by Azra Raza
Some fortunate individuals with cancer survive to tell their stories. In this book, a few of my patients agreed to do precisely that. Their humanity is on full display in their fierce desire to live, to celebrate life, even as they face life-threatening illnesses. Almost all of them rejected anonymity. Instead of signing their stories with a soup of alphabets or case numbers, they chose to provide their real names, even their pictures. They want to be identified. They want you to know they are living, breathing individuals. They want their voices heard. They walk you through their private hells, but then they also share with you their Joycean spirit: “To live, to err, to fall, to triumph, to re-create life out of life.” Above all, it is their palpable desire to live just a little longer at all costs that leaps from the pages. They are the reason why we, the oncologists, obsessively, zealously, fanatically, pursue implausible treatment options—exploring wild possibilities, not giving up, not letting them give up. They provide the helium for our sagging spirits.
Many more, however, have died. When the decisions and actions that lead up to those deaths are not reexamined carefully, questioned, challenged, the indifference—our silence—kills patients again and again. My role in this examination shifts across multiple dimensions. I am variously a treating oncologist; a wife and then a cancer widow; a friend; an observer; a remote consultant; a basic scientist; a clinical researcher. I question the recommendations of experts, the choices that families made. I marvel at the innocence and hopefulness of the patients as they agonized their way through one excruciating experimental trial after another. Above all, I question my own decisions. Were they based on hard facts, or were they uncomfortable choices based on inadequate data derived from incompetently designed studies? If I could not provide a better life to my patients, could I have provided a better death? Can I improve upon my communication finesse? How do I acquire the skills missing from my tool kit for interacting more compassionately with my patients at a deeper human level? Isn’t that why I became a doctor in the first place? Candid discourse humanizes both the patients and their oncologists. The aim is to proffer new ideas, make all of us rethink, question ourselves, challenge norms, and take a hard look at our rigid systems, our medieval institutions, through the prism of profoundly human issues affecting patients, families, survivors, oncologists, basic researchers.
Ultimately, I ask, if any of those involved—friends, families, patients, doctors—were to cast a backward glance, knowing what they know now, having had time to think, digest, and live with the loss, what decisions would they alter? A clear picture can only emerge with retrospection, recalling snippets of conversation, nagging details, hopeless choices. The sharp vision, the clairvoyance of grief, present from the first moment but suppressed, trickles into consciousness gradually. Honesty finally becomes possible on both sides as talking to families years later allows me to give my candid interpretation because they are finally ready to hear it. The process of retrospection forces us to relive the trauma, awaken repressed memories. The goal is not to revel in suffering but to liberate us from the past, prepare us to do better in the future.
As long as there is a single Henry W. dying a swift, brutal death, there can be no disagreement about whether great or little progress has occurred in cancer research and treatment. Let us, first and foremost, accept with all humility that our job remains unfinished. I would go further and say, let us accept that the traditional ways of doing most things are sclerotic. My insistent focus on the granularity of individual pain and suffering in the pages that follow is to highlight the urgent need for change, to force us, as individuals and as a society, to cast off the manacles of dogma and tradition. The burden of this book is to redraw the scientific route radically, to redirect our intellectual, technologic, physical, and emotional faculties away from fundamentally flawed models of adding a few months to survival; instead, to conceive and strive for the substance of things hoped for, a real cure through early detection and prevention. To go from last to first.
There is one and only one goal for all of us—to ensure that all our intellectual efforts are directed toward the relief of humanity’s suffering. Suffering is what I see on a daily basis and what I chronicle in The First Cell. And where human suffering is concerned, scientific and emotional, medical and poetic impulses merge effortlessly and become inseparable. This synthesis, representing a rival paradigm of cancer research and treatment, even of writing about it, this dialogue of compassion, this science of empathy, of care and concern, can liberate us from the confident complacency of assumed righteousness in the way things are done, liberate us from the mental cages we have inadvertently imprisoned ourselves in. Our lives are at stake. Our future is at stake. Let new technology and new ideas rearrange our laboratories and our psyches, break the stalemate. Let us assume responsibility and seize the opportunities. Let us deconstruct what has become an indifferent science and reconstruct it through the prism of human anguish.
Kaun seh pai ga laikin meri aankhoun ke azab
Kis ko yay hausla hoga kay hamaisha dekhay
Apni palkoun ki saleeboun se utartay huay khwab
Jin ki kirchioun ki chubhbhan roh mein buss jaati hay
Zindagi, Zindagi bhar key liyay kur lati hay
—AHMAD FARAZ, “EYE BANK”
Who will be able to bear though
the ruin my eyes have seen
Who will be so brave
keep their eyes always open
Even as chimeras roll down
the branches of their lashes
Even as shrapnel twists
and encamps in the breath
Even as life cries out
for the rest of life
—TRANSLATED FROM URDU BY ANJULI FATIMA RAZA KOLB
ONE
OMAR
The Nobleness of Life Is to Do Thus
There’s a special providence in the fall of a sparrow. If it be now, ’tis not to come; if it be not to come, it will be now; if it be not now, yet it will come: the readiness is all.
—SHAKESPEARE, HAMLET, ACT 5, SCENE 2
I ONLY SAW OMAR TWO OR THREE TIMES WITHOUT NAHEED, HIS mother, in the roughly sixteen months of our acquaintance in New York. It is hard for me to think of them separately. From the first message I received from Omar in the summer of 2007 to my last glimpse of him as he lay dying with his mother curled up next to him in bed, I was exquisitely aware of the unique privilege it was to be witnessing this sublime relationship. Of course, love is never quantifiable. The friendship alone that existed between Omar and Naheed would require new heavens and new earths to accommodate it.
arz o sama kahan tiri vus.at ko pa sakey
mera hi dil hai vo ki jahan tu sama sakey
—KHWAJA MIR DARD
The sky and all the planets could not comprehend your expanse
Only my heart has the largeness to embrace the anguish
Naheed brought her two sons to meet me in September of 2007, shortly after I had moved to New York. Omar, the thirty-eight-year-old elder son, a graduate of Oxford and Columbia, had been diagnosed with a highly malignant osteogenic sarcoma of the left shoulder.
They had come for dinner. Omar had received a round of aggressive chemotherapy a few days before, and his mouth was a battlefield of raw ulcers, abraded mucosa, bleeding gums. As we sat down to an elaborate meal with family and a few close friends, Omar calmly produced a bottle containing some sort of a bland, soothing drink and sipped away as if it were an exclusively prepared gourmet meal, all the while entertaining us with his signature brilliant quips and observations. Such was his class, such his chic.
I can divide my association with Omar into three distinct phases. The first phase starting long-distance in the early summer of 2007 was all business: we were preoccupied with questions of what hospital he should choose, which surgeon; whether he should seek a second opinion in Boston; whether he should receive one combination of chemotherapy or another.
The second phase came when he started the dreaded but inev
itable slash-poison-burn cycles. Omar underwent radical surgery first, where surgeons tried to remove the tumor in its entirety. Reports from the excised mass unfortunately showed that cancer had already spilled into the veins. This was essentially a death sentence. In an attempt to eradicate the microscopic tumor cells, aggressive rounds of chemotherapies and radiation therapies were initiated. He settled more or less into a routine of sorts, punctuated by periods of pancytopenia, or a decrease in the number of blood cells; an intense susceptibility to infections; excoriated mouth; an occasional hospitalization due to sepsis; and finally, a brief period of respite, only to be followed by more of the same.
He suffered horrible toxicities from each treatment and derived little benefit. The tumor continued to grow. One week, a nodule sprouted in the lung, where it appeared surreptitiously on the CT scan. Another morning, a tender, red lump appeared on the wrist.
Once during this time, I asked Naheed in front of Omar why she did not go back to Karachi for a few days. Her mother was ailing, and Naheed needed to fetch her own things, as she was now planning to stay for the long haul, at least until Omar’s chemotherapy ended. “He will not let me go,” she simply said. I looked at Omar. It was true. He could not bear to let her out of his sight. “Azra apa, [apa and aps are terms of respect accorded an older woman],” he said, “if a mother is around, nothing bad can happen to her child.” So Naheed, who had come for a few days to New York, ended up staying for eighteen months, spending practically 90 percent of her waking time either with Omar or working on something related to him.
Surprisingly, this second phase, perhaps the most exhausting for any normal individual, proved to be the most productive for Omar. He was teaching at John Jay College; he was analyzing current events; he was teeming with original ideas; he was writing profusely. Above all, he was confident and optimistic. He was newly married.
He never lost the life of the mind. He came to dinner at my place in May 2008, when Richard Dawkins was visiting. Naheed had brought her fabulous book, Kashmiri Shawl, as a present for Richard, who was thrilled to take it home to his wife, a fellow aficionado. Omar had prepared a series of questions to ask and had a long chat with Richard. In early June, Omar called me one evening to say that, as opposed to someone who has come up with a list of the hundred books one must read before dying, he had compiled a list of a hundred books that one must read in order to live. Would I be interested in going over the list with him? My friend Sara Suleri Goodyear, professor in the English department at Yale, was staying with me at the time. We were both delighted at this idea and arranged for Omar to come over for dinner with his list. That evening turned out to be exceptionally stimulating. Sara and I offered our remarks on the titles that Omar rolled out with a twinkle in his eyes. Most of our own personal favorites appeared on his list—from Homer, Plato, Aristotle, Herodotus, Thucydides, and Virgil to the Old and New Testaments, the Bhagavad Gita, and the Quran to Machiavelli, Omar Khayyam, and Aesop’s Fables. He listed Augustine, Cervantes, Dostoevsky, Tolstoy, Ibsen, Flaubert, Proust, Lampedusa, Ishiguro, Rushdie, Adam Smith, Darwin, Hawking, Stilgitz, Pinker, and Bertrand Russell to Feynman, Kuhn, and Diamond. The entire list can be seen in the article I wrote about him for 3 Quarks Daily. After he left, Sara and I talked late into the night about Omar. We marveled that someone so captivated by life, so engaged, so erudite, so young, could demonstrate such equanimity in the face of almost certain death.
The third phase of my acquaintance with Omar began around September 2008. He was now on a slippery slope and knew it. Despite multiple surgeries to remove metastatic lesions, including parts of both lungs, he continued to experience recurrences at distant sites. On the day we came together to celebrate his fortieth birthday, he was diagnosed with a large mass on the arm even while receiving chemotherapy. This was not good news.
Omar’s family responded. Naheed, his best friend, Noor, and his devoted, inspiring, and lovely wife, Mursi, brought him to see Dr. Gerald Rosen, a well-known bone and soft-tissue sarcoma expert at St. Vincent’s Comprehensive Cancer Center. Gerry advised a second round of radical surgery to remove practically half his shoulder, arm, and chest, hoping that would excise a wide margin around the primary tumor, which Gerry felt strongly was the principle origin of the malignant cells. Gerry offered to arrange with surgeons he knew to undertake the risky and extensive surgery, insisting that this was absolutely essential. With Omar’s tumor, as with most solid tumors, Gerry felt that if it couldn’t be cut out, the battle was already lost. The surgical team at the treating hospital was not in favor of this, and Omar was torn. The four came to my office after their visit with Gerry. Omar pointedly asked my opinion, and I was blunt with him. “The radical surgery Gerry is recommending is an enormous risk, but it is the only lifesaving measure. You are young, and the odds are high that you will get through it fine. Give yourself a chance and go for the surgery.” The alternative was an experimental trial. Under the best of circumstances, as I told Omar, trial drugs would prolong his life by a few months. Surgery represented the only possibility of a cure, even if it was fraught with potential catastrophes. But if he wanted to pursue an experimental trial, I told him, I promised to get him any drug he wanted. Omar listened calmly and finally said he would think about what I had said.
Informing Omar’s thinking were his two siblings, who had been working valiantly throughout to save their brother’s life. They searched incessantly for news of any novel approaches to therapy or announcements of clinical trials. Sara, Omar’s sister, came to see him with her adorable little boy, and Omar was immensely cheered up by their visit. (One of the loveliest things about Omar was that while he was interested in big things, he knew how to be genuinely happy in small ways.) He brought Sara over for dinner one evening. I was astounded by the detailed questions Sara asked me about Omar’s situation, the choices available to him, his immediate and long-term prognosis. His brother, Farid, was completing his doctoral dissertation at Brown, but he nonetheless spent every moment he could spare with Omar. Farid accompanied Omar to his medical appointments whenever he was in town and stayed with him at the hospital when Omar was an inpatient. One evening as they were leaving my home, I was greatly touched to see Farid quietly adjust the sling on Omar’s arm and help him into his coat without a word from Omar, who continued talking to me the entire time.
Although deeply involved, Omar’s family as well as his friends completely respected Omar’s independence and supported him unconditionally whether they agreed with his decisions or not. They stood resolutely by him and faced the tragic choices with a fortitude that reminded me on more than one occasion of the famous line from Faiz Sahib: “Jo aye aye ke hum dil kushada rakhtay hain” (Let whatever is in store come; our hearts are capacious).
In the end, Omar decided against the radical surgery that Dr. Rosen had recommended. He called me a couple of days later to ask my help in getting him enrolled in an experimental trial. He subsequently began one at Montefiore Medical Center and seemed in an unusually good mood when he and Mursi came for lunch at my place in November. By early January, however, the trial had failed, and he was exploring other possibilities with his usual vigor and velocity. We were all frantically searching. He became fixated on a drug called dasatinib, which was being tried in his type of sarcoma, although he was reluctant to participate in another experimental trial because it would restrict his ability to try other therapies. I promised to obtain a compassionate exemption for him from the makers of the drug and wrote a single subject protocol requesting the drug for him.
Omar had now lived through seven major surgeries—removal of practically half the shoulder followed by removal of parts of the right lung and then the left. He had received round after round of toxic chemotherapies with bouts of radiation treatments in between. He then enrolled in experimental trials with zero benefit. Meanwhile, the tumors kept popping up in new parts of his body.
OMAR’S PREDICAMENT HIGHLIGHTS how spectacularly we are failing to treat cancer.
His treating oncologists and I knew that the chemotherapy or experimental drugs he received following the failure of the original surgery had zero chance of curing him. If palliation was all we could offer postoperatively, what was a better option—to treat or not to treat? Was it cruel to Omar and his family to keep suggesting new drugs, which would give him a few additional weeks at best, when the writing was on the wall? It’s not clear they ever registered how short term any benefits would be. Omar and his family fully believed that, if a drug were FDA approved or at least in FDA-approved trials, there would be lifesaving benefits to offset the pain of any side effects. Did they really comprehend the fact that any survival benefit would be measurable in weeks?
The expectations of patients are compounded by the action of regulators. It takes ten to twelve years to bring a new cancer drug into the market at a prohibitive cost of anywhere from $500 million to $2.6 billion. Extensive intellectual and financial resources as well as time are invested in conducting preclinical research to identify potential new therapies for cancer, but these rarely translate into any real benefit for the patients. Only 3–5 percent of cancer patients participate in experimental trials; of these, only 3.8 percent of the participants in phase 1 trials between 1991 and 2002 achieved an objective clinical response. The results for phase 2 and 3 trials are not much better.
Recognizing the unmet need in oncology and pressured by advocacy groups and cancer patients, the FDA is willing to approve an agent if it can prolong survival by a mere 2.5 months over existing treatments. Even with this low bar for approval, only 5 percent of drugs make it to market. Cancer has the lowest success rate among twenty-one disease indications. Those few drugs that are approved might as well have failed; once they are administered in non-trial settings, the results are no better than those that were not approved. This is partly because of how trials are conducted. Subjects participating in experimental protocols are handpicked and generally in reasonable physical shape. They have to pass strict eligibility criteria, including a good performance status, normally functioning heart, lungs, liver, and kidneys, and be free of any serious comorbid condition. Most cancer patients are more decrepit, suffering from additional comorbidities. Whatever little advantage is achieved in prolonging survival under the rigorously supervised clinical trial settings is lost once the drug is approved and used freely by practicing oncologists to treat unselected patients.
