in women taking HRT, Dr Renehan said that HRT masked and diluted the effects of obesity on the incidence of breast cancer. “In women who used HRT it wasn’t clear what proportions of breast cancers were caused by HRT or by obesity. In women who don’t take HRT, the effect of obesity was much clearer. Now that far fewer women are using HRT, it is much easier to see the effect of obesity on the incidence of breast cancer, and also on endometrial cancer. Consequently, the proportions of these cancers attributable to obesity have increased.”

Dr Renehan said that although European countries were taking steps to tackle the obesity epidemic, this study underlined the urgency of the task and the scale of the problems caused by increasingly overweight populations.

“The overall size of the burden of increasing cancer incidence should inform health policy. For example, it is clear that, in both relative and absolute terms, obesity-related cancer is a greater problem for women than for men. At a country level, it is a greater problem for central European countries like the Czech Republic, whereas it is less of a problem in France and Denmark. Similarly, obesity-related esophageal cancer seems to be a substantial and unique problem in the UK.

“The study also identifies priorities for research into certain cancers, namely endometrial, breast and colorectal cancers. In the face of an unabating obesity epidemic, and apparent failure of public health policies to control weight gain, there is a need to look at alternative strategies, including pharmacological approaches.”

Dr Renehan’s own research is trying to relate these epidemiological findings back to the biological mechanisms that are at work. His research uses the observed interactions between excess BMI and cancer risk to guide questions in the laboratory.

For more information:

• ECCO15 – ESMO 34 Abstract no: 327, Oncopolicy session: Drug and lifestyle mediated prevention initiatives in Europe. Thursday 11.15-12.15 hrs CEST (Hall 3)

European specialists are joining forces to improve lung cancer treatment

Prevention, personalized therapies and closer collaborations between surgeons, medical oncologists and radiation oncologists will result in better outcomes for lung cancer patients and those at risk, a leading European expert says.

“Lung cancer is a complex disease. It is one of the most complex cancers, and the more we learn about the biology of the disease, the more we realize that improved cancer care will result from multidisciplinary treatment,” said Prof Robert Pirker, from the Medical University of Vienna, Austria (Spitalgasse 231090 Wien 9., Alsergrund, Wien, Austria). Prof Pirker is co-chair of the scientific committee of a new medical conference, the European Multidisciplinary Conference in Thoracic Oncology (EMCTO), being held for the first time this year, 1-3 May, at the Palazzo dei Congressi in Lugano, Switzerland.

The conference aims to further clinical and scientific cooperation between disciplines to help in the fight against lung cancer. Designed as a regular multidisciplinary, educational meeting, the organizers feel that the meeting may help strengthening general knowledge and providing an updated overview of prevention, screening, diagnosis, treatment modalities and results of translational research. One of the goals of the organizers is to facilitate interaction between the specialties in order to promote an integrated approach to diagnosis and treatment of chest tumors and to strengthen European cooperation and scientific exchange in multidisciplinary management of lung cancer.

A common cancer
Lung cancer is the most common cancer in the world. In men, the highest incidence rates are seen in Europe (especially eastern Europe) and North America. In women, high incidence rates are found in North America and in Europe, particularly in northern and western Europe.

Role of tobacco and smoking
Tobacco smoking is well established as the main cause of lung cancer and about 90% of cases are thought to be tobacco related. There is a clear dose-response relation between lung-cancer risk and the number of cigarettes smoked per day, degree of inhalation, and age at initiation of smoking. Researchers have noted that someone who has smoked all his life has a 20 -30 times greater risk of getting lung-cancer than a non-smoker. The link between tobacco-use and smoking is further emphasized by the fact that the risk of lung cancer decreases with time since smoking cessation.

Research has also shown that while the incidence of lung cancer among men in many Western European countries has been decreasing since the 1980s, the age-adjusted rate for men in other European countries increased at least until the 1990s. Among women this peak in incidence had not been reached in the 1990s. At the same time, the proportion of adenocarcinoma in both men and women has been increasing over time. The most likely explanation for this trend is the shift to low-tar filter cigarettes.

Screening Emphasized
Since the early 2000’s there has been renewed interest in screening because spiral computerized tomography (CT) can detect small asymptomatic lesions more effectively than conventional radiography. Although cure rates for such lesions are very good, there is to date no evidence for effectiveness of mass-screening strategies.

Targeted therapies
Over the past 5 years, researchers have established that for patients with operable cancer, surgery followed by chemotherapy can result in good outcomes. Now, large clinical trials are beginning to evaluate that adding molecular targeted therapies can further improve the chance of a successful outcome for some patients. In addition, doctors are now attempting to refine their treatments based on the clinical characteristics of individual patients, and based on the molecular profile of their tumor.

“More sophisticated and complex treatments require more cooperation,” Prof Pirker says. “That is one of the reasons why we have organized this conference. We believe the result will be better outcomes for lung cancer patients.”

For patients with metastatic disease, targeted therapies have already entered clinical practice or have shown survival benefit in clinical trials. Combinations of chemotherapy and radiotherapy are also improving outcomes of loco-regional non-small-cell lung cancer. “Cure is now possible in about 15% to 20% of patients whose disease can be treated in this way,” adds Prof Jean-Paul Sculier, from Institut Jules Bordet in Brussels, Belgium. (121 Boulevard de Waterloolaan, Bruxelles 1000 Brussel 121 Boulevard de Waterloolaan, Bruxelles 1000 Brussel, telephone +32 254 1311). Prof Sculier will chair a session on treating advanced disease at the conference.

During the European Multidisciplinary Conference in Thoracic Oncology Research groups will present new data that reflect these developments, including:

• A study comparing radiotherapy alone to sequential chemotherapy and radiation in locally advanced non-small-cell lung cancer, plus a correlation of gene expression level with survival (UK).
• Promising results from a study of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small-cell lung cancer (Poland).
• Confirmation that EGFR mutations (deletion in exon 19, missense L858R) are the most important predictors of sensitivity to tyrosine-kinase inhibitor targeted therapies (Italy)
  

Barbara Zolty from the World Health Organization (Avenue Appia 20 1211 Geneva 27 Switzerland telephone +4122791211) will also highlight the importance of preventing lung cancer as the first and foremost weapon against lung cancer. Ms Zolty will speak about the WHO Tobacco-Free Initiative with an enlightening keynote lecture entitled “A thousand seconds, a thousand lives.”

The EMCTO Conference is co-organized by the European Society for Medical Oncology (ESMO), the European Society for Therapeutic Radiology and Oncology (ESTRO), the European Society of Thoracic Surgeons (ESTS) and the European Respiratory Society (ERS)

For more information also read:

• Janssen-Heijnen ML and Coebergh JW, The changing epidemiology of lung cancer in Europe, Lung Cancer. 2003 Sep;41(3):245-58 )