2 new therapies show promise for cancer patients

Clinical researchers at Scottsdale Healthcare and TGen today announced the results of two clinical trials that show promise for patients battling cancer.

The Phase I clinical trial findings, presented at the this weeks Annual Meeting of the American Association for Cancer Research by Daniel Von Hoff, MD, FACG, focused on basal cell carcinoma (BCC) and pancreatic cancer. The Arizona trials were conducted at TGen's Clinical Research Service (TCRS) at Scottsdale Healthcare, a strategic alliance between TGen and Scottsdale Healthcare’s Clinical Research Institute.

Basal Cell Carcinoma

In the first trial, a novel molecule, GDC-0449, shrinks tumors in basal cell carcinoma (BCC) while having limited side effects, including a loss of sense of taste, and a small amount of hair loss and weight loss, suggesting a viable new treatment option. GDC-0449 works by blocking a pathway — a series of chemical reactions within a cell— known as Hedgehog, containing two genes (PTCH and SMO) that lead to a known tumor-promoting gene called GLI1. Alterations in any of these genes have been shown to lead to basal cell carcinoma and other diseases. GDC-0449 is a chemical synthetic designed to replicate the properties of cyclopamine, a chemical found in nature.

“Basal cell carcinoma affects about one million people a year and a proportion of these patients have disease that is not curable with surgery. We currently do not have any treatments that can effectively slow tumor growth in these advanced patients. This finding has potential importance in this population,” said Daniel D. Von Hoff, M.D., Physician in Chief at the Translational Genomics Research Institute (TGen) and Chief Medical Officer for the Scottsdale Clinical Research Institute at Scottsdale Healthcare.

Typically diagnosed with a simple biopsy, the risk of BCC increases for those individuals with a family history, or prolonged exposure to ultraviolet (or UV) rays from the sun. While BCC has an extremely low rate of metastasis, it can lead to scarring and disfigurement if left untreated.

The trial results showed durable clinical benefit —defined as tumor shrinkage visible on X-ray or other physical exam or improvement in symptoms without tumor growth— was observed in eight out of the nine patients evaluated.

The first patient treated in the trial has shown clinical improvement for approximately 450 days and is ongoing, Von Hoff says, with almost no side effects beyond minimal hair loss.

“He came to us short of breath and in pain, but he has had a very dramatic response with this drug,” Von Hoff said.

Further evaluations of the study participants measured the presence of GLI1 in skin cells sampled from the participants. Among all patients tested to date, there was reduction in this marker, indicating that the drug was affecting the hedgehog pathway.

The trial, sponsored by Genentech, also included clinical sites at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland and Karmanos Cancer Institute, Detroit, Michigan.

Pancreatic Cancer

In the second trial, Von Hoff and colleagues showed that a novel combination of two drugs (nanoparticle albumin-bound paclitaxel, or “nab-pacilitaxel” and gemcitabine) showed a significant clinical benefit in more than 80 percent of pancreatic cancer patients.

“Unfortunately, most patients with pancreatic cancer have a very poor survival, and until now, the only option has been gemcitabine alone or in combination with erlotinib,” said Von Hoff.

The researchers utilized the Target Now™ tumor profiling analysis, a cutting-edge oncology testing service performed by Caris Dx and Caris MPI, to better understand the characteristics expressed in patient’s tumors. In this ongoing research program, Von Hoff and colleagues found the SPARC (Secreted Protein Acidic and Rich in Cysteine) protein to be commonly found in pancreatic cancer specimens. The SPARC protein is being investigated by Abraxis BioScience in this trial as a potential target for nab-paclitaxel. A test for SPARC, developed at Abraxis and Caris MPI and applied by Caris MPI under contract with Abraxis, was utilized to analyze SPARC in the pancreatic cancer patients in the trial.

The finding of SPARC protein in pancreatic cancer patients, also described by other investigators, was the basis for this phase I clinical trial that Von Hoff presented at AACR.

“Chemotherapy often means combining more than one drug, and we do not want to just take the next thing off the shelf. We want to know as much about a tumor as possible going in,” Von Hoff said.

Researchers reported on the first 20 patients of what will eventually be a 42-patient trial.

“This was a phase I trial, and phase I trials are usually designed to test safety, hoping it will also determine efficacy. The fact that we saw this kind of activity in a phase I trial is dramatic,” Von Hoff said.

“The rationale behind the combination of Gemcitabine plus Abraxane was based on careful science and was designed and executed by some of the leading experts in pancreas cancer in the world. While the data is preliminary and longer follow-up will be important, the biochemical and radiographic responses look very encouraging”, says Dr. Laheru of Johns Hopkins Kimmel Cancer Center.

Source: The Translational Genomics Research Institute

Related stories:

Researchers find molecule that kills kidney cancer cells
Kidney cancer patients generally have one option for beating their disease: surgery to remove the organ.
Nanotechnology for fighting cancer
The National Cancer Institute (NCI) announced today at a media briefing a new $144.3 million, five-year initiative to develop and apply nanotechnology to cancer. Nanotechnology, the development and engineering of devices so small that they are measured on a molecular scale, has already demonstrated promising results in cancer research and treatment
Older renal cancer patients appear to benefit from sorafenib treatment
Older and younger patients with renal cancer derive similar benefit from sorafenib therapy and tolerate the drug equally well, according to a study published online October 7 in the Journal of the National Cancer Institute.
Largest review of its kind associates anti-inflammatory drugs with reduced breast cancer risk
Analysis of data from 38 studies that enrolled more than 2.7 million women – the largest of its kind – by researchers at the University of British Columbia, Vancouver Coastal Health Research Institute, and the University of Santiago de Compostela reveals that regular use of Non Steroidal Anti-Inflammatory Drugs (NSAIDs) is associated with a 12 per cent relative risk reduction in breast cancer compared to non-users.
Compassion meditation may improve physical and emotional responses to psychological stress
Data from a new study suggests that individuals who engage in compassion meditation may benefit by reductions in inflammatory and behavioral responses to stress that have been linked to depression and a number of medical illnesses. The study's findings are published online at www.sciencedirect.com and in the medical journal Psychoneuroendocrinology.
Tamoxifen chemoprevention tied to early detection of breast cancer
The drug tamoxifen does not prevent or treat estrogen receptor (ER) negative breast cancer, but it can make the disease easier to find, researchers report in the Oct. 1 Journal of the National Cancer Institute.
Anti-cancer drug prevents, reverses cardiovascular damage in mouse model of premature aging disorder
An experimental anti-cancer drug can prevent -- and even reverse -- potentially fatal cardiovascular damage in a mouse model of progeria, a rare genetic disorder that causes the most dramatic form of human premature aging, National Institutes of Health (NIH) researchers reported today.
Red wine decreases the risk of lung cancer
Moderate consumption of red wine may decrease the risk of lung cancer in men, according to a report in the October issue of Cancer Epidemiology, Biomarkers & Prevention¸ a journal of the American Association for Cancer Research.

News discussion:

Medicine & Health news