Cancer is the second-leading cause of death in the United States, and if projections from the World Health Organization are correct about a nearly 60% increase in cancer incidence rates over the next two decades, it could become the leading cause of death (surpassing heart disease) soon enough.
Treatment is the biggest challenge
A number of cancer types have yielded strong improvements in survival over the past three decades. In select cancer types, researchers have established a stranglehold on the risk factors and pathways by which they operate, leading to more effective treatments and people paying heed to avoid high-risk factors when applicable.
For example, five-year survival rates for breast cancer and prostate cancer, two cancers that account for close to 30% of all cancer diagnoses in the U.S. per year, have improved to 90% and essentially 100%, respectively, after clocking in at 75% and 68% in the 1975-1977 timeframe, based on data from the American Cancer Society.
One of the biggest challenges that remains when treating cancer, especially metastatic cancer that has spread throughout the body, is how to effectively target tumors while causing as little damage to healthy cells as possible. Global chemotherapy treatments, which are often administered through IV or as a pill, do slow tumor growth, but they also make patients sick because they interfere with healthy cell reproduction too. Thus, physicians are constantly struggling between wanting to use a combination of chemotherapy agents that would likely be effective against a certain type of tumor, and the patient being unable to receive a global chemotherapy treatment because few people with metastatic disease are capable of dealing with the nasty side effects of global chemotherapy treatment.
But, the good news, in case you missed it this past week, is that researchers at Virginia Tech may have devised a completely new method of delivering chemotherapy to cancer patients with solid tumors that could significantly reduce healthy cell death and pack more of a punch to the tumor.
An entirely new way to dose cancer patients
According to a study published in Science Translational Medicine by lead author James Byrne and his team of some two dozen study contributors, a new process known as iontophoretic delivery could be the key to focusing chemotherapy agents toward tumors and away from healthy cells.
Instead of delivering chemotherapy via IV or pill, researchers developed a device, complete with a chemotherapy reservoir of Gemzar, which was implanted directly into a tumor. Then, the device was turned on and stimulated using an electric field, causing the chemotherapy to leave its reservoir and focus on the tumor.
In its study, Virginia Tech researchers used three mouse models: one model implanted with human pancreatic cancer, and the other two with aggressive forms of breast cancer. Additionally, one canine model was assessed.
In the pancreatic cancer model, mice treated with the device that received Gemzar bi-weekly saw a mean log reduction in tumor volume compared to an increase for mice solely given Gemzar, or put on an IV saline solution. Similar results were observed in the breast cancer studies, with co-administration of cisplatin therapy in addition to the device doubling survival. Researchers note that when radiation therapy was added, survival was even further extended. Lastly, when Gemzar was delivered via device in canines, local drug concentrations in the tumor were sevenfold higher than if administered by an IV, while systemic drug levels of Gemzar were 25 times lower.
The English translation of the data above is this: The ionophoretic delivery device increased chemotherapy delivery to tumors, it decreased chemotherapy levels found throughout the rest of the body (the undesired target area), and it helped improve survival when combined with current standards of care, including chemotherapy and/or radiation.
Focused therapies are on the way
For anyone with cancer, advanced disease or not, this is potentially game-changing news. But, there are also a number of tumor-focused therapies already on the market or working their way through clinical trials that could soon make a genuine difference in cancer patients' quality of life.
I can think of three pathways in particular targeted at reducing healthy cell death and increasing chemotherapy dosing directly to tumors. These include antibody-drug conjugates, hypoxic-targeting drugs, and cancer immunotherapies.
Antibody-drug conjugates, or ADCs, use special linking technology to attach a chemotherapy toxin to an antibody. These antibodies then seek out cancer cells and release the toxin once they come into contact with a specific protein signature given off by cancer cells. Perhaps the most well-known ADC compound is ImmunoGen's (NASDAQ:IMGN) and Roche's (OTC:RHHBY) Kadcyla.
Kadcyla is currently approved by the Food and Drug Administration as a second-line treatment for HER2-positive late-stage breast cancer. In the clinical studies that led to its approval, Kadcyla improved median progression-free survival (i.e., stable disease) to 9.6 months from 6.4 months and boosted median overall survival by 5.8 months to 30.9 months.
It's worth noting, though, that Kadcyla also had a recent setback in its MARIANNE study. Kadcyla performed on par in terms of median progression-free survival with the control combo of Herceptin and a taxane chemotherapy in first-line indications when Wall Street was clearly looking for a statistical advantage for Kadcyla. Chances are still good that Kadcyla will be a critical cancer-fighting drug for years to come.
Hypoxia-targeting drugs are another unique therapy currently working their way through clinical studies.
Generally, when healthy cells are formed, blood vessel growth can keep pace, leaving everything in a sort of harmony. However, since tumor growth occurs without rhyme or reason, it can occasionally outpace blood vessel growth, leaving certain regions of a tumor starved for oxygen, or hypoxic. Hypoxia-targeted drugs focus in on these low-oxygen regions and attack. Because hypoxia is rarely witnessed in healthy cells, it should result in minimal healthy cell death.
The name to watch here is Threshold Pharmaceuticals (NASDAQ:THLD) and its lead hypoxia compound TH-302. It's currently being examined in 10 clinical studies (mostly early stage) with the three most intriguing being a mid-stage study for non-squamous non-small cell lung cancer, a late-stage study for soft tissue sarcoma, and the MAESTRO trial examining TH-302 in combination with Gemzar as a treatment for pancreatic cancer. This last study is particularly critical as pancreatic cancer has few effective treatment options.
Lastly, drug developers are working on a new class of drug that looks to enhance the body's immune system so it can better recognize and fight cancer.
One of the reasons cancer is so difficult to kill is that it has developed an effective mechanism to hide itself from the immune system. A late-stage drug known as bavituximab being developed by Peregrine Pharmaceuticals (NASDAQ:PPHM) is looking to change that.
Peregrine's bavituximab is a phosphatidylserine (PS)-targeting monoclonal antibody that's looking to turn the tables on non-small cell lung cancer in a trial as a second-line treatment. Generally, healthy cells express PS on the inside of their cellular wall, protecting them from the body's immune system. However, this immunosuppressive molecule is found on the outside of cancer cells and protects the cancer cell from attack by the immune system. Bavituximab aims to block this immunosuppressive response and allow the immune system to do its work.
Although Peregrine's midstage study wasn't without a lot of unneeded drama, bavituximab led to a median overall survival of 11.7 months in phase 2 trials compared to just 7.3 months for the docetaxel control group.
Headed in the right direction
Between the findings by researchers at Virginia Tech and the aforementioned three pathways, it's apparent we're on the right path to improving patient quality of life and, hopefully, survival. I look forward to ongoing research that looks at new ways to deliver chemotherapy in a safer and more directed manner, and to the development of new treatments that extend patients' lives.