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The Lancet Oncology

Monday, December 14, 2009

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:

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