Cancer Patients: Cure the Curable, Treat the Treatable and Avoid Futile Care

During my interview with Jeff Michaels on the March 28, 5:00 P.M. Fox News, we explored the themes of my current book, Outliving Cancer. One of the points that most interested my interviewer was the appropriate use of our laboratory platform for the selection of therapy. He asked, “Are there some patients for whom there is no cure?” I responded by explaining what it is, that our laboratory test is designed to do: “Cure the curable, treat the treatable, and avoid futile care.” Jeff Michaels stopped me and asked that I might repeat what I had just said. It seemed that my succinct description resonated.

However simple this distillation of our work may seem, I realized it was actually rather profound. After all, we are confronting an escalating crisis in medicine. How do we meet the needs of a growing population of cancer patients with shrinking resources? How do we allocate treatments to those most likely to respond and finally, how do we avoid the misadventures of toxic and ineffective therapies for those destined to fail chemotherapeutic intervention? On every level, laboratory models can assist us. For those patients with early stage breast cancer, ovarian cancer, small cell lung cancer, non-Hodgkin lymphoma and many leukemias, the expectation of a cure is well within our reach. These patients must receive the very best treatments from the start.

The larger population of patients we confront are those with diseases like gastric, colon, non-small cell lung, recurrent breast, recurrent ovarian or sarcoma for whom cures are less likely and effective therapies must be tolerable so that they can provide benefit without undue toxicity. These are the patients for whom cancer can become a “chronic disease.”

Finally, we must all confront patients for whom treatments offer little likelihood of benefit, yet significant risks of toxicity. These heavily pretreated patients, or those who present with refractory malignancies like pancreatic, kidney cancer or melanoma – represent a special subset. Here the role of the physician is to decide that almost Shakespearean question, “To treat or not to treat.”

This is a particularly delicate circumstance as it forces the doctor, the patient and the family to confront the most difficult question of all, “Am I dying?” The answer is “maybe.” Without seeming flip, every patient no matter what diagnosis, has some chance of response to therapy. If we examine the performance characteristic of our laboratory analyses, they consistently double response rates. With this group however a doubling of response rate may still provide a rather low likelihood of meaningful benefit. If the laboratory finds drug resistance in this group, it is a near certainty that the patient will not respond.

However distressing this data may be, it may be comforting to know that the patient has left no stone unturned. For those patients where a treatment appears active, despite their diagnosis or treatment history, then the discussion surrounding tolerance, toxicity and realistic likelihood of benefit can be undertaken intelligently. This is the embodiment of rational therapeutics.

Renal Cancer Patient Update

A few weeks ago, I discussed the case of a patient with metastatic renal cell carcinoma who upon arrival in my office for a consultation, appeared to be too ill to even consider further treatment. Determined to persevere, he provided us with a sample to test and underwent our suggested regimen. As was mentioned previously, the patient was delighted with his response and has now returned to many normal activities, including working out at the gym.

What I did not expect was to receive a letter a few weeks later from his treating oncologist in Northern California. He was thrilled with the patient’s “massive” response, even commenting that the carcinoma had reacted more like a lymphoma than the typically aggressive and non-responsive renal cancer. In fact, the patient is doing so well he is being considered for a kidney removal (a procedure that he couldn’t have possible survived just weeks earlier).

Working in tandem with treating physicians is a partnership that benefits patients. It is exhilarating for myself and my team to hear about such favorable outcomes.

Are New Cancer Drugs Always Better?

Few cancers instill a greater sense of fear in the medical oncologist that metastatic renal cell carcinoma, the most common form of which is known as clear cell cancer. This type of kidney cancer — driven by a mutation in a gene know as VHL — spreads rapidly, metastasizes to almost any and all organs and historically responded to almost no therapies. The development of Interleukin-2 (IL-2) in the 1980s offered a glimmer of hope. Yet, even this breakthrough ultimately yielded complete and durable responses in a mere 10 percent of patients.

By focusing on the hyper-vascular nature of this disease, investigators then developed a second line of defense that attacked the blood supply of these cancers. Following the introduction of Avastin, a number of small molecule VEGF inhibitors were introduced. Most recently, a class of drugs known as mTOR inhibitors gained popularity by providing objective responses and showing evidence of improved survival.

But what happens when all the really “hot new drugs” fail to provide benefit?

This was a question I confronted in a charming, 68-year-old neurologist who traveled to visit me from Stanford University where he received highly appropriate, yet unfortunately ineffective therapy. The patient presented in July 2010 with rapidly progressive kidney cancer that had overtaken his lungs. He was started on oral Sutent (the treatment of choice). His management was complicated by a hemolytic anemia. When I met the patient in October, I was concerned that he could not survive long enough to take on another treatment, no matter how effective it might ultimately prove to be.

As a physician, he beseeched me to study his tumor in the hope of finding any therapy to salvage him from his rapidly deteriorating course. A small biopsy was obtained with the help of one of our surgical colleagues. The results were striking — no evidence of activity for sorafenib, sunitinib (Sutent), nor the Rapalogs (Rapamycin derivatives). In one fell swoop, all of the newest therapies were swept aside with little likelihood of benefit. Despite the established literature, this patient was clearly sensitive to chemotherapeutics. It was evident to me that the treatment outline, a combination of three drugs, could provide meaningful clinical benefit if the patient could tolerate even the most modest associated side effects. With the kind cooperation of the treating physician in Northern California, our recipe was followed to a T.

The treating oncologist pulled no punches in his description of this patient’s prognosis. Nonetheless, he kindly assisted in the management of the treatment we described. While the cancer-related hemolytic anemia raged, and the patient fought for air, the treatments were delivered. Too ill to leave the hospital, his entire first course of therapy was delivered on an inpatient basis.

For several weeks, we anticipated the worst. And then, a phone call from a chipper-sounding patient. Breathing comfortable, his chest x-ray had cleared, his anemia had resolved and he was being readied for discharge. A short time later, an abdominal ultrasound revealed measurable improvement in the kidney cancer, further confirming objective response.

The patient, now home, could not be happier. The excellent outcome is as gratifying as it is unexpected. There is no question that no one else would have given this treatment. And there is further no question that the patient would not be alive today had he not received it. There are many lessons to be learned from this experience. Among them, that every patient deserves the opportunity to get better; that laboratory analyses can identify unexpected options for patients, even with the worst malignancies; that new drugs aren’t always better drugs; and finally, that nothing succeeds like success.