Sandy Hutchens Cancer Prevention

An experimental cancer drug recently acquired by Onyx Pharmaceuticals Inc (ONXX.O) showed promising response rates in patients with relapsed and/or refractory multiple myeloma, according to interim data from a pair of small mid-stage trials.

The studies, presented on Monday at the American Society of Hematology (ASH) meeting in New Orleans, tested carfilzomib given intravenously every 28 days in 73 patients who had not previously been treated with Takeda Pharmaceuticals’ (4502.T) Velcade, and in 33 others following treatment with Velcade.

“These interim results suggest that carfilzomib could benefit patients with multiple myeloma who are no longer responding to current therapies,” Dr. David Siegel, co-investigator of the studies, said in a statement.

Onyx acquired carfilzomib with its purchase last month of Proteolix Inc, saying the drug for multiple myeloma, a blood cancer, has the potential for accelerated U.S. approval in 2011.

Among those who had not received prior Velcade treatment, or Velcade naive patients, carfilzomib led to an overall response rate (ORR) of 46 percent among 54 patients at a 20 milligram dose, and a 53 percent overall response among 19 patients with dose escalation to 27 mg, researchers said.

Patients who were previously treated with Velcade, known chemically as bortezomib, achieved an overall response rate of 18 percent when administered carfilzomib, researchers said.

The Velcade naive patients had relapsed or worsened following other prior therapies.

“While we do not yet model carfilzomib revenue, we do think this agent has real potential for accelerated approval and to establish a meaningful position in the multiple myeloma market based on strong activity and promising side effect profile,” Robert W Baird analyst Chris Raymond said in a research note.

Multiple myeloma results from abnormal plasma cells, usually in the bone marrow. More than 180,000 people are living with the disease worldwide and about 86,000 new cases are diagnosed annually, Onyx said.

Median survival from relapsed and refractory multiple myeloma — when the disease returns and progresses following a response to therapy — can be as short as six to nine months.

In addition to overall response, the Proteolix-sponsored trials looked at secondary goals of time-to-progression and duration of response.

In the Velcade naive group time-to-progression, or the amount of time before the disease worsens, was 7.6 months, and duration of response was 8.4 months.

In the group previously treated with Velcade, interim results showed a time-to-progression of 5.3 months and duration of response of more than 9 months.

“These findings are truly an advance for patients with multiple myeloma,” Dr. Michael Wang, of the MD Anderson Cancer Center in Houston and one of the lead investigators, said.

Noting that other life-extending drugs often have adverse side effects, including severe nerve pain, Wang said “carfilzomib is showing good response rates with an improved side effects profile.”

Treatment with carfilzomib was well tolerated with no unexpected side effects, researchers said.

More than 20 percent of patients were able to complete the full 12 cycles (48 weeks) of therapy in both studies without cumulative side effects, and with low incidence of neuropathy, researchers said.

“These data support our ongoing carfilzomib program in multiple myeloma, a disease that has poor long-term survival,” Michael Kauffman, Onyx’s interim chief medical officer, said in a statement, adding that the company could file its application seeking U.S. approval by the end of 2010.

Onyx shares were off 18 cents or 0.6 percent at $29.59 on the Nasdaq at midday.

Histopathology Bone–Multiple myeloma

Gary Howell is a cancer survivor. He participated in the Breast Cancer Fund’s 2009 Climb Against the Odds trek up Mt. Shasta in California. Hutchens Cancer Prevention feels that this article by Mr. Howell is so important in spreading information about the need to focus on prevention that we quoted it in its entirety.

The month of October is Breast Cancer Awareness month. There have been numerous articles, events, fundraisers and television programs oriented toward this theme and many of them feature the term “cure” prominently in the title.

Certainly a cure for breast cancer would be a welcome occasion, but this focus unfortunately can mask the many avenues of breast cancer prevention that are already documented; many are already available to women and some need additional research and/or legislation.

Between 1973 and 1998, the incidence of breast cancer in the U.S. increased by more than 40 percent. In 2008, an estimated 250,000 U.S. women were diagnosed with breast cancer and 40,500 died of the disease.

Clearly something is happening to cause this increase. Women need to be informed about risk factors that have developed during this 25-year period and we all need to work together to eliminate them. I would like to emphasize this point by illustrating it with a very personal example.

My wife, Nancy, reached menopause at the relatively early age of 42 and experienced the array of annoying symptoms that often characterize this event; hot flashes and moodiness being the most acute. Like so many women, she embarked on a regimen of hormone replacement therapy, or HRT, and the symptoms disappeared.

Nancy’s mother began menopause at that same age and took HRT for 34 years without event. Being her mother’s daughter, she followed her footsteps. There is no history of breast cancer in her family; but in the United States, where a woman’s lifetime risk of developing breast cancer is an alarming 1 in 8, no more than 1 in 10 women with breast cancer has a genetic history of the disease!

Nancy is one of the fortunate women whose routine mammogram screening revealed the cancer in its earliest stage before a palpable lump had developed and before the cancer spread to the lymph system. Following a regimen of chemotherapy and radiation, the odds are very good that Nancy’s cancer will not return.

I can assure you, however, that Nancy would have gladly disabused herself of the benefits of HRT in favor of avoiding the exhausting and painful treatments that were prescribed.

An estimated 80,000 synthetic chemicals have been registered for use in the United States in the last 40 years, but fewer than 10 percent of them have been fully tested for their effects on human health. Scientific evidence links toxic chemicals and radiation in our every day environment to the high rates of breast cancer. Some of this exposure is from seemingly benign sources such as cosmetics, beauty creams, sunscreen lotions, plastics and foodstuffs containing artificial hormones and additives.

We must:

* Educate ourselves and our loved ones about risky behaviors.

Some suggested links on the internet are:

http://www.breastcancerfund.org

http://www.safecosmetics.org

http://www.healthandenvironment.org

* Become involved in the legislative process. Three suggested links are:

Massachusetts Breast Cancer Coalition, http://www.1in8@mbcc.org

National Women’s Health Network, http://www.womenshealthnetwork.org

Jane Cusumono Foundation, http://chateauwallyfilms.com/breastcancerresources.htm

This month, when you notice pink ribbons in the grocery and department stores, and football players, golfers and politicians wearing pink, keep in mind that we not only need a cure for breast cancer, but remember also that prevention is so much easier than treating this devastating disease.

Is Prevention the Cure for Cancer?

The Translational Genomics Research Institute and Scottsdale Healthcare have discovered lung cancer ‘pathways’ that could become targets for new drugs, according to a scientific paper published online today by the Journal of Thoracic Oncology.

Dr. Glen Weiss, Director of Thoracic Oncology at TGen Clinical Research Services (TCRS) at Scottsdale Healthcare, said the study showed the value of conducting computer modeling, or “in silico” research.

TCRS is a partnership of TGen and Scottsdale Healthcare. The partnership allows molecular and genomic discoveries made by TGen and others around the world to reach the patient bedside in the Virginia G. Piper Cancer Center at Scottsdale Healthcare as quickly as possible through clinical trials with agents directed at specific cancer targets.

Researchers hope that over time in silico research will help lower health care costs while speeding up the process of turning scientific discoveries into treatments for patients.

“There are pathways that you can identify just from an in silico analysis. And we can use these types of tools to explore treatments for patients, down the road,” said Dr. Weiss, an Associate Investigator in TGen’s Cancer and Cell Biology Division and the senior author of the paper, which will appear in print in JTO’s November edition.

The study sought to identify metabolic pathways — a series of chemical reactions occurring within a cell — that could be targeted by drugs in patients with both small-cell and large-cell lung cancers. Small-cell lung cancer represents about 15 percent of all lung cancers. The rest are classified as non-small cell lung cancer, of which large-cell lung cancer represents about 10 percent.

The study used publicly available data sets, searching for connections that may have been previously overlooked.

“Within those datasets, there are common pathways. We point out some examples that provide some proof-of-principle from the in silico search,” said Dr. Weiss, who was joined in his research by TGen’s Dr. Chris Kingsley and by Dr. Anoor Paripati of the Scottsdale Clinical Research Institute at Scottsdale Healthcare.

As an example, the study cites one particular signaling pathway, Wnt/ß-catenin, that could be targeted by two drugs, vorinostat and dasatinib, both of which are under study in clinical trials.

“This is an exploration of the publicly available data sets in an attempt to answer a new question. It shows that you can look at pathways and identify targets. We did our validation by looking at what’s been tested, or what’s available already,” Dr. Weiss said.

In silico research, which is far less costly than conducting genetic profiling analysis of cancer tumors, will become more common as the National Cancer Institute ramps up its cancer Biomedical Informatics Grid, also known as caBIG.

Such in silico research should lead to targets for further laboratory and clinical research, and also should help clinicians provide more personalized treatment for patients, Dr. Weiss said.

“There is going to be a wealth of profiling data out there in the near future. You can then apply techniques like this, and hopefully design smarter clinical trials to find the drugs that would work,” Dr. Weiss said.