14
November 18
Sts. Peter & Paul, Richmond
Following the Gospel from Luke 18:35-43 about a blind beggar healed by Jesus, Deacon John offered a pertinent message on the hectic speed of life and suffering, quoting Pope Francis who spoke at Lourdes reminding those who suffer to always bear in mind that God hears their prayers and loves them: “You who are little, who are poor, fragile, you are the Church’s treasure.” Deacon John expressed that offering our suffering to the Lord is not pointless and can be redemptive. In that time and place the concept of the redemptive power of healing spoke directly to me, giving words as balm for my soul.
The Redemptive Nature of Healing
Everytime I attended Mass at Sts. Peter and Paul, I found myself looking up, craning to see the finer details of the 14 Holy Helpers. I had done my own research on the ceiling saints when I taught religion and had created an art study lesson with the paintings. The whole collection of these 14 saints were grouped together as The 14 Holy Helpers as an appeal during the Black Plague in Germany. With an overarching goal to make religion class fun and interesting so the students would want to come back, I created an art study lesson with the painting of the saints. Spread out throughout the church, the students craned their necks studying their saint and writing down any details they saw. We met back in the classroom and they would describe their saint. I had backup details about the saint’s life that would always add spice, usually about how they died or were martyred. At the end of the lesson, I paired them up to draw the church from a bird’s eye perspective with directions to raise their hands when finished and not to say anything. Then I would hover around until the first kids noticed and without fail blurted out that it was in the shape of a cross. The kids were very receptive to the lesson and I was proud when I would catch them at Mass staring at the ceiling saints. Now, alone in my pew I appealed to the 14 Holy Helpers, praying for their intercession with my own plague.
From little on I was always intrigued by the lives of Saints so when I saw a notice in August 2018 that the relics of Saint Padre were coming to St Cloud my interest was piqued. When I first saw the notice, I was disappointed because I would be back to school and not able to get to the weekday viewings, but a few weeks later, I was on medical leave with even more impetus to be among blessed relics. Admittedly, I knew very little about Padre Pio except being marked by stigmata and that he was my devout friend Greg’s favorite saint. In preparation to visit his relics, I read Padre Pio: The True Story, a heavily researched book that showed the great lengths the Catholic Church went to disprove or avoid sanctifying him. The Vatican sent a scientist who was an avowed atheist to review the stigmata and interview Pio. The scientist was so awed he converted to Catholicism. Pio himself was not a fan of attention and so his stigmata really tried his faith and personality. The biography made me realize that if he could embrace his suffering, I could make amends with my situation too. So I made a trip to St. Cloud to see some saintly scabs. Scabs. You know you’ve made it when people line up to see your scabs. Deacon John’s homily discussing the redemptive nature of suffering was personified in Padre Pio.
My first glimpse of the event at St. Mary’s Cathedral started with the lines of people formed outside the building. The rows of dearly devoted continued down the steps and through the cathedral to an area immediately in front of the altar. For nearly an hour, the young and old, fit and wheelchair-bound all waited quietly. The cathedral’s impressively ornate structure was made even more impressive with the collective faith.
As I made my way closer to the front, I caught glimpses of the shrine guarded physically by the tour’s security detail in black and symbolically by Knights of Columbus in full regalia. I was about halfway up when the Knights of Columbus executed a very elaborate change of guard. The ostentatious robes of the Knights were in contrast to the display of Pio’s plain clothing: a well-worn shirt and dark frock he wore along with a cloth yellowed over time were hung up. Dried blood/scabs from the stigmata were enshrined behind glass. The faithful would touch the items or touch a rosary to them. These items he touched personally were first order relics. Items that touch them can be considered second order relics. I made my way through the relics and left, not realizing I was crying. It was a powerful moment I’ll always treasure. Since that day, I noticed more the crosses others bear, some with humility and humor and others with woe and spite. I also knew that my cross is mine and I would not switch with anyone else.
Pio inspired me to pray for grace. Grace to accept what comes next while I prayed that my progression-free survival is long, that my medications are safe and effective. The redemptive nature of healing applied spiritually, of course, but also quite literally. My first line treatment was immunotherapy called Herceptin, a biotherapy engineered to specifically attack the protein on a cell that is overexpressed, Her2. Unlike chemotherapy which indiscriminately destroys all cells, Herceptin is target therapy, a snotty killer and only takes out Her2. In her article, “Analogies in Oncology: Explanations Made Easier,” oncology nurse practitioner Wendy Vogel offers the following analogy for how target therapy works:
The mechanism of action of some targeted therapies may also be explained by the analogy of a singles bar. The singles bar is represented by a cancer cell and receptors on the cancer cell. The receptor site is looking to “hook up” with its favorite dream lover (or ligand) for a romantic interlude. The romantic interlude is the process of hooking up: the receptor site and the ligand join (dimerization), causing downstream signaling to “turn on” (activation of) the pathways (such as the kinase pathway) so that the cell will replicate, metastasize, or lose normal apoptosis.
The targeted therapy can be visualized as “Mama,” who is going to stop the romantic interlude… If Mama stops the action at the singles bar door—working at the cell surface to keep the growth factor receptor and its ligand from joining (dimerization)—that is how drugs like EGFR and HER2 inhibitors work.
Often I mentioned my desire to have a long-term relationship with Herceptin because I knew if my Her2 cells would further mutate, it would no longer be effective. In medical parlance, I would fail Herceptin not the other way around. Yep, it seems like you are blaming the victim, but scientifically it meant my freakishly clever cells found a way to mutate again and no longer be the target for Herceptin. My zany brain wondered if the mutated cells could possibly give me a super power instead; I tried to time travel and shoot webs from my wrists, but no luck.
Unlike many oncology treatments, Herceptin is well tolerated because it is a targeted therapy. My side effects were a slightly runny nose and some creaky joints. Actually, my aches made me wonder if what I felt was side effects, cancer progression or merely common effects of aging. It was a constant struggle not to become a valetudinarian analyzing every nascent symptom. I could understand “worrying yourself sick.” Compared to the laundry list of side effects from chemo, I actually worried that because it was easy to tolerate, it was not effective. I had read somewhere the tamoxifen was known to be effective if the side effects were felt. I felt them–creaky joints and sore feet plus aggravated menopause effects.
After years of being puzzled by each drug having two names like my TCHP regimen for Taxotere (docetaxel), Herceptin (trastuzumab), Paraplatin (carboplatin), Perjeta (pertuzumab), an infusion nurse explained that the capitalized was the brand or trade name and the other medical or generic. Before I started on TCHP, I knew precious little about the drugs designed to attack the cancer and extend my life, but my friend Julia and infusion nurse Ann recommended a book by Robert Bazell: Her-2: The Making of Herceptin, A Revolutionary Treatment for Breast Cancer. The book is as the publisher described: “a riveting account of how Herceptin was born. Her-2 is a story of dramatic discoveries and strong personalities, showing the combination of scientific investigation, money, politics, ego, corporate decisions, patient activism, and luck involved in moving this groundbreaking drug from the lab to a patient’s bedside.” Like the title claims, Herceptin is revolutionary. Her-2 helped me understand how the targeted therapy worked. The book was compelling to me as I had a vested interest but setting aside my obvious bias, it truly was “a complex biological mystery; a drama of high finance; a series of non sentimental, intelligent love stories; and a terrific vindication of stubbornness in a good cause.” It’s a good read even if you don’t have cancer, but I am pretty much going to give you the book report on it for two reasons: it’s well written and highly educational.
At the time Herceptin was developed by Genentech, a biotechnology company in San Francisco, the pharmaceutical industry left pure research to university scientists, then the drug companies used their findings to create useful drugs. In 1979 a group of scientists from several universities discovered oncogenes, genes with potential to turn a cell into a tumor cell. Twenty-one years after the Her2 oncogene was first identified in 1982 as an oncogene in rat neuroblastomas, Genentech’s Herceptin received FDA approval. It was quite a pharmaceutical saga.
Genentech worked with UCLA oncologist Dennis Slamon who explained that with Her2 the gene is mutated and overexpresses the Her-2 protein, and when “the cell is overloaded with signals that cause it to grow out of control– to become cancerous. A typical breast cell carries about 50,000 Her-2 neu receptors on its surface. When the gene is mutated the number jumps to between 1 and 1.5 million.” After the gene was discovered, scientists believed that stopping the protein would control the cancer. Oncologists ordered biopsies to test for the receptors and determine how strongly Her2+ the tumor is. Genentech hired Peter Carter, a scientist, to take mouse protein and humanize the monoclonal antibodies. “A monoclonal antibody is a laboratory-manufactured solution containing millions of identical copies of a single antibody, all of which attack precisely the same target.” Genentech’s Immunology Division produced monoclonal antibodies and in 1990 tried human tests. Carter’s humanized antibody “succeeded brilliantly” and with unprecedented speed was ready in ten months. The timing for the drug was off, however, as shifts at top management at Genentech changed focus from scientific freedom for its scientists to corporate financial profits.
Though the drug held great promise, Genentech was not interested in investing in cancer treatment. It had tried and failed with previous drugs and was not willing to take on the risk. Although Slamon made many appeals,“Nobody gave a shit except him.” Herceptin was almost not a thing. Ironically, Breast cancer itself saved the day. When a top management’s mother developed metastatic breast cancer, the Her2 project went from nearly being shelved to full support. This gave me pause, but unfortunately the drug development business principles today have not changed and if developed now Her2’s potential would now not justify the cost. With a 25-30% minority of breast cancer patients testing her2 positive, it was not worth $150 million (in 1990) to bring it to market. Only with additional funding from Revlon, a donation from a wealthy patient and fundraising advocacy allowed Slamon’s UCLA lab to continue with human tests.
Prior to having a clear stake in pharmaceuticals with my cancer diagnoses, I had only a vague understanding of the drug trial process. In drug trials, if no problems are revealed with the small numbers enrolled in phase I, phase II proceeds, usually enrolling a few dozen patients. Phase III tests with hundreds or thousands to determine if it works well enough to apply for FDA approval. Before Her2’s trials could begin, oncologists had to be convinced to find patients to participate.
Her2 followed several patients’ experiences closely; Barbara was one of the fifteen in the three month phase I study. The Phase I patients were all considered terminal and became very close as they met frequently for treatment, which was great for support but horrible for morale as only one patient, Barbara, survived Phase I. If I ever felt sorry for myself, I would remember how incredibly aggressive Her2 cancer was and how fortunate I was to have drugs to treat it Despite having only one survivor, the study was deemed a success: “Standard measure of a positive response in a cancer trial is a reduction of the tumor mass by at least 50 percent. Slamon found 30 percent had positive responses, some dramatic.” My own experience was dramatic, I could feel my tumor shrink in only weeks after starting Herceptin. Prior to Herceptin it would have been treated with high-dose chemotherapy, which extended life in months but decimated the quality of it.
Forty-three women participated in Phase II with one total remission, one quarter with tumors that shrank and another quarter who remained stable. It hardly sounds like a success, but given the other treatment option was high dose chemo so brutal that doctors must “stand back and hope that the toxins knocked out the cancer so that it will not spread any more,” Herceptin was the bomb-diggity. Unlike the targeted therapy focused on specific cells, high dose chemo indiscriminately attacked all cells. To me, it was clear in the severity of side effects with the more cells affected, the greater the impact on the body. The success of Phase II brought a different way of viewing cancer: “Cancer cure had always been the great hope, but what if cancer control became an option?” I learned to accept my advanced cancer as a chronic disease, like diabetes or hypertension I had to accept treatable instead of curable. The ghastly thought of untreatable cancer made me accept my fate with a modicum of grace.
Meanwhile, patients who couldn’t get to the experimental treatments were starting to demand access to Genentech’s treatment. At that time most breast cancer organizations were based more on support than activism. Cue the lessons from the AIDS activists who forced “fundamental changes upon pharmaceutical companies, medical researchers and the FDA.” Compassionate access to not-yet-FDA-approved drugs to the critically ill was the rallying point, but Genentech was not interested as they believed compassionate access wasted resources, money and time. But in December 1994, demonstrators protested with a fifteen-car “funeral procession.” Genentech’s dilemma was that allowing exceptions outside the studies would produce results that would not help show if the drug worked or not and might delay awareness of the drug’s efficacy and even prevent it from receiving full approval. But the activists’ persistence and media attention finally pushed Genentech to offer compassionate access. Due to a limited supply, patients had to apply for a lottery and agree to be treated within protocols to produce data the company could use. Ultimately, the expanded access program actually helped Genentech win FDA approval.
More drama ensued. Phase III was expensive but for pharmaceutical giants, it was less challenging because they have hundreds of already profitable products in the market. But Genentech was a small company. If the drug failed, the company would also. Genentech’s small size also made it more challenging to recruit doctors, hospitals and patients to participate since the company did not have as much experience and clout as larger and older companies. Additionally, the academic physicians working in the trial had strong views and did not always agree which made it a tough sell when they would disagree in meetings with investors. Here I shudder thinking the drug that kept me alive might have been preempted by bickering.
Even the structure of the trial created divisions. One doctor described it as a team “sent on a mission to Antarctica without a coat.” Since there were a lot of breast cancer patients, most received care from local oncologists, not in major academic medical centers where the trials were held. The local oncologists were not willing to relinquish their patients to a trial with the narrow effectiveness as it only worked on HER2 positive cases. It was a double-blind trial so of those sent, half would get Cytoxan and Adriamycin and a placebo. When the double-blind arm of the trial was too slow to fill with volunteers, the option to get Cytoxan and Taxol with either placebo or the antibody was offered. This opened the trial to more patients as many had been excluded because they had already failed to respond to Adriamycin. Expanding the options helped fill the trial along with more aggressive recruitment lobbying to physicians and patients.
The effortss to fill the trial were aided when President Clinton announced new streamlined procedures for cancer drugs by the FDA following the recent death of his mother to breast cancer. Twice Herceptin was aided by a powerful man who lost his mother to breast cancer. If breast cancer was less prevalent, Herceptin might not have made it. This gave me pause when thinking of rare diseases and the limited drugs available in a horrid loop. Clearly prevalence encourages drug companies to find treatments that would be financially sustaining, but what about the rare cancer? The unfairness of the already unfair cancer is unfathomably frustrating. And again I feel the love/hate aspect of Big Pharma. Lives lost due to profit is unacceptable, yet the costs of one drug alone are mind-blowing: it takes“8-10 years and approximately $1 billion for a new drug to go from a chemistry model to FDA approval” in 2020. Only 14 percent of drugs make it to market. I owed my days to the pharmaceutical industry–big love–yet was appalled by the huge financial price–big hate.
The plot thickened with the promise shown by early results in “time to progression.” With standard treatment, recurrence averaged nine months after treatment began. Scarcely nine months after I had completed treatment, I had progressed to metastatic so that time interval always caught my eye. I had completed my year of Herceptin and Perjeta in October with clear scans. Since I had no active disease or symptoms, insurance would not cover surveillance scans. Those devious mutations seized the time to grow unchecked until the brain tumor near my vomit center grew large enough one day to make itself known. To be honest, I had planned to make complaints that would warrant a scan just for my peace of mind, but nine months did not seem long enough to worry me. There’s no benefit to playing a game of “what ifs.” Ultimately, it would not have changed the course of my medical history, but it was hard to know that there was no proactive way to screen for recurrence. And worse, the overall survival was unchanged even when metastatic cancer was caught earlier. The lack of control for this control-freak was an unmitigated horror.
Though the drug trial statisticians calculated that investigators would need to follow the participants for a year to find any meaningful benefit, early results showed that on average all the women in the trial, placebo or not, were getting new cancers far more rapidly than anticipated. “Another reminder of the insidious, highly malignant nature of Her-2/neu-positive breast cancers.” The same speed would be a benefit, yielding results sooner. Results Slamon termed “sensational.” Time of progression was lengthened and significant numbers of participants saw their tumors shrink or disappear.
In March 1998, the FDA granted Herceptin fast-track approval, within six months from submission. Approval was likely so manufacturing ramped up as individual doses were high, frequent, and might be prescribed for the rest of the participants’ lives. My treatment plan with Herceptin for years was “continue maintenance trastuzumab once every 3 weeks indefinitely.” (Before discounted by insurance contracts, each Herceptin treatment was over $10,000 eighteen times per year. Insurance is yet another love/hate relationship. I truly couldn’t live without it.) The trial showed the most benefit used with cisplatin than Adriamycin or Taxol especially in 65% increase in time to progression and half of the participants saw tumors shrink. Cardiac toxicity stuck nine percent more on Herceptin than the placebo, so protocols were developed to guard against the complication and treat it when it occurred. Often a break from Herceptin was sufficient. While I took Herceptin, I had echo-cardiograms to monitor my heart until I was on it long enough that we knew I would be able to tell if there was an issue. It was a relief to have one less scan, especially since I truly felt bad for my heart when I saw it beating on the monitor. It was perfectly healthy, but it had to work so hard, every beat was an orchestra of muscles and valves and whatever else I saw but did not recognize. I left those appointments in awe of my own heart.
For me the Her2 patients’ stories interwoven with the scientific and business side of Herceptin gave it a personal appeal and created captivating medical thriller. It would be easy to write this as a romance. The struggle to get together, timing all off, others trying to keep the couple apart, financial complications, personality conflicts, doubts, multiple breakups and then finally the happily ever after. Genentech saves lives and makes mad money. If it seems like a plot for a Lifetime made-for-tv movie, that happened too in Living Proof with Harry Connick, Jr. as Dr. Slamon. The book is far better than the 2008 movie, but Harry is McDreamy enough to watch for a couple of hours with actresses like Amanda Bynes, Bernadette Peters, Swoosie Kurtz, and Angie Harmon rounding out the cast.
In addition, I learned how drugs are named. For biological products, the drug name comes from a government agency assigning a name that includes a required prefix and suffix. Trastuzumab. Suffixes -zu for humanized and -mab for monoclonal antibodies. The trade name Herceptin came from Her as breast cancer is most often a woman’s disease and also part of the gene’s name. A marketing company whose core business is naming drugs recommended Tarcepton, as in intercepting the target. Genentech’s marketing combined the two into Herceptin. The name is also researched to make sure it is not copyrighted in any form and also not offensive in any language. I would have no place in naming drugs, but had often dreamt of a career naming fingernail polish, house paint or color crayons.
By now you noticed I’m a big fan of analogies. My favorite cancer analogy helped me visualize the therapy: “consider having the patient picture a golf ball, with all the little ridges around the surface of the golf ball representing receptors on a cell’s surface. If you were to roll the golf ball through a puddle of paint, some of those receptors would pick up the paint (the targeted treatment)” It was also easy for me to remember and appreciate due to my love of golf. The tumors are spiculated, with hideous spiny tentacles reaching out and invading other cells. I also suspected they are sticky and smell horrible.
A bitter pill of the success of Herceptin was as more patients taking it lived longer, many developed breast cancer brain mets, BCBM. Herceptin’s large molecules are too big to cross the blood brain barrier so the brain is left untreated, a sanctuary site. But in some bizarre justice, brain tumors and brain radiation are believed to perturb the barrier so some medicines can cross. In a self-limiting cycle, BCBM often excludes patients from participating in trials so less data is available which means fewer meds are an option. After Communion, I would pray that Jesus would cover and protect all my healthy cells and fire up my immune system with my meds to control any progression. In my mind–literally and figuratively–Jesus crosses the blood brain barrier for sure!
In the great medical bag of breast cancer treatment, targeted therapy drugs like Herceptin work on only one of the five subtypes of breast cancer: normal, luminal A, luminal B, HER2 and triple negative. The subtype flip from HER2- and hormone receptor positive to Her2+ and hormone negative made my stomach flip too. According to Dr. E, this discordance between primary and metastasis happened in about 25% cases and of those maybe 10% switched again. It made me concerned that those rat bastard cells continued to mutate, but I’d remind myself that with eight years between stage I and stage III, the progression was slow. Slow rat bastards. Meanwhile, I kept my eyes on any advances heralded in reputable oncology journals and would see headlines proclaim a new advance in breast cancer, but another subtype so would not benefit me or I would see interesting studies for HER2 positive but only produced thus far in the laboratory. With the slim odds of a drug making it to market, I kept my hope threshold low too. Genentech had created a whole cast of drugs in combination with all-star Herceptin: laptatinab, pertuzumab, trastuzumab emtansine that might be options after I failed Herceptin. Scott’s coworker and whip-smart friend, Todd, whose mighty brain held both our degrees in English and physical therapy, could turn a medical phrase like nobody’s business. He stressed that the longer I lived, the longer I would live as medical advances improved survival. It helped me think of each day as the next best, not as one of the last.
I had always been an avid reader, but reading about Herceptin was truly redemptive for me. It left a bookmark on my soul.