There’s a feature article in this week’s Newsweek that discusses the limitations of what we’ve achieved in the “War on Cancer” waged by Richard Nixon more than three decades ago.  Unlike the vast, vast majority of cookie-cutter, feel-good stories about the miracles of science and all of the progress we’re making, this extensive article covers the unfortunate reality that our progress has been soberingly modest.   Unfortunately, this is a necessary reality check, and it highlights several of the problems with our current system of cancer research.

   One of the biggest issues is the presumption that if we raise money for cancer research, we’ll cure it.  It’s not that progress can’t be made, but the goal of curing all forms of cancer, a disease in which new cells mutate faster than we can develop new treatments to address the new challeges they create, is right up there with the goal of teleporting across time and space.  I’ve rarely heard an experienced oncologist talk about the feasibility of actually curing most cancers (Nobel laureate James Watson said in 1998 that Judah Folkman’s work on anti-angiogenesis would cure lung cancer in two years: I remember then thinking that this was an irresponsibly dumb utterance from a presumably smart person, and history will show he was quite wrong).  Some that are genetically pretty simple, such as chronic myelogenous leukemia (CML), have been amenable to some impressive breakthroughs, but ones like pancreatic cancer and lung cancer have been a much harder nut to crack.  It’s not for lack of trying.

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Today’s NY Times included a high profile article about the difficult balance between the clinical value of some expensive cancer therapies and their financial value. I think it did a fair job of portraying both sides of the issue — that therapies like avastin, erbitux, and others are certainly priced aggressively for the modest but generally convincing benefits they provide, leaving some people wondering whether they have enough impact in a non-curative setting to justify the rather high costs. Contrasting this with inexpensive medicines (such as if an off-patent chemo were found to be modestly helpful) or expensive medicines that can be expensive but seem convincingly justified by the striking benefits (such as gleevec for chronic myelogenous leukemia, or CML), the authors offer that the costs to the patient personally can be daunting if they are paying 20% of what amounts to thousands of dollars per year, and of course also the costs to society. While countries with single-payer medical care, ranging from Canada to the UK to many/most other parts of the world, have faced questions of whether expensive cancer drugs that don’t increase the cure rate are “worth it”, the US system has not had to face much means-testing.

But with costs of cancer treatments rising rapidly, and with many competing needs, such questions are creeping into US-based discussions more and more. In the commentary about the plenary presentation of the FLEX trial that demonstrated a modest but statistically significant survival benefit in advanced NSCLC, Dr. Tom Lynch from Massachusetts General Hospital was charged with the task of providing some context about whether the 1.2 month survival benefit could justify the anticipated costs.

I think we’re going to be facing more and more of these hard questions, ones for which I don’t have any good answers. As the article notes, through the words of one of the quoted physicians (Dr. Eric Winer, a breast cancer specialist at the Dana Farber Cancer Institute in Boston), we may conclude that the cost-benefit (now financial as much or more than our usual mindset of weighing risks of side effects and quality of life issues vs. improved response rate and survival) is not favorable for society as a whole, but you have a different perspective when you have a patient looking for options in front of you.

I wonder whether the cost of things like co-payments that may run into thousands of dollars is now a factor for patients and their families. I certainly hear patients and families express a desire to explore “anything, regardless of the cost”, but is this really something that just doesn’t or shouldn’t enter into the picture? I can understand a “go for broke” (literally) approach much more in a curative setting, for which we really haven’t seen much controversy. But would people be willing to have their families go into debt for a non-curative treatment that would be expected to extend survival by 2-3 months? Is it more the hope that a person will be one of the major beneficiaries that gets many months or even years of benefit, and it’s not possible to put a price tag on hope?

These aren’t pointed questions for which I have a presumed answer. I can’t say how I’d feel if it were my father or wife or closest friend facing cancer. But I’m interested in hearing from people who face advanced cancer themselves or in someone very close to them, “is there such a thing as a cancer treatment not being worth it financially?”.

This doesn’t directly relate to lung cancer, but in a prior post I described a trial of the vitamin D analog calcitriol (Asentar) with taxotere for treating advanced NSCLC. Although it has been very unclear whether there might be any future for this agent in lung cancer, I and many others were pretty impressed by the results of a randomized phase II trial for metastatic prostate cancer, called ASCENT, with 250 patients who were randomized to taxotere and prednisone with or without calcitriol. This study actually showed an improvement in overall survival in the recipients of calcitriol with chemo, but it wasn’t a huge trial. A larger phase III randomized study with the same design (called ASCENT-2, cleverly enough) has been ongoing in prostate cancer. Presumably, if this one came out as well, it would look good for it to be approved by FDA.

While we don’t have any real results yet, we know from a press release that the trial was stopped early due to an unexpected excess of deaths on the arm that received calcitriol with chemo. This led the Data Safety Monitoring Board to close the trial. This doesn’t have any immediate implications for lung cancer, except that now I’d really doubt we’ll see the concept I described in my post followed with a larger study in lung cancer. And it’s another example of how an early small trial can look really promising, but the new treatment not only be of no significant benefit but also potentially be harmful. I haven’t been recommending high dose vitamin D for my patients, but it’s a cautionary point that there might be detrimental effects from high doses of certain vitamins (potentially from the interaction with chemo but wouldn’t occur without concurrent chemo). I don’t have any more details, but I’ll let you know if we learn more.