Rumination 16: Bad News, Good News

Rumination 16. Bad News, Good News

By

Thomas P. Vogl

September 10, 2008

I’ll dispose of the bad news first. My scans on 8/26 showed definite disease progression, particularly in the liver. Let me hasten to add that my liver function tests are still normal and my liver is not enlarged. So, I have been kicked off the trial, which is probably a good thing since it is statistically unlikely that it was doing me much good. I had very positive conversations with both Dr. Shapiro and Dr. Hodi and we agreed that there are two ongoing studies that make sense for me. One is Dr. Hodi’s  ongoing trial of our old friend MDX-010 (aka Ipilimumab) which is now available without the addition of dacabazine and is a CTLA-4 immune system enhancer. The other is a trial of a cyclin-dependent kinase inhibitor, Cdk-inhibitor, run by Dr. Shapiro, one of a new class of drugs that, at least theoretically, has a great deal of promise and has had success with melanoma in early trials. I wrote to both Dr. Shapiro and Dr. Hoi that my preference is to participate in the Cdk-inhibitor trial first, since we would find out whether it is working in six to twelve weeks whereas it will take 20 weeks or longer to see if Ipi is effective on me. It has done wonders for two friends of mine with metastatic melanoma. (I wrote most of this Rumination on 8/29 at which time I did not know which trial it will be. I must admit that the uncertainty was seriously discomforting and an e-mail from an amazing guy, Andrew Wolanski, Dr. Shapiro’s nurse practitioner and right hand man, was remarkably reassuring and calming.)

In the process of deciding on possible studies, I ran across a review paper on Cdk inhibitors [I. M. Chu et al, The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anti-cancer therapy, Nature Reviews, Cancer 8: 253-267 (April 2008)]. Looking at this paper reminded me why immunology and intracellular signaling pathways have always made my head spin and made me wonder whether I am sorry never to have paid much attention to those subjects or whether I am glad I didn’t.

{Added September 9: On September 8 I was told that I would be accepted into the Cdk inhibitor trial. SCH727965 is a novel pyrazolo[1,5-a]pyrimidine which potently and selectively inhibits the cyclin- dependent kinases CDK1, CDK2, CDK5 and CDK9. The most common treatment-emergent adverse events are nausea/vomiting, diarrhea, neutropenia, and fatigue.  However, SCH 727965 is rapidly eliminated with a terminal half-life of 1.5 to 3 hours, so that recovery from side effects is rapid. A good response has been observed in other melanoma patients in the study. I expect to start the study next week.}

The good news is that, at long last, someone has had the courage to announce that, as far as clinical trials of cancer drugs is concerned, the emperor is hardly wearing any clothes. M.K.B. Pamar et al, from the MRC Clinical trials Unit in London, UK, wrote ‘Speeding Up the Evaluation of New Agents in Cancer, J.N.C.I. 100: 1204-1214 ( September 3, 2008) available on-line as DOI: 10.1093/jnci/djn267. The abstract reads:

Despite both the increase in basic biologic knowledge and the fact that many new agents have reached various stages of development during the last 10 years, the number of new treatments that have been approved for patients has not increased as expected. We propose the multi-arm, multi-stage trial design as a way to evaluate treatments faster and more efficiently than current standard trial designs. By using intermediate outcomes and testing a number of new agents (and combinations) simultaneously, the new design requires fewer patients. Three trials using this methodology are presented.

Hurray for our side!

While I am at it, I might as well get another pet peeve off my chest. What is it about cancer that makes people talk in terms of ‘cancer survivor’ and battles and courage. We never hear of people ‘surviving’ COPD, or heart disease, or strokes, or AIDS if they live with the disease for more than a couple of years. Nor have I ever read ‘She died after a long, heroic struggle with multiple heart attacks’. Middle ear infections in children (that can lead to brain damage or death) often re-occur; when have you heard anyone say “My Johnny is a middle ear infection survivor”? Cancer is a disease like any other, sometimes fatal, sometimes not. It can re-occur. It is true that two generations ago, cancer was a mystery and its cause unknown. It was commonly undetected until symptoms appeared by which time the patient was terminal. I remember a time when even physicians would not say the word, but use ‘CA’ as a euphemism. People, its 60 years later – we know what causes cancer. Can we please stop the bullshit! I cannot say it better than Colleen Shaddox, a writer in Hamden Conn. did in the Washington Post on June 2, 2007 (page A13):

It's Cancer, Not a Moral Crucible

"You're so brave," people would say. "You're a real hero."

I used to get that a lot after my hair fell out. The effects of chemotherapy made me look like some plucky child protagonist in a movie of the week. Volunteering to have cancer to spare someone else the pain of it would have been heroic. But I was no volunteer.

"I'm not brave," I would say, "I'm just unlucky."

This made people uncomfortable. But I would rather do that than accept unearned praise or, worse, listen to comments that, to me, dishonor those who have died of cancer.

During the 10 years I've been a cancer survivor, my marriage has grown stronger, my bouncing baby has blossomed into a gorgeous virtuoso of sarcasm, and my career has taken flight. I am grateful for this life every day.

It's tough being a cancer patient. Surgery, chemotherapy, radiation and the prospect of painful, premature death are quite enough for one person to shoulder. The additional burden of sainthood is simply too much.

When strangers would observe bald little me doing something normal -- grocery shopping, for example -- they would beam like proud parents. "You are so brave!" they would exclaim.

Of course, grocery shopping is a necessary act, even for people with cancer, and not terribly dangerous. But my admirers persisted, as though I were suddenly extraordinary. "I could never be as brave as you!"

That oft-repeated line is telling. After all, if cancer is a disease for extraordinary people, the average Joe or Jane doesn't have to worry. Even in the psyches of the healthy, fear of cancer is enormous. Consciously or not, making cancer patients the saintly "other" helps make that fear manageable.

When I battled breast cancer, I was frequently told that God would not take a person as good and loving as I. It might be a nice thing to believe: I was a churchgoer. I'd worked in a soup kitchen, collected for Toys for Tots. I was not Mother Teresa, but then virtue doesn't make one immortal; Mother Teresa died, just like everyone else.

When I expressed skepticism that my character could supercharge my immune system, I was often treated to impromptu sermons about keeping a positive attitude. Consider the logic: When you have the flu, people say, "I'm sorry. Hope you feel better." When you have cancer, people expect you to maintain a positive outlook and remember that you'll come out on top. People I barely knew would quote lines such as Bernie Siegel's "There are no incurable diseases, only incurable people."

Ultimately, stressing the importance of positive thinking is a way of managing fear. It makes cancer controllable -- for the patients, yes, but especially for the healthy. But linking virtue, resilience and survival dishonors those who do not survive.

I remember watching a television segment on an athlete who'd had cancer. "Cancer really picked on the wrong person," one of those interviewed said in explaining the man's determination and ultimate recovery. So, are there right people for cancer to pick on?

I kept my sanity during treatment through the help of a support group. Half of these women have died. Those who did not make it had cancers with high mortality rates or cancers that were quite advanced when they were detected. The women were strong, smart and caring -- such terrific ladies that they almost made me believe the myth of cancer sainthood. But they also got parking tickets and forgot appointments, just like everybody else. They were human, and I loved them for it.

My friends were failed by their cells, not by their will. The horror of cancer is that it descends on irreplaceable mothers, brothers, children and friends. Some of them will die, no matter what we or they do. As we strive to honor those who had and those who are still fighting the disease, it's important to remember whom exactly our words are meant to comfort -- the people speaking, or the people in need of support.

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I also want to recommend an exceptionally readable book, that both of us enjoyed reading, by Meredith Norton, ‘Lopsided. How having breast cancer can be really distracting. A memoir.”  Viking Press, ISBN 978-0-670-01928-1 (2008). Available from Amazon at

http://www.amazon.com/Lopsided-Having-Breast-Cancer-Distracting/dp/0670019283/ref=pd_bbs_sr_1?ie=UTF8&s=books&qid=1220102157&sr=1-1

or

http://tinyurl.com/6mx4xe