CR 163: Infusion 20, Thanks giving

Another two weeks, another infusion. Since my appointment with Dr. Hahn was at 9 am, I left my home at 7 am, not knowing what rush-hour traffic would be like on the dreaded Washington Beltway. Today it was fine - no delays - so I arrived at 8:15 am. To my surprise, I was immediately called in for vitals, then my checkup with Dr. Hahn. I noted that I still had occasional itching around my neck and scalp, but not as much on my legs. My rash seems to wander around from week to week. I said how I had noticed that a seborrheic keratoses on my cheek (covered by my beard) recently seemed to have grown in size. Dr. Hahn doubted that that was related to the nivolumab, but offered a referral to dermatology to check it out. Everything else was routine - my labs were fine, as usual, and we're staying the course with treatments for the foreseeable future.

I was done by 8:30 am. Since my infusion was not scheduled until 10:30 am, I went to the Hopkins cafeteria and got an omelet made to order. The chef must have thought I looked wan, because I got a 3 pound monstrosity. I managed to do my duty, and needed no lunch. My infusion once again went much faster now that I do not need to provide vitals at the start, midpoint, and end.

During my infusion, I continued to devour N. K. Jemisin's new novel, The Fifth Season. I picked it up on Monday and finished it this afternoon. It's a remarkably original work that has earned a place on a number of best book lists of 2015. I'm now forced to wait for the next two books of the trilogy. Before that, I read The Wright Brothers by David McCullough, which was outstanding. Disappointing reads of late include Grisham's Rogue Lawyer (another lazy tell don't show polemic) and Ernest Cline's Armada (as unoriginal and boring as his Ready Player One was innovative and satisfying). I'm now reading The Only Ones by Carola Dibbell. Other books on my nightstand include Aurora by Kim Stanley Robinson and Geraldine Brooks' March.

On Thanksgiving day, my sons and I played in our church congregation's annual Turkey Bowl: two simultaneous games of touch football, one for young kids under age 12 or so, and the other for the older teens and adults. I think I was the oldest player on the field, and certainly was the one who ran the least. I mostly stood on the line of scrimmage, tried to block the occasional blitzer, and watch my boys and many friends have a good time. I thought of how at the Turkey Bowl four years earlier, I had just learned that I had bladder cancer. At the end of that game I walked with one of my good friends who was then serving as the leader of our lay ministry and told him about my diagnosis. His stunned reaction gave me the first insight that my journey might affect a circle much larger than my family. Over the past four years, I have gained a far deeper understanding of joy and sorrow than I previously could imagine.

The Sunday prior to this Thanksgiving, I was asked to give the opening prayer in our congregation's principal meeting. I concentrated on giving thanks for all the good in our lives. No requests, no favors, just gratitude. I spoke from the heart and recall very little of what I said. A number of people commented to me that they appreciated my focus on thanks giving. One member of the congregation later emailed:

I didn't want this day to pass by without thanking you for being you. Your prayer today in Sacrament Meeting touched  my heart deeply, and opened my soul to receive the words that were spoken in such a manner that I consider today to be a watershed moment in my life, and a day that I will reflect upon for the rest of my life. You and your family have been such a great influence in my life, and have given me joy, inspiration,  a lot of love, and a lot of laughter. Thank you, dear friend, for giving me insight and great hope. Have a wonderful Thanksgiving.

 I have found that a life filled with gratitude is a life filled with joy. And a life of joy is a life that brings us nearer to God.

CR Day 149: 19th Opdivo infusion

Today was one of my quickest infusion days at Hopkins: 3.5 hours from entry to exit. My labs were ready since I had my blood drawn on Tuesday (I spent most of yesterday at the FDA). Today I chatted with Dr. Hahn and two of his fellows - one from Brazil and the other from Portugal. I mentioned that I had attended the SITC conference on November 7, and learned just how quickly changing was the field of immunotherapy cancer research. Dr. Hahn had a conflict and was unable to attend the conference, but agreed that the field was white hot.

As part of his usual checkup, I said that I recently had noticed a light rash on my lower legs, especially around my calves. My legs badly itched as soon as I put them in a bathtub of hot water, or the hot tub, but otherwise were fine. He examined the rash carefully, and asked if I had a rash anywhere else. I replied that it did not think so, although at times I would catch myself scratching around my neck. He did not see any visible rash around my neck, and said that it could be nothing, or it could be an indicator that my body was beginning to react to the nivolumab. He urged me to let him know if the rash got any worse, or if my body showed any other unusual symptoms. Barring any toxicity issues, he said that he agreed that I should keep going with the treatments. I was already scheduled through December, so we scheduled infusions through the end of February.

I waited in the infusion waiting room for about an hour for a chair to open up, but once I was seated the drug was ready and waiting - a first! Better yet, the infusion nurse said that I was no longer required to have my vitals taken three times during the infusion.  My port was quickly accessed and  and in 70 minutes I was done.

Each day Jennifer and I give thanks that my cancer has retreated and that my life has been extended. Each day is a gift from God, and I try to live my life with an attitude of gratitude.

CR Day 148: FDA hearing; summary of my case

Today I gave testimony at a committee hearing at the Food and Drug Administration. The forum was the FDA's joint Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) and Oncologic Drugs Advisory Committee (ODAC) meeting. They were considering an application to approve a new drug named MCNA for non muscle invasive bladder cancer. Although I have not been treated with that particular drug, I was asked by BCAN's executive director, Monica Smith, to provide a brief statement of my journey with bladder cancer to illustrate the need for new drugs, and to remind the committee of the importance of their work. My statement followed Monica's statement, who spoke of the extent of bladder cancer and the fact that the FDA has not approved a significant new bladder cancer drug for nearly 30 years. 

For what it's worth, following is the outline that I prepared for my statement:

Name
Although I'm a patent attorney, I'm here as a BC patient. No financial relationship or compensation by any person or entity. 
Blogging re journey: search for Ken's Cancer Blog. About 350 entries, hundreds of thousand of views. No ads or compensation. BCAN volunteer. 

Diagnosed in Nov 2011 at age 49
Uro: BCG candidate if NMIBC
1st TURBT inconclusive for staging
Intense review of literature and consultations to know options
Second TURBT: MIBC, primary tumor T2b, plus 10 other tumors T1 and CIS. High grade micropappillary
Baseline CT and PET negative for mets
Concluded bladder could not be saved
Consensus: neoadjuvant GemCis chemo
CT after 3 rounds showed mets in multiple nodes

Discontinued chemo, rushed into surgery (RC with neo, prostectomy, 61 nodes)
Surgical pathology trifecta: upgrade to T3, andenocarcinoma in prostate, and 12 positive nodes
NCI SEER data show that 85% of mets BC die within 5 years.  
No established second line therapy
Enrolled in clinical trial sponsored by Dendreon but randomized into control group: watchful waiting. Ongoing neobladder issues (strictures, nocturnal incontinence, sleep deprivation). 

15 months later, distant mets found in supraclavicular node, confirmed by biopsy
Debate among treatment team re next therapy: 3 supported more chemo, 2 opposed
Commenced ddMVAC in Sept 2013. Discontinued after 3 rounds. Peripheral neuropathy. Mets stable for 9 more months. 
Distant mets resumed growth in fall 2014. While being evaluated for a clinical trial at NIH, CT scan found extensive PE. Treated with LMWH. 
By Jan of 2015, tumors were extensive, growing at >1 cm/month

Evaluated multiple immunotherapy trials, first mets BC patient in nivolumab trial at JHUH
Nivolumab (Opdivo) is an anti-PD1 drug being developed by BMS
After 6 rounds, CR, target tumors NED. 
As of 11/5, Largest non-target tumor is 7 mm on long axis. 
20th infusion tomorrow.  Protocol calls for up to 2 years of drug. 
Durability unknown.

I get lots of Q's through my blog and BCANs web site: crying need for new therapies
Not a doc. No medical advice. Encourage patients to be proactive, seek 2d opinions, look at clinical trials. 
Grateful to my health care team, researchers, pharma, NIH, and members of this committee. 
No position on MCNA. Many patients and their families rely and depend upon your work to evaluate and decide whether to approve new therapies. The need is great. 

Thank you. 

CR Day 139: Two videos explaining immunotherapy

From time to time I've been asked to explain how Opdivo (nivolumab) works. I usually mumble something about how the drug uses the body's immune system to attack cancers cells by using an anti-PD-L1 mechanism to defeat the cancer cell's defenses. Most people politely nod and have no idea what I'm talking about. Neither do I. But here are a couple of short videos that explain what's going on in lay terms. First, a whiteboard sketch from Dana Farber Cancer Institute. Second, a film from Cambridge University showing killer T cells attacking cancer. There are about 5 million T cells in each teaspoon of blood, and Opdivo gives them the ability to detect and kill cancer cells that previously were ignored because they didn't look like cancer cells. It's amazing to think about everything that is going on inside the human body. I'm glad that my clinical trial has been working n my cancer.

On Saturday, I attended a forum regarding recent advances in immunotherapy, and heard from doctors regarding the latest advancements in fighting cancer. I hope to post a more detailed summary, but their enthusiasm of how we are entering a new stage in defeating cancer was infectious. I am more hopeful now of my long-term prognosis than I ever have been since I was diagnosed with metastatic cancer. I am grateful to the ongoing research efforts and am glad that, by participating in a clinical trial, I might be helping others in the future.

CR Day 135: 18th infusion, clear CT

Today was another long day at Hopkins. Two hours each way in rush hour traffic. My port was easily accessed and gave a strong return of blood for my lab work -- whatever problems I had earlier in the year with a sheath growing over the tip have been resolved. I went upstairs for the CT scan and was told that someone had forgotten to obtain insurance company preapproval for today's scan. I could either wait for hours while Hopkins tried to get the approval; skip the scan; or sign a waiver that I would pay in case Hopkins could not get approval. I chose door 3, signed the form, and had the scan.

Insurance company approval is needed because, although I am in a clinical trial sponsored by Bristol-Myers Squibb, Hopkins still seeks insurance company payment for costs that are customary for ongoing monitoring of a metastatic patient. That apparently includes CT scans every 6 weeks, and the accompanying lab work and doctor's visits. Bristol-Myers apparently pays for the nivolumab drug and the associated costs to infuse it, as well as various supporting costs such as a portion of the salaries of the clinical trial nurse and other health care professionals. Running those trials is not cheap, and I am glad that I'm not having to pay for the drug. According to a recent Wall Street Journal article, the retail cost of Opdivo to treat metastatic melanoma is over $12,000 per month.

After the scan, I had to wait a couple of hours for the results to be read and my drug to be released from the pharmacy. I read the newspaper in the Hopkins cafeteria while I drank a couple of liters of Diet Coke to flush the radioactive contrast out of my kidneys. Eventually, I met with Dr. Park, one of Dr. Hahn's fellows, and put him through the paces while getting his views on the durability of nivolumab. He was not as up to date on the literature as I was, and took some time to do some searches and skim the latest articles before telling me that there was no data on point, and the best he could do was extrapolate from the same articles that I discussed in my post of two weeks ago. We also discussed how long I should continue with the trial, saying that I was of the view that I should ride this horse as long as it would carry me. He was inclined to agree, but said that we should discuss it with Dr. Hahn, who fortuitously entered soon thereafter. Dr. Hahn saw no reason to stop treatment, and said that, as long as there was no progression of disease, the only thing that I should keep in mind was the chance of toxicity, although the risks of that are relatively low, and this review suggests. 

I noted how I had noticed an increase in leaking from my neobladder at night, or any time I was in a horozontal position, for that matter. We discussed whether I should increase my dosage of imipramine, or try something else. Dr. Hahn said he wanted to discuss that with some of his colleagues, and I said that I would make a more conscious effort to track the frequency and circumstances of when my neobladder leaked.

Dr. Hahn said that the results of my CT scan of my neck, chest, abdomen and pelvis showed no change from my last scan in August: no evidence of disease, no inflamed nodes, no suspicious tumors. The pulmonary inflammation from my post-Africa infection had dissipated, and everything looked clear. Yay! I went up to the infusion center and had 377 ml of Opdivo pumped into my body, along with a liter of saline. When I reclined back, I started to leak. I smiled as I hurried to the bathroom, pulling along my infusion machine: I'd much rather deal with peeing my pants than dying of cancer.

CR Day 121: Infusion 17; research on nivolumab durability

Last night I stayed up until 1 am so I could finish reading Neal Stephenson's Seveneves, a cracking good yarn about efforts to preserve humanity following the destruction of Earth. Less than 5 hours later I got up after having wet my bed due to my malfunctioning neobladder. The 50 mg of imipramine that I take each night has helped to decrease the frequency of spontaneous nocturnal voiding, but it still happens enough for me to celebrate each night that I get an uninterrupted sleep. I keep a large waterproof mattress pad underneath my sheet to protect the mattress from stains and smells. After being jolted awake this morning, I quietly left the bedroom so as to not disturb Jennifer. I sat in the hot tub for an hour and saw several shooting stars, reminding me of the meteoric "hard rain" in Stephenson's book. I got out of the hot tub as dawn was breaking and left the top down to cool off as I started my drive to Baltimore.

While waiting for my appointment with Dr. Hahn, I researched the latest data regarding durability of nivolumab. Bristol-Myers has not yet published any data from my trial, or any other Opdivo trial specific to metastatic bladder cancer or other types of metastatic urothelial carcinoma (searches can be run here). Recently published results regarding nivolumab on other types of cancer have been equivocal. For example, an October 20, 2015 Up To Date review of recent advancements in oncology reported the nivolumab had shown promising results in metastatic melanoma and hepatocellular cancer. A September  25, 2015 item in the ASCO Post found that around 20% of heavily pretreated patients with non-small cell lung cancer (NSCLC) had an overall response to nivolumab, and the median duration of response to be about 17 months. Another September 2015 report of a different NSCLC study of nivolumab and ipilumab showed overall responses of between 13 and 39%, with zero complete responses and median progression-free survival of 5-10 months - results the authors called "deep: and "durable." An August 6, 2015 article in Oncology Targets Therapies reviewed the literature regarding nivolumab and metastatic melanoma and concluded that nivolumab was better than conventional chemotherapy, with longer overall response rates and longer durability. At BCAN's August 2015 Annual Think Tank on Bladder Cancer, Dr. Efstathiou summarized the current status of immunotherapy and bladder cancer, including recent nivolumab data.

Armed with this unsatisfactory data set, I asked Dr. Hahn for his views on the likely durability of my complete response to nivolumab. He readily conceded that there was no data directly on point. All we could do for now is to look to how nivolumab was working on other cancers (which is what I had been researching), as well as looking at data from other PD-1 drugs on mets bladder cancer (such as MPDL3280A). But none of that data sheds much light on how long I might have before my metastatic cancer returned. Dr. Hahn said that researchers generally assume that no drug that they are researching will "cure" cancer; instead, in multiple mutation cancers like mine, once the PD-1 avenue was blocked, the cancer likely would start growing using another mutation. But he hastened to add that there was no way to know if, or when, that might happen to me. He sympathized how I was adrift in a sea of uncertainty regarding the durability of my CR, and said that my experience would help inform others who come later. Time will tell.

We then reviewed some amendments to the clinical trial protocol. The most relevant one to me was a new option of voluntarily discontinuing treatment following a complete response, with the right to resume treatment if the cancer returned. If I was to discontinue my every-other-week pattern of infusions, I still would be closely monitored through checkups and CT scans every 6-8 weeks to see whether I had any latent side effects or whether the cancer was growing again. I was given a copy of the new protocol, and we agreed to talk about that option in on November 5 when I will have my next CT scan and infusion. I continued to mull over the yet-unanswered question of nivolumab durability while I received my infusion.

My literature review and questions to Dr. Hahn were prompted by discussions Jennifer and I have been having about the future. I'm slowly starting to lift my eyes to the possibility that I might live longer than the statistics suggested when I was first diagnosed with mets BC (e.g., 90-95% chance of dying by May 2017). But without any data on how others have fared using this therapy, I have no basis to form expectations for how long I may live. I certainly can't assume that I will fit into the conventional mortality tables for a 53 year old white male. According to the Wharton School's longevity calculator, which does not factor in cancer, I'm likely to live well into my 80's, and have only a 5% chance of dying before I'm 60. In fact, those statistics have been inverted for me for the past three and half years: a 5-10% chance that I'd see age 55, let alone age 60. It's now looking more likely that I'll make it to 55. Beyond then: who knows?

Not having an objective basis for my life expectancy continues to leave me wondering how I should make all sorts of decisions. Do I invest for short term protection or long term gains? Do I consider going back to work? Do we sell our lake house after it is rebuilt from the flood caused by a broken pipe? Next year, our nest may be empty. Do we downsize? Do Jennifer and I explore the idea of full-time missionary service for our church? Jennifer and I have kicked around these questions, and have not found an acceptable way to work towards the answers. One approach is, since we don't know what weight to give it, we pretend cancer is not a factor and talk about what we would do. That's led to some interesting discussions, but no resolutions. Time will tell.

median progression-free survival time of 4.9 to 10.6 month - See more at: http://www.cancernetwork.com/wclc-2015/first-line-nivolumab-ipilimumab-demonstrate-deep-durable-activity#sthash.sPfV7yHI.dpuf

median progression-free survival time of 4.9 to 10.6 month - See more at: http://www.cancernetwork.com/wclc-2015/first-line-nivolumab-ipilimumab-demonstrate-deep-durable-activity#sthash.sPfV7yHI.dpudepending upon the demonstrated deep and durable activity

CR Day 107: 16th Opdivo infusion; goodbye Xarelto

As usual, the day before my scheduled infusion, I went to the local Labcorp office for a blood draw. Theoretically, having the draw the day before should ensure that my lab work is in place so the Hopkins pharmacy can custom-make my dosage of nivolumab, which otherwise takes at least three hours to compound. Yesterday, however, the Labcorp tech failed to draw enough blood to do the CBC work. This meant that Hopkins had to do my blood work and I got to wait.

Dr. Hahn and I discussed whether I could discontinue Xarelto. It's been exactly a year since my pulmonary embolisms were serendipitously discovered at NIH when I was being evaluated for a clinical trial. There has been no evidence of further PE's in my last eight CT scans. My body is not currently burdened by any metastatic cancer, thereby decreasing the risk for PE recurrence. Dr. Hahn was comfortable with my stopping Xarelto, saying that the risks of DVT or PE were much lower. Plus, I'll be having regular CT scans for at least the next two years through the clinical trial, so the risk of having an undetected recurrence is virtually nil.

Three hours later, my drug was released and I had my sixteenth infusion. I get my infusions sitting next to patients getting chemotherapy, and as I looked at the bald heads and gaunt frames, it seemed like a lifetime ago that I was one of those patients. In fact, it was only two years ago that I was suffering through ddMVAC. I hope that immunotherapy will replace chemotherapy, that the success rate will rise, the side effects will diminish, and more lives will be spared.

At least once a week, I review recent questions regarding bladder cancer at www.inspire.com and post responses. I focus on metastatic disease, where I have the most personal knowledge. I also have engaged in a number of one-on-one discussions with patients or their caregivers, and will on occasion point people to my prior blog entries where I have addressed the topic of their question. I also have been told by a number of patients that they have investigated and enrolled in immunotherapy clinical trials after reading of my good fortune. I'm grateful that others have been helped through my chronicles. When I started this blog, I had no idea what it would turn into. And I have no idea how long it will go.

Thirty six years ago, Dan Fogelberg released an album entitled Phoenix. The last song on the flip side of the record was titled, Along The Road. Recently I've thought about those lyrics in light of my journey with bladder cancer:

Joy at the start, fear in the journey
Joy in the coming home
A part of the heart gets lost in the learning
Somewhere along the road

Along the road your path may wander
A pilgrim's faith may fail
Absence makes the heart grow stronger
Darkness obscures the trail

Cursing the quest, courting disaster
Measureless nights forebode
Moments of rest, glimpses of laughter
Are treasured along the road

Along the road your steps may stumble
Your thoughts may start to stray
But through it all a heart held humble
Levels and lights your way

Dan Fogelberg died of metastatic prostate cancer in 2007, at age 56.

As for me, I can't say that my journey with bladder cancer started with joy, and certainly there has been fear along the way. But I have found many unexpected joys, and look forward to many more moments of rest and glimpses of laughter somewhere along the road.