The Death of Christopher Hitchens

Among the more colorful writers, orators and pundits in the later part of the 20th Century and the early part of the 21st was Christopher Hitchens. Born in England in 1949, he moved to the United States where he became famous for his deeply held political views. An outspoken critic of injustice, he called it as he saw it. While his political leanings were mostly liberal, he was willing to take on the establishment on both sides of the political isle when he saw injustice and political hypocrisy.

Christopher Hitches died at age 62 from cancer of the esophagus. Although unapologetic for his use of alcoholic beverages and tobacco products, his lifestyle may have contributed to his diagnosis. What saddens me most is the possibility that he could have done better. And didn’t.

Like so many celebrities when they are diagnosed with cancer, Hitchens entered a realm that I call, “social medicine.” Not to be confused with socialized medicine and related political issues, social medicine is the process whereby the rich and famous receive care from the “right” doctors. These luminaries, through their channels and connections, are hand carried to the most famous physicians in the country. Their prominent and widely published ivory tower investigators then provide the best care money can buy. Yet, more often than not it is exactly the same therapy that they would have received from their home-town oncologists, who read the same journals, attend the same meetings and adhere to the same NCCN guidelines as the “best and the brightest” academics. We then conveniently chalk these patient’s failures up to the biology of the disease and the patient’s drug resistance rather than examining the more discomforting reality that protocol therapy doesn’t work for famous patients any better than it does is for anyone else.

But what if these patients just got the wrong treatment? What if the drugs these doctors chose were the very best for many, but not right for them? What if the right treatment was just right around the corner, but these prominent academics couldn’t see it? What if these patients had submitted a tumor sample for an EVA-PCD® assay and knew which drug or combinations would kill their cancer cells?

It isn’t that Christopher Hitchens or Steven Jobs are more important than any other patient. Their collective suffering and the losses to their families are no greater than any other cancer patient who confronts this illness. It’s just that they are famous and we know about it from the beginning to the end. We watch as these patients suffer through the toxicities and side effects of randomly administered therapies. And, in the case of Hitchens we are provided a blow-by-blow description in his writings. Unlike other patients who seek their care outside of the limelight, these celebrities are above the fray, protected by their handlers, PR agents and managers – they are unapproachable. With Jobs or Hitchens I would have relished the opportunity to offer any assistance possible, and through contacts at Apple I actually tried, but to no avail.

These individuals suffer and die in the public eye. Like salt in a wound, investigators like my colleagues and myself who are engaged in the pursuit of better, more intelligently delivered therapies, suffer with them. No, they are not more important, but it just seems so when you watch it every day on television, online, or in the print media, you clearly see an “in your face” example of a failing paradigm of cancer therapeutics.

Breast Cancer and Avastin, the Ongoing Saga

As many are now aware, in November of 2011, the United States FDA withdrew approval for bevacizumab (Avastin) for the treatment of breast cancer. Medicare and the National Comprehensive Cancer Network  (NCCN) are now re-examining their guidelines. In the interim, reimbursement for Avastin is a patchwork of approvals and denials across the country.

Into this mix comes an interesting concept apparently floated by Roche’s European affiliates. Described in a brief press release was the suggestion that Roche might be prepared to attach Avastin reimbursement to its efficacy. That is – Roche would only demand payment from patients and third party payers if the treated patient revealed objective evidence of response. This is an interesting idea!

The concept of conditional reimbursement is extremely intriguing. Contrary to contemporary reimbursement policy, the purveyors of therapy would only receive compensation if they could prove benefit, not mind you, benefit in the broad brush Phase III tiny statistically significant result (e.g. the FDA approval of erlotinib plus gemcitabine in pancreatic cancer for a median survival advantage of 10.6 days!), but instead very real benefit on a patient-by-patient basis.

We use erlotinib plus gemcitabine, as well as Avastin combinations, to great benefit for many of our patients and applaud the availability of these drugs and combinations. But we never, just give them. Were the federal government, major payers or HMOs to be prepared to reimburse novel therapies predicated on their efficacy, we might envisage a meaningful advance in cancer therapeutics.

Today, few small laboratories, start-up companies and early stage biotech firms have the resources to marshal multi-million dollar clinical trials to test new therapies. This may in part be why advances in cancer therapy are moving so slowly forward.  The barriers to entry are insurmountable, causing many good ideas to fall by the wayside for lack of the hundreds of millions of dollars required to achieve FDA approval and Medicare reimbursement. But what if on an individual basis, reimbursement policies reflected the most meaningful of all endpoints – individual patient response and survival. Even the largest pharmaceutical companies are now coming to realize that despite their clout they too are suffering under the guidelines forced upon drug developers in this era of ever increasing regulation.

This is a concept worth pursuing. Let’s see where it goes.

Thank You

I would like to take the time to thank everyone who responded to my last blog entry about the passing of my father. His memorial service is this Sunday.

Perhaps next week, I will be better able to focus my attention to communicating, via this blog, about medical matters.

Cancer Gets Personal

Early in the morning of Nov 21, I suffered the loss of my father. However prepared one might be for this eventuality, there is nothing that can really prepare you.

At 95 years of age, he had lived longer than many. I had cared for my father as a patient since 1974, when he was first diagnosed with inoperable prostate cancer. I remember the day I received notification of the diagnosis. I felt a sense of deep sorrow that my father at 74 would soon die of high-grade locally advanced prostate carcinoma. As a member of the generation that forgot to have children, I was saddened that my father would not live to see grandchildren.

I remember traveling to Connecticut for his initial evaluation and then scouring the literature for the best possible options. Fortunately, despite the aggressiveness of the disease it had not metastasized.

I arranged for my father to travel to California where I then oversaw his care in collaboration with Dr. A.M. Nisar Syed in radiation oncology. There is a well-known dictum in medicine that only doctors and their families suffer unexpected complications. In my father’s case it certainly rang true. First, the radiation implants did not penetrate the tumor and needed to be removed and replaced. As a result of this double procedure, he then developed bleeding that required emergency hospitalization several days later.

Despite these hiccups, the combination of implant and external beam radiation provided excellent control. With a full recovery my father returned to his normal activities.

As so often happens in medicine a personal experience provides a focused interest. I delved into the prostate cancer literature and became increasingly interested in the biology of this disease. One area of particular interest was the role of hormonal therapy. When? How much? How long?

When my father’s PSA began to rise the second year, I had a unique opportunity to examine these questions at a very personal level. Would the early institution of androgen blockade induce the hormone refractory state? Was there a “trigger” value of the PSA that dictated the institution of the therapy? I remember discussing these questions with a prostate cancer expert and chairman of the ECOG committee, Dr. Basil Kasimis, whom I had had the pleasure of working with several years earlier. I agonized over starting hormonal therapy as my father’s PSA rose from 4 to 10, to 25, to 54, and up to 150. Despite these frightening PSA values, there was no evidence of metastatic disease on serial bone scans, which I performed religiously every six to 12 months.

Almost a decade passed but there was still no metastatic disease. And then my father developed severe coronary artery disease in his early 80s. Coronary artery bypass graft was the only option. To avoid the possibility of seeding the sternal wound, I bit the bullet and treated him with hormonal suppression – immediately driving the PSA to nearly 0.

With his coronary artery bypass surgery a success, he came off hormonal therapy and I let his PSA drift upward again.

As he had returned to Connecticut, his urologist became increasingly concerned by the rising PSA, and, without my knowledge, decided to rechallenge him with hormonal ablation. While I understood the motivation for this intervention, I didn’t agree and took him off all hormones for a prolonged period of time. Over the subsequent years, I would intervene occasionally to shepherd my father through pneumonia, a broken hip, a bleeding ulcer, and a variety of other maladies so common in patients who transition from their 80s to their 90s. On several occasions, we gave brief courses of hormonal ablation to suppress the PSA, when the steepness of the rise gave concern. Twenty-one years after his diagnosis my father died of natural causes, with no evidence of metastatic prostate cancer.

The experience was instructive on many levels. First, I realized how important it is to treat all patients as if they are a member of your own family. Second, it takes a lot of guts to step outside the normal guidelines and to do what you believe to be best. Third, I realize that in medical oncology it is the most “aggressive” physician who has the courage not to treat.

So often in this field doctors institute treatment, not because it is needed, nor because it will work, but because by doing so they have “done their job,” the rest is no longer their responsibility.

But “doing your job” as a physician, particularly in medical oncology may demand that you step outside of the NCCN guidelines, however uncomfortable it may make you, to do the right thing. Virtually every urologist or oncologist in America would have treated my father for his rising PSA 20 years ago. While I cannot say with certainty, I feel fairly confident that he lived the past 21 years in part because I didn’t treat him. Every patient needs an advocate. I feel a sense of personal satisfaction that I was there to be my father’s. He lived a long and productive life, I hope and believe that I helped him to do so.

Every experience, even traumatic ones, can have a silver lining. My father’s diagnosis lead me to develop a combined modality approach for locally advanced prostate cancer that has provided among the best biochemical relapse-free survival rates ever observed in this disease. Had I known then what I know today, I would have certainly treated my father with this approach.

Secondly, my interest in prostate cancer lead me to examine the lifestyle, nutritional, and micro-nutritional aspects of this disease – knowledge that I apply to this day. This lead to my analysis of an herbal remedy for prostate cancer that unfortunately uncovered the adulteration of an herbal mixture as we reported. (Herbal Composition PC-SPES for Management of Prostate Cancer: Identification of Active Principles: Journal of National Center Institute, Vol. 94, No. 17, September 4, 2002.) Despite our disappointment at the discovery, it lead me to reexamine the use of estrogenic substances as therapies in this disease, insights that have provided benefit to many of my patients ever since.

In retrospect, it may have been my father’s natural inquisitiveness (that he imparted to me) that leads to my pursuit of these lines of investigation. And for that I will always be grateful.

To read more about Alphonse Nagourney, click here.