South Nassau Communities Hospital

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South Nassau in the Community

08/07/2008

Lung Cancer Studies Earn Prestigious Award


Shahriyour Andaz, MD, FACS, FRCS, Director of Thoracic Oncology at South Nassau Communities Hospital, is the co-author of two studies that earned honors at the Brooklyn and Long Island Chapter of the American College of Surgeons Murry Friedman Surgical Resident Competition.

The award-winning studies focused on using gene amplification to determine chemotherapy resistance in early stage lung cancer and patterns of cross-resistance in early stage lung cancer that has been surgically treated.

In the study, Can Gene Amplification of 1q25 Predict Taxane (Taxol) Resistance in Early Lung Cancer, Dr. Andaz and co-authors Dr. Diya Tantavi; Dr. Svetlana Danovich; Dr. Mary Kate Plantholt; and Dr. Stewart Fox, FACS, concluded that Taxol is less effective when gene amplification is present in Chromosome 1q25. Taxol is a chemotherapy drug classified as a "taxane," which is a drug that blocks cell growth by stopping cell division. Gene amplification is associated with aggressive tumors, metastatic cancer, and chemotherapy resistance and hinders cancer remission and the length of remaining disease-free.

Taxol is recognized for its success in treating lung and a variety of other malignancies, including breast and ovarian. Despite preclinical and clinical success of cancer drugs, tumors have the ability to develop an acquired resistance to them, which is a major obstacle to treating and curing cancer.

To reach their conclusion, Dr. Andaz and the research team stained 40 lung tumors with Chromosome 1q25 then screened the tumors to find amplified regions. Overall, 10 of the specimens presented with 1q25 amplification in three or more gene copies and proved to be resistant to Taxol based on the Extreme Drug Resistant (EDR) Assay.

The EDR Assay was developed for testing in vitro (in an artificial environment outside the living organism) drug responses in solid tumors, and is the only solid tumor assay capable of identifying extreme drug resistance with over 99% accuracy. Validation of the EDR Assay has been documented by 450 clinical correlations obtained over an eight year period. Results of this study were published in the Journal of the National Cancer Institute. Subsequent studies have demonstrated a direct relationship between EDR Assay results and patient survival. Results from the EDR Assay are used to determine the probability of non-response (or extreme drug resistance) by a tumor to the selected chemotherapy.

“The findings are critical to enhancing survival in lung cancer patients,” said Dr. Andaz. “Additionally, the more concrete our understanding is of the mechanisms of cancer drug resistance, the more precise will our strategies be for cancer treatment.”

The study on patterns of cross resistance examined 82 non-small cell lung cancer specimens for their EDR to the cancer drug Cisplatinum. Entitled Patterns of Cross-resistance in Surgically Resected Lung Cancer – Enhancing Platinum Based Adjuvant Therapy Protocols, the study produced “compelling evidence” to warrant “careful evaluation” of the chemotherapy drugs that will be used after surgery for early stage lung cancer.

Chemotherapy is given to patients after lung cancer surgery to increase survival. Currently, most oncologists use a platinum-based chemotherapy and the results have been a minimal 5% increase in survival over 5 years. (Platinum-based chemotherapy, also known as heavy metal alkylating-like agents, has been used to treat cancer for more than 30 years. The therapy interferes with the genetic material (DNA) inside the cancer cells and prevents them from further dividing and growing more cancer cells.)

Dr. Andaz and co-authors Dr. Christakis Markella, MS, PH, Dr. Svetlana Danovich, Dr. Plantholt, and Dr. Fox cross-treated the specimens that showed resistance to Cisplatinum with five additional cancer drugs. The specimens were exposed to each drug in excess of the maximum allowable dosage for five consecutive days in a highly controlled environment. This approach resulted in tumor exposure to each drug between five to 80 times greater than the typical exposure. If malignant cells are manufactured under such extreme chemotherapeutic exposure conditions, then the typical treatment will be ineffective with a probability greater than 99-percent.

Of the 82 specimens, 13 presented EDR to Cisplatinum. Of those 13, 5 were EDR to Gemcitabine; 4 were EDR to Taxol; 4 were EDR to Toptecan; 2 were EDR to Navelbine; and 2 were EDR to Etopside.

“The results of this study will help oncologists identify the second drug that will be most effective in treating a tumor that has shown to be EDR to Cisplatinum or a Cisplatinum-based chemotherapy,” said Dr. Andaz, “thereby, increasing the rate of survival after non-small cell lung cancer surgery.”

Dr. Andaz specializes in complex chest cancer procedures and minimally invasive thorascopic surgery. His expertise includes chest wall sarcomas resection and reconstruction, mesothelioma, tracheal resections and reconstructions, endobronchial surgery, esophageal resection and lung volume reduction surgery. Eliminating the need for large incisions and painful rib resections, the minimally invasive approach offers faster healing and shortened recovery time. For more information or to schedule an appointment with Dr. Andaz, call 1-877-SouthNassau, or visit southnassau.org.



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