What is Personalized Cancer Therapy?

Personalized therapy is the right treatment, at the right dose for the right patient. Like the weather, however, it seems that everyone’s talking about it, but no one is doing anything about it.

In its simplest form personalized care is treatment that is designed to meet an individual’s unique biological features. Like a key in a lock, the right drug or combination opens the door to a good outcome.

Lock & Keys 1When over the years I lectured on the development of the cisplatin/gemcitabine doublet, my two boys were quite young. I would show a slide depicting a doorknob with a key in the keyhole. I likened our lab’s capacity to identify sensitivity to the cisplatin/gemcitabine combination as “unlocking” an individual’s response.

At the time my wife and I would leave the key in the inside of the front door enabling us to unlock it when going out. We reasoned at the time that our 2-year-old would not be strong enough, nor tall enough to turn the key and let himself outside. We reasoned wrong, for one day our son Alex reached up, turned the key and opened the door right in front of us. Lesson learned: Given the right key, anyone can open a door.

I continued my analogy by saying that even Arnold Schwarzenegger would be unable to open a door given the wrong key, but might, if he continued trying, snap it off in the lock.

The right key is the right treatment, effortlessly unlocking a good response, while the wrong key is the wrong treatment more often than not too much, too late, akin to a solid tumor bone marrow transplant.

In recent years, personalized care has come to be considered synonymous with genomic profiling. While we applaud breakthroughs in human genomics today, there is no molecular platform that can match patients to treatments. The objective response rate of just 10 percent, almost all in breast and ovarian cancer patients in one study (Von Hoff J Clin Oncol 2010 Nov 20:28(33): 4877-83), suggests that cancer biology is demonstrably more complex than an enumeration of its constituent DNA base pairs. The unilateral focus on this area of investigation over others might be described as “the triumph of hope over experience” (James Boswell, Life of Samuel Johnson, 1791).

But hope springs eternal and with it the very real possibility of improving our patients outcomes. By accepting, even embracing, the complexity of human tumor biology we are at the crossroads of a new future in cancer medicine.

William Withering (1741-1799) the English physician and botanist credited with discovering digitalis as the therapy for dropsy, e.g. congestive heart failure (An Account of the Foxglove and some of its Medical Uses, Withering W. 1785), had absolutely no idea what a membrane ATPase was, when he made his remarkable discovery. It didn’t matter. Cardiac glycosides provided lifesaving relief to those who suffered from this malady for fully two centuries before Danish scientist, Jens Christian Skou, identified these membrane bound enzymes, for which he was awarded a Nobel Prize in 1997.

Similarly, penicillin, aspirin, and morphine were in all use for decades, centuries, even millenia before their actual modes of action were unraveled. Medical doctors must use any and all resources at their disposal to meet the needs of their patients. They do not need to know “how” something works so much as they (and their patients) need to know “that” it works.

The guiding principle of personalized medicine is to match patients to therapies. Nowhere in this directive is there a prescription of the specific platform to be used. Where genomic signatures provide useful insights for drug selection, as they do in APL (ATRA, Arsenic trioxide); NSCLC (EGFr, ROS1, ALK); CML (Imatinib, Dasatanib) then they should be used.

However, in those disease where we haven’t the luxury of known targets or established pathways, i.e. most human malignancies, then more global assessments of human tumor biology should, indeed must, be used if we are to meet the needs of our patients. Primary culture analyses like the EVA-PCD® provide a window onto human tumor biology. They are vehicles for therapy improvement and conduits for drug discovery. Scientists and clinicians alike need to apply any and all available methodologies to advance their art. The dawn of personalized medicine will indeed be bright if we use all the arrows in our quiver to advance clinical therapeutics and basic research.

Reposted from May 2012

What Can You Do to Improve Your Odds Against Cancer?

I sometimes joke with my patients that a new diagnosis of cancer rarely provides them enough time to get an MD or PhD. Yet it is that level of preparation that may be required to answer the myriad questions that lie ahead.

Although it’s a joke, it is only partly in jest. Unlike buying a house or a car for which one’s life experiences can prepare you, medicine is opaque, complicated and ever changing. At the bleeding edge of medical complexity sits medical oncology and its dizzying array of genomics, transcriptomics, proteomics, epigenomics and metabolomics. Not only is it difficult for patients to keep up with all the changes, it is increasingly beyond the ken of their doctors who have spent entire careers training in the specialty, many of whom may have an MD and a PhD.

So how can patients improve their odds when the obstacles seem so daunting?

notebook-clipart-red-spiral-notebookMy first recommendation is that you develop a personal diary or record book of the procedures, staging studies, pathologic diagnosis, tumor markers, and physician recommendations. This can be accomplished by requesting that your doctors provide either electronic or physical copies of CT scans, pathology reports, blood tests and other clinically relevant information. While there has been some controversy surrounding their overuse, I am a believer in the simple blood tests used as barometers of your cancer with names like CEA, CA19.9, CA125, CA27.29, and CA 15.3. Although they are not perfect, they are easy to obtain, relatively inexpensive and can be repeated regularly to assess progress with therapy.

The second thing that I recommend is that you gain a working knowledge of your diagnosis. While there are no lung cancer search resultsperfect sources of information, the internet can provide useful basic information as a starting point. Begin by obtaining from your doctor the most accurate definition of the cancer. If it is breast cancer, is it infiltrating ductal or lobular? Are you ER positive? Is your tumor HER-2 positive? If it is stomach cancer, is it intestinal type or diffuse, etc? This will facilitate your searches, as well as your future conversations with consultants.

Once you know what you’ve got, the next thing you will need to know is where it is. That is what is known as your stage. The older classification used Roman Numerals I-IV with local disease (early) as stage I and metastatic (disseminated) as stage IV. The more modern system is known as TNM, where T stands for tumor size (1-4), N stands for lymph involvement(1-3), and M stands for metastatic involvement (0 or 1). Most contemporary pathology reports include TNM staging. With the diagnosis and stage established, you now know what you have and where it is.

This is where it gets interesting. Now, what do you do about it?

It is at this point that therapeutic choices must be made. Most physicians will rely upon standard established guidelines. Among the most widely used guidelines are those published by the National Comprehensive Cancer Network known as NCCN. While these guidelines can be useful, they can also be stultifying, limiting patients to what might be considered the lowest common denominator of care. While they may be better than haphazard treatment selection, they may very much miss the mark for your unique needs.

Here the process degenerates into a plethora of confusing choices.

Should you have genomic profiling? If so, should it be based on a tissue biopsy, circulating cell free tumor analysis, or even the newer urine tests that measure the presence or absence of abnormal genes? All of these technologies have merit and over the coming years the best ones will shake out. Despite these tests being widely touted (and profitable for the purveyors), none of these test have been put to formal trials that establish their capacity to influence survival. This is interesting because many of these tests have obtained insurance and Medicare coverage without even remotely rising to this standard. Nonetheless, these tests can be used for specific diseases like lung and leukemia where actionable targets are known to exist. Beyond that, caveat emptor (buyer beware).

One of the problems with genomic profiles is that they do very good job of telling you what the problem may be, but a very bad job at telling you the solution. It is a rare genomic mutation that comes with a drug to treat it. Most of the findings wind up asking more questions rather than providing more answers.

With the diagnosis established, the stage known and in certain circumstances molecular profiles complete, it is time for you to choose treatments and the centers that will provide them. Many seek the care of academic centers. These centers may offer clinical trials as a first line therapy for those who meet criteria.

NCI Clinical TrialsIt should be remembered that clinical trials are conducted in three principal formats. Phase I trials examine brand new drugs. These trials determine the safety of the drugs at different dose schedules. Phase II trials take the established safe doses and develop experience in each type of disease, e.g. lung versus colon versus breast. Phase III trials then compare the new drugs with existing treatments to see if there is any real improvement.

It is critical to recognize the functions of these different types of trials. Phase I studies classically have no therapeutic intent (your benefit is secondary to their measurement of your ability to tolerate the drug).

Phase II trials seek evidence of clinical activity by disease, but your specific disease may not be right for that drug.

Finally, Phase III allows a comparison of standard treatment to the new one. Many of these drugs do not make the grade and fall off the development wagon. In addition, you must be willing to be randomly assigned.

It is here that my approach diverges from those outlined. I have long maintained that each patient is unique and that their cancers must be treated individually. Recognizing that no genomic, proteomic or transcriptomic platform can answer the very complex questions of therapeutic response, we at Rational Therapeutics have developed functional analyses through the use of the EVA-PCA assay, which studies each patient’s tumor by exposing it to the drugs of interest. The most active, least toxic combinations are then recommended. In a report at the American Society of Clinical Oncology meeting of 2013, we showed a 2.02 higher response rate (P < 0.001) and a 1.44 improvement in one year survival (P < 0.02) for patients who received assay-guided therapy. This established the predicative validity of the functional approach.

It is important for patients to realize that cancer is an unbalanced system, not just an abnormal cell. Cancer as a disease goes beyond the cell or even the tumor to affect the body itself. Alterations in immunity, metabolism and physiology contribute to the good or bad outcomes of every patient. Patients should seek to normalize their lifestyle, improve their diets, maintain an active exercise program, reduce their weight to lean body weight, and may in some circumstances consider nutritional supplements and/or appropriately selected natural products that may augment their wellbeing.

The human body is a complicated machine and each part resonates with every other part. A good diet, a good night’s sleep and avoidance of an unhealthy lifestyle, as much as they may sound like your mother’s advice, is indeed very good advice.

Every cancer patient has the right to get better. As a patient, you should take charge of your cancer and make smart decisions. Afterall, no one is more interested in saving your life than you.

In Cancer Research: An Awakening?

In 2005, as the Iraq War reached a low point with casualties mounting and public support dwindling, Sunni tribesman in the Anbar Province arose to confront the enemy. Joining together as an ad hoc army these fighters turned the tide of the war and achieved victories in the face of what had appeared at the time, to be overwhelming odds.

I am reminded of this by an article in The Wall Street Journal by Peter Huber and Paul Howard of the Manhattan Institute that examined the bureaucracy of drug development. It raised the question: Are new cancer treatments failures or is the process by which they are approved a failure? They describe “exceptional responders” defined as patients who show unexpected benefits from drug treatments. Using molecular profiles, they opine, scientists will unravel the mysteries of these individuals and usher in an era of personalized medicine. Thus, rigid protocols that use drugs based upon tumor type e.g. lung vs. colon fail because they do not incorporate the features that make each patient unique – an awakening.

The example cited is from Memorial Sloan-Kettering where a patient with bladder cancer had an unexpected response to the drug Everolimus (approved for kidney cancer). Subsequent deep sequencing identified a genetic signature associated with sensitivity to this drug. While it is a nice story, I already knew it very well because it had been repeated many times before and would in the past have been dismissed as an “anecdote.” It is precisely because of its rarity that it has been repeated so many times.

The WSJ analysis strikes a familiar chord. For decades, we have decried the failure of rigid clinical trials that underestimate a patient’s unique biology yet cost millions, even billions of dollars, while denying worthy candidates new treatments under stultifying disease-specific designs.

Well Tray Closeup2 smallWe pioneered phenotypic (functional) analyses (the EVA-PCD platform) to examine whole cell models as we explored drug response profiles, novel combinations and new targets. It is regrettable that these WSJ authors, having raised such important issues, then stumble into the same tantalizing trap of molecular diagnostics, and call for bigger, better, faster genomic analyses.

Cancer patients need to receive treatments that work. They do not particularly care why or how they work, just that they work. These authors seem to perpetuate the myth that we must first understand why a patient responds before we can treat them. Nothing could be further from the truth.

Alexander Fleming knew little about bacterial cell wall physiology when he discovered penicillin in 1928, and William Withering knew nothing about the role of muscle enzymes in congestive heart failure when he discovered digoxin extracts in 1785. Would anyone argue that we should have waited decades, even centuries to apply manifestly effective therapies to patients because we did not have the “genes sequenced?’

We may be witness to an awakening in cancer drug development. It may be that a new understanding of individualized patient response will someday provide better outcomes, but platforms with the proven capacity to connect patients to available treatments should be promoted and applied today.

Truly Personalized Cancer Care

In the mid 1980s, it became apparent to me that cancer did not result from uncontrolled cell proliferation, but instead from the lack of cell death. Yet, cancer research labored for almost a century under the erroneous belief that cancer represented dysregulation of cell proliferation. Today, we confront another falsehood: the complexities and redundancies of human tumor biology can be easily characterized based on genomic analyses.

The process of carcinogenesis reflects the accumulation of cellular changes that provide a selective survival advantage to transformed cells.  However, the intricate circuitry that provide these survival advantages, reflect harmonic osolations between DNA, RNA and protein. Put simply, Genotype does not equal Phenotype. It is the phenotype that determines biological behavior and clinical response in cancer. Thus, it is overly simplistic to imagine that a DNA profile by itself can provide more than a fraction of the information required to make individual patient treatment decisions.

Colon cancer

Colon cancer

When therapies are based on genomic analysis, only a portion of the patient’s profile is taken into consideration. These analyses disregard the environmental, epigenetic and proteomic factors that make each of us individuals. Though useful prognostically and applicable in select circumstances where a unique genetic perturbation leads to a clinical response (c-ABL and Imatinib response in CML), genomic analyses provide only a veneer of information.

The Rational Therapeutics Ex Vivo Analysis – Programmed Cell Death™ (EVA-PCD) assay focuses upon the complexity of human tumors by measuring cell death, the end result of all cellular mechanisms of response and resistance acting in concert. By incorporating cell-cell, vascular, stromal and inflammatory elements into the tumor response assessment, the EVA-PCD platform provides a robust surrogate for human tumor response. While much of modern cancer research pursues the question of “Why” cancer arises, the clinical oncologist must confront the more practical question of “How” the best outcome can be achieved.

Assay-directed therapy is truly personalized cancer care providing treatments unique to the individual.

 

Reblogged from February 2010.

Cancer Patient’s Need to Know – Whose Avatar is it?

The 1984 celebrated case of Baby Fae described the efforts of intrepid investigators at Loma Linda University in California to save the life of an infant born with a hypoplastic heart (the left side of the heart was severely underdeveloped). To salvage this unfortunate child, the heart of a baboon was transplanted into her chest, which successfully maintained her cardiac function. Unfortunately, the child died 21 days later after rejecting the heart.

The experience nonetheless spawned a lively discussion of ethics in human experimentation and the lengths to which we will go to save a life. A friend residing in New York contacted me shortly thereafter. Knowing that I was in medical training in California, he was intrigued by this report and posed the question. “What is the fastest animal in the world?” When I suggested a cheetah or African gazelle, he answered “No, a baboon running past Loma Linda Medical Center.”

I am reminded of this quip following a news report about Champions Oncology. This biotech company located in Hackensack, NJ, founded by investigators from Johns Hopkins University has developed a technique to transplant human tumors into immunocompromised (known as nude for their loss of hair) mice to test drugs and combinations. They use the term “avatar” to describe these human-tumor-bearing mice and like their video-game counterparts these mice serve as surrogates for their patient “users.” It takes 20 to 30 mice to complete the analyses for each patient. Although the work is based on sound science, the practicality, predictive validity and ultimate utility of this approach has yet to be established. This has not dampened the enthusiasm of desperate cancer patients who have proven willing to spend tens of thousands of dollars to undergo a Champion analysis.

Nude-mouseSo what are the upsides of the avatar model? For one, this is a living organism with a functioning blood supply, liver, kidneys and the capability of metabolizing pro-drugs (precursor) into active species. The process utilizes cell clusters, not individual single cells in their analysis. Responses are ultimately “phenotypic” in as much as they reflect cellular responses to injury and not genotypic profiles. Finally, toxicities can also be assessed by measuring the animal’s tolerance of the drug or combination administered.

But let’s drill down for a moment and take a closer look. The avatar approach requires months of preparation, the operation of a vivarium (animal zoo) and several mice for every single drug or combination tested. It requires prolonged (many months) maintenance of the animals with highly unpredictable engraftment of the transplanted tumors. Furthermore, significant time, energy and skill are needed to maintain these in-vivo systems.

Ultimately, only a handful of drugs can be examined, lest the number of mice required becomes unmanageable. At the end of the day these investigators are making a valiant effort to approximate work that we, and our colleagues, have successfully conducted for more than two decades – the accurate selection of chemotherapies and drug combinations for individual patients.

If we allow for the obvious downsides of expense, difficulty, time, limited sample size, low efficiency and resource intensity required to conduct even a single patient’s study there are more daunting concerns.

First, these cells are not actually in their “native state.” Over a period of time the tumors will no longer be host to human immune cells, nor will they be exposed to human cytokines and VEGF. The observed growth of the implanted tumors in the mice-avatars may, in part, reflect an ingrowth of mouse-derived fibroblasts and blood vessels, which have distinctly different biology from those of a human host.

Even if we accept the expense and difficultly of avatars, there is no clear evidence on an individual patient basis, that this approach holds any advantage over the much simpler and direct evaluation of human primary culture microspheroids. That is, the avatar approach appears to be a difficult, cumbersome, inefficient and a very expensive way to do something that we can already do inexpensively, rapidly and efficiently. Further, the purported advantages of in vivo-avatar system are actually less than meets the eye.

After all, most clinical drugs have “active” derivatives that can be utilized for testing in short-term culture without the need for a mouse liver. Our careful calibration of in vitro drug exposures against actual patient responses (P < 0.001) has established the predictive validity of these culture conditions. Finally, the toxicities of virtually all clinically relevant drugs that patients would request for testing (and likely receive) are already well-known to clinicians from existing Phase I and Phase II clinical data sets.

Human tumor sensitivity to chemotherapy (or targeted agents) is driven by what might be described as “response elements.” These unique features of each patient’s tumor can be accurately probed at the phenotypic level through the use of simple assays conducted in short-term culture. Our microspheroid model has proven highly predictive of clinical outcome in virtually every tumor type ever tested.

Our analyses are conducted in seven days, with samples that are the same size or smaller than those required for avatar generation. Furthermore, short-term platforms can analyze dozens of drugs and combinations at a price that is far less expensive. While it might be argued that avatars, once established, can be used as repositories for future research, that is small comfort to patients in need of immediate answers who find themselves paying handsomely for a service that will not be available in a timely manner, e.g. that which can help them in their need for immediate drug selection.

It seems that the medical science community is less interested in results than process. The fact that short-term cultures are predictive of clinical outcome seems less important than the provocative scientific results that these avatar models can provide Avatars enable scientists to interrogate cancer cells for genomic and proteomic signals, offering the opportunity to conduct interesting science. But has that science become more important than the clinical utility of the tests that were purportedly developed (and sold) to improve patient outcomes?

Patients who are considering spending tens of thousands of dollars for these glorified chemosensitivity tests would do themselves a service to first carefully examine the predictive validity, breadth of data, cost and turn-around-time of short-term culture methods, like the EVA-PCD® assay before they commit their precious time and resources to so “interesting” an endeavor as an avatar analysis. After all, it is the patient and their good outcome that should be at the top of the list when the advantages of any system or method are being weighed. Truly personalized cancer care should be just that – personalized.

With the rise of avatars it may be timely to re-examine the original question and wonder whetherNude-mouse the fastest animal in the world will soon be a nude mouse running past Johns Hopkins University.

Rare Tumors – Challenges and Triumphs

When I am asked how our EVA-PCD laboratory platform might best be applied, I have several responses.

On the one hand, there is my catchphrase, “we cure the curable, treat the treatable and avoid futile care.” What I mean by this is that patients with potentially curable malignancies, e.g., small cell lung cancer, previously untreated ovarian, non-Hodgkin lymphoma, and some leukemias should receive the most effective treatment first line, in order to enhance the likelihood of a cure.

The majority of our patients fall into the second category, those whose tumors can be treated but are less likely to be cured. They include recurrent breast, newly diagnosed lung or pancreas, and colorectal cancer among others.

Finally, in those patients for whom very few options exist, it is arguable that they are best served, when found drug resistant, by avoiding the toxicity of ineffective therapy, or what is known as futile care.

The other way I describe our platform is to explain its capacity to explore treatment options where no reliable guidelines exist. These rare malignancies offer the opportunity to examine a broad array of treatment options, including signal transduction inhibitors in pursuit of heretofore-unrecognized therapeutic directions. Just such a case was submitted to our laboratory this spring

The patient, a 56-year old woman from Brazil, presented in February with a large mass in the left axilla. Biopsy confirmed for an ER, PR and HER2 negative (triple negative) epithelial neoplasm with a proliferative index of 80 percent. The only positive findings were p63 antigen and cytokeratins. Work-up revealed extensive metastatic disease but no other primary could be identified.

The patient underwent surgery followed by aggressive multi-agent chemotherapy. The disease rapidly progressed. Second line therapy proved ineffective. At this point a tissue sample was submitted to our lab. The EVA-PCD analysis revealed an unusual profile with a high degree of activity for sorafenib combinations.  Sorefenib was originally developed as BRAF inhibitor and ultimately received FDA approval for the treatment of advanced kidney and liver tumors, associated with the drugs cross reactivity as a VEGF inhibitor. The patient’s study also revealed persistent activity for the beta tublin inhibitors vinorelbine and paclitaxel. The treating physician used our profile to create a novel combination of vinorelbine, paclitaxel combined with sorafenib.

The pretreatment PET CT obtained in June, revealed complete replacement of the liver and extensive soft tissue and nodal metastasis to the lungs, mediastinum, retroperitoneum, as well as innumerable boney metastasis. After failing the previous chemotherapies the patient began this novel drug combination in mid June.

When I arrived in my office this week, I was met with an email that had as an attachment a slide set from a tumor board presentation that described this patient. The introductory slide was, “Tumores Raros.”(Portuguese for Rare Tumors)  Included in the presentation was the patient’s history, pathology, immunohistochemistry, treatment overview and serial CT/PET scans. The final slide compared June 2013 PET CT (taken before she began our combination) with an August 2013, (taken after 2 cycles of therapy). The results could not have been more different.  The patient had achieved a complete remission. Gone was the extensive hepatic disease. Gone were the boney metastasis. Gone were the dark nodal mets that had scattered across her torso and abdomen like shotgun pellets on an x-ray image. Contrary to every expectation this patient had responded to a drug combination that no one had ever heard of.  No one including her treating physician and me.

These experiences remind us that every patient is a unique story, unfolding in real time. This is a stellar example of personalized cancer care, a gleaming testament to the laboratory’s capabilities and even more so to the dedication of the treating physician who broke with all tradition to treat this patient correctly. I am honored to work with this courageous colleague and delighted by this spectacular outcome.

ASCO Update: Personalized Cancer Care – Our Contributions

ASCO logo

As part of our ongoing blog postings we like to include recent presentations and publications. On July 9, I described our ASCO presentation exploring crizotinib, “Functional Profiling Leads to Identification of Accurate Genomic Findings.

To conclude the review of our other presentations from that meeting, here is a brief summary of our work.

The first of the two was our international collaboration in personalized medicine for the treatment of advanced and drug-refractory cancers: “Clinical application of human tumor primary culture analyses.” The study reviewed the results of 67 patients from institutions across Brazil.

Tumor samples were transported by overnight courier to California for drug response profiling. A broad array of tumors were included. The overall success rate provided actionable results in 62 of 67 patients (92 percent). More than 75 percent of the studies provided results for between 8 and 16 drugs and combinations with a median of 12 reported. Several strikingly good responses were observed, including novel combinations identified in the laboratory. This study confirms the feasibility of international collaboration and reflects the globalization of medical care delivery.

The final study published by ASCO was also a collaborative effort with SageMedic of Larkspur, CA, The Ludwig Maximilians University Munich, Germany and the Weisenthal Cancer Group. The study was a meta-analyses that examined the sensitivity and specificity of human tumor primary culture studies and the efficacy of drug therapies selected, based on laboratory findings. In aggregate there were 28 retrospective and 15 prospective trials included.

The overall sensitivity was 0.92 (95 percent C.I. 0.89 – 0.95), and specificity of 0.72 (95 percent C.I. 0.67 – 0.77) with an area under the curve for the ROC of 0.893 (SE = 0.023, p < 0.001). When clinical outcomes were examined, it revealed a two-fold improvement for assay-guided therapy for standard of care (odds ratio 2.04, 95 percent C.I. 1.62 – 2.57, p <  0.001). Finally, the one-year survival rate for assay-guided therapy proved superior (OR 1.44, 95% C.I. 1.06 – 1.95, p= 0.02).

As can be seen from this well conducted meta-analysis, there is a wealth of evidence to support the use of human tumor primary cultures for the selection of chemotherapy.

Empowering Patients Towards Personalized Cancer Care

We have one more guest blogger to introduce during Dr. Nagourney’s absence: Patricia Merwin. Pat just celebrated her fourth anniversary of wellness after receiving a diagnosis of metastatic lung cancer.

In July of 2011, I attended a local TEDx conference in Long Beach, CA where Dr. Robert Nagourney gave a compelling talk about the nature of his work and the future of cancer care. TED is a global organization with a mission to “share ideas worth spreading,” a very appropriate forum for Dr. Nagourney to share his insights into cancer and how to defeat it.

Just three months earlier, at another TEDx event in the Netherlands, Dave deBronkart also gave a talk about the future of cancer care.  Dave deBronkart, better known as “E-patient Dave,” was diagnosed in January 2007 with a rare and terminal kidney cancer.  Given a dismal prognosis, Dave refused to cede his life to “standard care.”  Instead, he turned to a group of fellow patients online and found the information that eventually led to a treatment that saved his life. Dave deBronkart has since become a prolific online patient advocate and an internationally renowned speaker on the subject of patient empowerment and participatory medicine.

Like e-Patient Dave, I was given a “dismal prognosis” when I was diagnosed in 2008 with advanced metastatic lung cancer.  I too refused to cede my life to the standard protocol of the day. But it was not my health care providers who led me to Dr. Nagourney, it was a close friend.  Empowered with the knowledge that it was possible to improve my odds for survival, I chose functional profile testing (EVA-PCD®) to help determine my personalized treatment plan. It was a wise, informed decision resulting in the best possible outcome.  I have since become an online patient advocate, spreading the word to thousands of other patients so that they can become knowledgeable about this important test that could save their lives.

According to Dr. Nagourney, “Every system performs exactly as it was designed to perform. The current system of medical oncology provides adequate care for the average patient. There is little room for true, individualized care, for it disrupts the norm.”  But every patient with cancer has the same objective. To find the treatment that will work for “me.”  With a system skewed toward averages and away from the individual, the path to personalized medicine must be to empower the person with the most at stake – the patient. Dr. Nagourney says, “Today’s patient must become his or her own best advocate.”

More and more, patients are turning to online forums and other patient groups, not just for support, but to seek and share the latest news and information about treatments, side effects, tests, etc. If two heads are better than one, then thousands of engaged patients should, at the very least, provide good food for thought, “ideas worth spreading.”

Dr. Nagourney believes that “it’s in the online trenches where the real, personal war of cancer is being waged.  The old paradigm, that knowledge runs downhill from academics to practitioners to patients is being turned upside down as empowerment goes from the bottom up, not just from the top down.”  I’m sure e-Patient Dave would agree, along with countless other e-patients like him.

Cancer Treatment – A Husband’s View

Gary Brutsch

Guest blogger – Gary Brutsch

Dr. Nagourney is currently attending an international conference where he is an invited speaker. During his absence we will have guest bloggers sharing their views on chemosensitivity testing and the EVA-PCD® assay. Our first guest is Gary Brustch.

Five years ago, my wife of otherwise good health was diagnosed with Stage IV uterine cancer. Following a surgical “solution,” we commenced our search for the next best alternative to just waiting for the disease to take its course.

We settled on a protocol supervised by a major cancer treatment center in Texas. For a total of six months, my wife, Tina, was treated with a combination of chemotherapies. During this treatment we continued to look for medical care that was more scientific-based.

At the conclusion of their protocol, we were notified that the course of treatment had not been successful. At this time Tina’s cancer marker numbers were approaching 800. Two days after this notification we decided that our final option was to contact Robert Nagourney, MD, at Rational Therapeutics in Long Beach, CA.

Our decision was based on the belief that his tumor sensitivity based chemo architecture was probably a more effective method to treat her tumor growth.

After obtaining a tumor sample from Tina and subjecting it to a laboratory process (assay testing), Dr. Nagourney prescribed a specific chemotherapy cocktail for her treatment. After one month of supervised treatment, Tina’s cancer marker number was under one hundred.

We are now into our fourth year of maintenance supervised by Dr. Nagourney. Our united opinion seems to say that, as health challenged individuals we must demand that caregivers treat our health challenges on a focused, individual basis.

We cannot accept that one category of chemotherapy is good for all.

No One is More Interested in Curing Your Cancer Than You

A diagnosis of cancer thrusts a, heretofore, healthy individual into the strange and unfamiliar territory of medical oncology. Many of my patients describe this transition as “entering the cancer bubble.” Suddenly, you are on the inside and everyone on the outside is talking at you about what to do, where to go, whom to see, and what treatments to receive.

From the inside of the bubble however, all of this has a hollow ring as you ponder many options, few good and some, positively frightening. Unfortunately, few patients have the time to complete a MD, or PhD, between diagnosis and the initiation of treatment. Lacking the requisite expertise, they turn to the “authorities” for advice.

Depending on which “authority” one consults, the recommendations may be colored by prejudices and biases. Some physicians adhere strictly to the National Comprehensive Cancer Network guidelines. Others insist upon accrual to Cooperative Group and Phase II trials. University-based investigators will often recommend developmental studies. And some physicians will follow the path of least resistance, examining such issues as cost, chair time and reimbursement, before considering what treatment to deliver.

It is in this milieu, that patients find themselves adrift. Who exactly should you trust? What is their motivation? To put it crassly, when they recommend a specific treatment, what’s in it for them: Cooperative Group points (provided to the most active accruers), academic accolades (the currency of junior faculty), cost containment (the purview of the managed care physicians), or finally, profit margins? Yes, there are a small number of physicians whose choices reflect their own pecuniary interests.

The antidote to all this uncertainty lies within each patient; answers to vexing questions crying out to be heard. These answers reflect the biologic features of each individual’s tumor. What pathway, what repair mechanism, what survival signal drives your tumor? No one has a perfect answer, not the genomic investigators (despite their protestations to the contrary), nor the immunohistochemists, despite the significant appeal of the platform. And not the immunologist (despite brilliant progress in this field over recent years). The closest approximation to human tumor biology is, well, human tumor biology. Using cellular constructs, in the form of native state microspheroids, we can today approximate the response profiles of patients undergoing systemic therapies. Using systems approaches to complex questions, the multitude of factors that contribute to objective response can be examined and elucidated.

No test is perfect. No patient is guaranteed a good outcome. Yet, doubling the objective response rate, and as we and others have documented, improving the time to progression and overall survival can be achieved with available methodologies that apply functional profiling to individual tumors.

No one would walk away from an investment formula that doubled the value of their portfolio. Few would turn down the opportunity to enhance their real estate positions predicated on reliable information from a realtor. Yet everyday, physicians convince patients to walk away from available, published, established methods that can improve response rates, diminish toxicities and avoid futile care. In this environment it is critical for patients to take charge of their own cancer management. Patients must not be dissuaded from seeking the best possible outcomes. Physicians, no matter how well intentioned, are human. Their opinions can be colored by misconceptions and an incomplete understanding of the questions at hand. Laboratory analysis empowers patients to make smart decisions.

In the game of cancer we need all the help we can get. After all, no one is more interested in saving your life than you.