Research from the Ireland Cancer Center of University Hospitals of Cleveland has found a promising, novel biomarker that may be used to predict the survival of patients with advanced lung cancer and their response to treatment. Afshin Dowlati, MD, hematologist/ oncologist at the Ireland Cancer Center, presented this study June 5 at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Dowlati found that patients with a low level of the biomarker ICAM had a better chance of survival and an increased response to chemotherapy. Dr. Dowlati analyzed data from a major national study, released at ASCO in 2005, that found the monoclonal antibody Bevacizumab (Avastin), in addition to standard therapy, was more effective than standard treatment alone for patients with advanced, non-squamous non-small cell lung cancer.

The analysis indicated that patients with low levels of ICAM (intercellular adhesion molecule -1), had a higher response rate to treatment (29% versus 13%) than patients with high ICAM levels. Patients with low ICAM levels also had a significantly better overall survival rate.

"We believe this research confirms a significant new prognostic marker in lung cancer," says Dr. Dowlati, who is also assistant professor at Case Western Reserve University School of Medicine. "Previously, it has been a challenge to identify those patients that will respond best to treatment and what their outcomes will be. This biomarker appears to serve as a much better predictor than gender, patients' overall health and sites of metastases." These findings confirm a pilot study performed three years ago at Ireland Cancer Center by Drs. Dowlati, Scot Remick and Keith McCrae, an expert in blood vessel disorders found in cancer.

Data was analyzed from a phase III study, conducted by the Eastern Cooperative Oncology Group (ECOG), which involved 878 patients nationwide who were randomized to standard chemotherapy - paclitaxel and carboplatin - with and without Bevacizumab. Patients who received Bevacizumab lived 2.5 months longer and had a 24.8% shrinkage in their tumors versus 9.4% shrinkage in patients who had chemotherapy alone. Bevacizumab is an anti-angiogenesis inhibitor designed to prevent the formation of new blood vessels to the tumor.

"This represents a major step forward in treating patients with advanced lung cancer," says Stanton Gerson, MD, Director of the Ireland Cancer Center and the Case Comprehensive Cancer Center. "This biomarker may help clinicians identify patients who are candidates for treatment and who will benefit from it. This finding is likely to be useful in other cancers as well."

Lung cancer is the second most commonly diagnosed cancer and is the leading cause of cancer-related death in both men and women in this country. An estimated 163,510 deaths from lung cancer occurred in 2005 in the United States, accounting for about 29 percent of all cancer-related deaths in the nation.

Other significant presentations at ASCO by Ireland Cancer Center physicians include:

-- Scot Remick, MD, presented an update to a Phase II clinical trial evaluating Ca4P (combretastatin) as a treatment for advanced anaplastic thyroid cancer. Ireland researchers found that 29% of patients experienced stability of their aggressive cancer with this anti-angiogenesis inhibitor. "Without a doubt, we have observed patient benefit from Combretastain therapy in anaplastic thyroid cancer, which is one of the most aggressive types of cancer," says Dr. Remick, Associate Director for Clinical Research at Ireland and Professor of Medicine at Case. "In some cases, patient response has been extraordinary, and supportive of the complete response observed in one patient who is still cancer free today--more than six years after participating in our initial Phase I clinical trial. We believe that the data presented today provides further evidence of the biological activity of this compound and that additional clinical trials are warranted to investigate the potential clinical benefit of combining Combretastatin with other therapies, including chemotherapy."

-- Janice Lyons, MD, on behalf of the breast cancer team of the Ireland Cancer Center, presented findings that the use of traditional chemotherapy, docetaxel, with bevacizumab (Avastin) is well tolerated in patients with locally advanced breast cancer. This Phase II study analyzed docetaxel alone compared with its use in combination with bevacizumab and found no significant differences in side effects between the two groups.

-- Panos Savvides, MD, on behalf of the head and neck cancer team of the Ireland Cancer Center, presented findings from a Phase I study of the use of Tarceva in combination with docetaxel in successfully treating advanced head and neck cancers. This promising research will be followed up by a Phase II study into the efficacy of Tarceva, an EGFR tyrosine kinase inhibitor.

-- Along with colleagues at the University of Nairobi and the Uganda Cancer Institute, Dr. Remick presented findings that oral chemotherapy is effective in the treatment of AIDS-related non-Hodgkin's lymphoma in East Africa. In a resource-limited setting where the use of intravenous treatment is challenging, the use of oral medications has comparable outcomes to its use in the United States.

Alicia Reale
alicia.realeuhhs
University Hospitals of Cleveland
uhhs/

View drug information on Avastin; Tarceva.