The Effects of Placebos in Cancer

Author Jo Marchant (photo credit: Garry Simpson/Crown)

Science writer Jo Marchant has written a fascinating book examining the role of the mind in healing. In her book “Cure: A Journey Into the Science of Mind Over Body“, Marchant separates the fact from fiction when it comes to mental strategies —and accidental benefits— when it comes to healing. This includes everything from meditation to prayer to the placebo effect.

The bottom line? Mental strategies usually help heal the body, and sometimes in profound ways rivaling medical interventions. Of course the underlying disease dictates the degree to which mental strategies show efficacy. Clearly, a placebo pill alone is not going to fix a compound fracture. But the effects of mental strategies are still surprising and intriguing, especially considering that most mental strategies have no adverse side-effects and no cost.

Studies have shown that pill size, color, and perceived cost all play significant roles in a treatment’s perceived effectiveness. A study of placebos in JAMA in 2008 showed that 85% of healthy volunteers found the “more expensive” pain reliever more effective, compared to 61% who used the “cheaper” pain reliever. All of the pills in this study were placebos, and contained no pain relief medicine. The fact that people found any pain relief at all is surprising. Researchers at the University of Cincinnati in 2015 found the same results in a much more serious setting: Parkinson’s disease. Other studies have shown that placebos sometimes even work when patients know they are taking placebos.

One of the most consistent benefits mentioned in Marchant’s book comes from compassion. Patients with friendly, supportive teams of family, friends and medical practitioners, do better as a group than those who do put together an effective team. Not surprisingly, patients seeing doctors with a good “bedside manner” generally do better than those who see cold, impersonal, doctors.

There is a growing body of science helping to explain why perception and other mental strategies have physiological effects. Many mental strategies such as visualization, meditation and prayer, have obvious benefits such as lower heart rate, blood pressure and stress levels. Many strategies have been examined in multiple, large clinical studies. Several peer reviewed studies have even tried to explore the science of prayer. Prayer has been shown to have “relaxation response” benefits similar to meditation. It should be noted, however, that intercessory prayer (praying for someone other than yourself) shows no statistical benefit if the patient is unaware of the prayer. Patients aware that someone is praying for them feel compassion, and thus receive a benefit.

The ramifications to cancer patients are also profound. If you view cancer prevention and therapy as probabilistic, where every potential benefit makes it more likely that you will succeed, a 5% gain is important. And there are many indications that mental strategies can result in benefits greater than 5%.

In 2009, Johns Hopkins published a large study of 1052 patients with high grade astrocytoma patients, which includes grade III and IV brain cancers. Their results showed that depression could affect overall survival by 20% or more, independent of treatment modality or degree of disability. This is an astounding figure, considering that many chemo drugs have lower efficacy rates, and hints at the importance of treating mental health during cancer treatment.

The ramifications of mental health strategies in cancer may be even more profound than currently realized, especially if some intriguing studies can be translated into therapies.

Scientists at MIT have discovered that rats who are raised in a low-stress environment produce more HDAC (histone deacetylase) inhibitors in their brains (or something which causes the equivalent result), while rats raised in stressful environments (with all other controls being equal) produce less. The difference may involve the same relaxation response as we see in meditation. Scientists were able to reverse an Alzheimer’s-like condition in the rats, simply by lowering their stress levels. The ramifications are potentially very important for cancer patients, because of the benefits of HDAC inhibitors both as radiosensitizing and therapeutic agents. Several HDAC inhibitors are already approved in cancer patients, including vorinostat (SAHA).

References:

• http://www.nytimes.com/2016/01/25/books/review-in-cure-accepting-the-minds-role-in-a-bodys-health.html?_r=0
• http://www.npr.org/sections/health-shots/2016/01/26/464372009/how-meditation-placebos-and-virtual-reality-help-power-mind-over-body
• http://www.nytimes.com/2008/03/05/health/research/05placebo.html
• http://www.latimes.com/science/sciencenow/la-sci-sn-expensive-placebos-work-better-20150127-story.html
• http://www.ncbi.nlm.nih.gov/pubmed/18786716
• http://www.medscape.com/viewarticle/529308
• http://www.mja.com.au/public/issues/186_10_210507/jan11101_fm.html

Making Cancer Tumors Light Up for Surgeons

Tags

brain, cancer, chlorotoxin, melanoma, skin cancer, Tumor Paint

What if surgeons could see a color-coded map on tissue, showing them where to work and what to avoid? That’s a goal oncologist Dr. Jim Olson has been trying to make reality for over a decade.

Tumor Paint in a mouse brain (the blue-green glow)

Using a unique molecule called chlorotoxin derived from the venom of the Deathstalker scorpion (L. quinquestriatus), Olson’s team figured out how to make cancer tumors glow. The idea is so exotic that it’s hard to believe, and for many years it was difficult for Olson to find funding for the research. When I first met Olson in 2009, he was busy with new research and another biotech startup, but he lit up, no pun intended, at the opportunity to talk about Tumor Paint. Today, Tumor Paint is in 2 clinical trials in humans, testing it in brain tumors and skin cancer.

Scorpion venoms have been used medicinally for perhaps thousands of years in China and India, but it wasn’t until 1993 that a team at Harvard identified and named chlorotoxin, which by itself is harmless to humans. Chlorotoxin is actually a peptide—a chain of amino acids which may have originally evolved to allow scorpions to paralyze the muscles of cockroaches. The following year, an MD-PhD student at the University of Alabama named Nicole Ullrich (now at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center) theorized and then proved that the newly defined chlorotoxin would bind to glioma brain cancer cells but not normal, healthy cells. This remarkable insight soon resulted in the first experimental cancer treatment, called radiolabeled TM-601, to use the properties of chlorotoxin.

Tumor Paint is a conjugated molecule consisting of the key components of chlorotoxin and Cy5.5, a cyanine dye with fluorescence. Because chlorotoxin has a high affinity for matrix-metalloproteinase (MMP-2), an enzyme which is activated and often upregulated in several virulent cancers, it homes in on cancer cells rather than healthy cells. Olson has found Tumor Paint accumulating in tissue as small as 200 cells, giving it an unusually high level of detail, especially when compared to common scanning methods such as MRI. When near-infrared light is shown on tissue infused with Tumor Paint, the cancerous tissue glows.

BLZ-100 (Tumor Paint)

In July, 2013, a unique partnership began between the Fred Hutchinson Cancer Center in Seattle and the privately held biotech company Blaze Bioscience, to refine and commercialize Tumor Paint, now called BLZ-100. First Blaze won approval to test BLZ-100 in dogs, where it also found success. Today, BLZ-100 is in 2 human phase I clinical trials trying to determine the ideal dosage. A skin cancer trial is being conducted in Australia and a brain tumor trial in both Australia and the U.S. The U.S. trial, which has already treated half a dozen patients, is being conducted at Cedars-Sinai Medical Center under Dr. Chirag Patil.

References:

• http://www.npr.org/blogs/health/2013/09/12/221060071/why-painting-tumors-could-make-brain-surgeons-better
• http://abc2.org/article/fda-approves-scorpion-venom-based-tumor-paint-brain-tumor-clinical-trial
• https://www.fredhutch.org/en/news/releases/2013/07/blaze-bioscience-collaboration-optides-discovery-program.html
• https://www.fredhutch.org/en/diseases/featured-researchers/olson-jim.html
• http://www.wired.com/2014/06/scorpion-venom/
• http://www.blazebioscience.com/

Novocure’s Optune is a Ground-breaking Brain Tumor Treatment

Tags

brain, cancer, glioblastoma, glioma, tumor

Recently, in December, 2014, the privately-held company Novocure announced extremely positive results for its Phase III trial in glioblastoma, the most common and aggressive type of brain tumor. Novocure’s EF-14 Phase III trial was terminated early because of early success in newly diagnosed glioblastoma patients. Novocure previously found similar success in a Phase III trial of recurrent glioblastoma patients in 2010.

Novocure’s Optune treatment (formerly called NovoTTF-100A) has been available in many countries since its 2010 Phase III success, and was approved by the US FDA in 2011 for recurrent glioblastoma. The non-invasive Optune treatment consists of a portable battery pack and circuitry connected to the patient’s scalp via electrodes. The electrodes deliver low intensity, alternating electric fields within the frequency range of 100-300 kHz. At this frequency, the electric fields can not be felt by the patients, and cause no harm to healthy cells. But after years of research in Israel, it was discovered that these frequencies cause apoptosis (cell death) in cancer cells.

Novocure’s Optune device is a ground-breaking, paradigm-shifting, toxicity-free treatment for glioblastoma brain tumors.

While the treatment does require the patient to carry the equipment and affix electrodes to a shaved head, the treatment causes no pain or side effects, and is a classic example of the huge growth in transformational, paradigm-breaking cancer treatments the world has enjoyed over the past decade.

The EF-14 Phase III trial used Optune in 315 newly diagnosed glioblastoma patients with standard temozolomide treatment. The improvements in median progression-free survival (PFS) and overall survival (OS) were modest in actual time, but very significant relative to the aggressive nature of the disease. Most importantly, the long tail distribution showed 43% of patients still alive after 2 years from diagnosis, compared to only 29% with standard treatment. Standard chemo/radiation treatment for newly diagnosed glioblastoma patients has a median OS of only 14.2 months, so this form of cancer is in desperate need of new ideas and strategies. Over 10,000 people a year in the US alone are diagnosed with glioblastoma. Optune is now available at over 150 cancer centers in the US.

Novocure’s Optune device is a ground-breaking, paradigm-shifting, toxicity-free treatment for glioblastoma brain tumors. Optune has proven to have additive benefits when used with other treatments, giving more credence to the benefits of combined, multi-pronged treatment strategies.

In 2011, Novocure chairman Bill Doyle presented an overview of the Optune system’s mechanism at a TED conference.

References:

• http://www.novocure.com
• http://www.biomedcentral.com/1756-6649/9/1