Phase One Clinical Trial: Cabozantinib

             On Thursday, October 23, David started a Phase One clinical trial of cabozantinib. He takes the pill at home each morning and goes to MGH twice a week to check his blood counts.

            For the first two weeks, ending two days ago, he was allowed to take hydroxyurea to lower the white blood count while we wait to see if the cabozantinib will attack the blasts.

Date	White Blood Cell Count	Percentage Blasts
6-Oct-14	2.2	2.60%
10-Oct-14	2.7	8%
15-Oct-14	3	9.20%
23-Oct-14	15.7	47%
24-Oct-14	14.9	53%
26-Oct-14	15.5	65%
30-Oct-14	8.81	55%
2-Nov-14	6.68	33%
5-Nov-14	4.8	39%

            The lower blast percentage is good news, however, it is too early to know whether the cabozantinib is having any effect.

            Last Sunday, Jim, David, and I drove to the Bronx to visit Peter, Xiomara, and Andrew. Monday evening we (sans Andrew) attended R’els first concert with the Oratorio Society of New York. They performed Haydn’s The Creation in Carnegie Hall. It was superb.

Very Sad News

Jim wrote the following email last evening. I couldn’t express it better:

David and Mary and I met with Dr. Amir Fathi of Mass General Hospital on Wednesday. David is feeling very well and strong. Unfortunately, that piece of good news is the only good news.

The leukemia cells are back, and likely to grow. There is no treatment known that has much chance of working. In fact, Dr. Fathi said that given David’s history of treatment and relapse, his chances of surviving this leukemia are infinitesimal. The leukemia could be fatal within a couple of months (very roughly speaking) with no further treatment. With treatment, it is possible the leukemia can be controlled for a while. It is also possible that that the side effects of treatment could be bad, or that the treatment could fail to slow the leukemia down at all.

Dr. Fathi reviewed three experimental possible treatments, all of which have some low chance of working for a while. David chose a Phase I clinical trial of cabozantinib. Dr. Fathi himself is conducting this trial. David will begin on Wed Oct 22. He’ll continue to be at home, with frequent outpatient visits. The cabozantinib is taken as a pill.

The way to think about this is that we have the gift of time to be with David for a while longer, especially this next little while when he’s feeling well. I’m focusing on this.

Accepting that David’s time with us could be short does not mean we’ve closed our hearts to the possibility of a miraculous cure. The experience of going through the past seven months with David and this illness makes me feel God’s closeness more, not less. God has his purposes and as a result our lives have purpose. I am more content than I have ever been to trust God with my own life and with David’s life. I am praying for David to be healed and if he is healed I won’t be all that surprised. At the same time, I am slowly getting ready to say good-bye, for now, to my son.

Here’s the email David sent to our families this morning:

            “You should probably sit down again. My doctor concludes that my chances of recovering from leukemia are extremely low. I probably have on the order a few months left to live. I am unsure what to think of this. I definitely haven't been overwhelmed by negative thoughts at this news, which is good.

I love you all

David”

            (Mary here) I went to the temple yesterday, to calm my troubled heart. In the temple ceremony, there is always a prayer for people in especial need. The officiator says a prayer aloud, which is never planned or rehearsed. Although he doesn’t know me, and has no knowledge of my situation, he was inspired to ask Heavenly Father for something I greatly need: strength for me as David’s caregiver. I feel great comfort in his heartfelt prayer.

            And I continue to feel great comfort in the love and prayers you have all offered and continue to offer. Thank you!

Blasts Are Back

            I knew it was going to be bad news when Faye at Cox 1 in Mass General called at 10:45 a.m. to ask if we could come an hour early for another echocardiogram. Back in August, when they discovered the relapse, Dr. Fathi told us that David wasn’t eligible for any clinical trials because of his low heart ejection fraction. (One of the first chemo drugs he was given, daunorubicin, probably damaged his heart.) So, the only reason he would order another test right now would be if the latest round of conventional chemo and the DLI (donor lymphocyte infusion) had not been successful. Well, they weren’t.

            The October 6^th bone marrow biopsy showed 16% blasts.

            So, today, instead of seeing the transplant doctor, Dr. Chen for news about the DLI, we’re back to Dr. Fathi, the cancer doctor. He was very sympathetic when he delivered the news. He outlined the current options, both conventional treatments and clinical trials. He sent us home with two thick packets of description of and consent forms for two possible clinical trials. Jim, David, and I will meet with him on Wednesday to discuss the matter, once the latest EF (heart ejection fraction) is known.

            The good news is that most likely the treatments would be outpatient, requiring two office visits a week, after a 9 hour initial screening. The bad news is that the potential side effects are very serious, and the expected success rate not high.

            Our New England Railroads trip was a complete success. Jim and I thoroughly enjoyed all the interesting people we met and the classic railroads we road, including a dinner train ride in Lincoln, NH and a luncheon aboard the Cape Cod Central Railroad. Both featured delicious meals, white tablecloths, and beautiful fall scenery.

            The greatly anticipated ride along the famous White Mountain Kancamagus Highway did not disappoint. The fall colors were at their peak, the coach ride smooth and relaxing. I felt a bit of anxiety on the Cog Railroad ride up the steep, stark landscape to the summit of Mount Washington, but kept myself entertained on the way down by watching the steel roller between the engine and the passenger car. They aren’t connected at all. The operator explained that we did not want to be pulled downhill by a runaway engine. He expressed great confidence in the car’s braking system, and I decided to marvel at the engineering wonder and enjoy the ride.

Neutrophils Continue to Recover

            The answer to my therapist’s question yesterday, “What’s happening?” was “Nothing.” He pointed out to me that after the 6 months we’ve had, that is great news. It is, but the waiting for news is exhausting.

            David has recovered from the high dose cytarabine chemo. He’s nowhere near the level of an active Army medic, but we’ve revised our metric over the past half year.

David’s white blood count (WBC) has continued to rise:

September 18: .7

September 22: 1.3

September 25: 1.6

In about a week, if the neutrophils, first responders of the immune system, continue to increase, they will do another bone marrow biopsy. Then we’ll wait for the results to come back.

            The molecular results from the last biopsy showed no AML-ITD, the original mutation found at the end of March. AML-TKR (tyrosine kinase receptor) and RAS are now present. If remission has not been achieved by the donor lymphocyte infusion (DLI), which was performed September 11^th, we’ll see what our options are. Admission to a clinical trial requires a higher ejection ratio, which would indicate that his heart is continuing to recover from the daunorubicin chemo back in April and May.

            In happier news, Jim and I are going on a Road Scholar tour, “New England Railroads”, for a week, starting Sunday evening. We’ll hear lectures from local historians and ride old-fashioned railroads in Connecticut, Vermont, New Hampshire (to ascend Mount Washington on the famous Cog Railroad), and Cape Cod. Since fall colors move down from the north, we’ll travel from Connecticut, where the first reds and oranges are just appearing, to the famous Kancamagus Highway in the White Mountains of northern New Hampshire. I’ve always wanted to experience that road in the fall, and we’ll be in a “motor coach”, with no driving duties at all. On NewHampshire.com the report for September 24 was that “the colors are really beginning to pop”.

            Thank you to all our friends who have volunteered to be “on call” in the unlikely event that David needs medical care in our absence, both during our whirlwind drive to Perrysburg, Ohio, last weekend and this New England trip. We’re grateful for everyone’s love, support, and prayers.

Leukemia Still Detectable

            I was quite disheartened last week, and struggled unsuccessfully to post, but there is some positive news today.

           

Last week’s report:

On Thursday, 11 September, we got the disheartening news: despite the high dose cytarabine chemotherapy, leukemia was still detectable in the bone marrow biopsy on Monday, 8 September. The marrow is “hypocellular”, meaning there aren’t many cells, thanks to the chemo, but some of them are leukemic blasts. Blast!

            Dr. Chen said, he wasn’t happy with the results, but we’ve still got options.

            So, on 11 September, David received a dose of Sam’s lymphocytes, collected in August. Hopefully these lymphocytes will stimulate the previously transplanted stem cells.

The technician rolled a metal cart into the room, which held a covered 2 gallon turquoise toy garbage can, and a large metal machine the size of our desktop printer. Wisps of nitrogen vapor swirled, as he removed the small plastic bag from the bucket. The fuchsia-rose-colored blood came into the room at negative 85º C. Placed into the warming machine, the bag was body temperature in just a few minutes. The infusion into the port in David’s chest took about 10 minutes. Dr. Chen looked in afterwards. “I missed the main event!” Dryly David replied, “It was really exciting.”

Stored at negative 170ºC, the lymphocytes have a 10 year expiration date. They were able to harvest 2 doses from Sam. They may infuse the second dose in about a month.

            Over the weekend, David was able to go with us to Carl and Susan’s second home in the Poconos (northeast Pennsylvania). We spend a drizzly Saturday in their cozy house, talking, watching a movie, and eating the delicious food Susan prepared. Also drinking diet white birch beer soda. Why doesn’t Massachusetts have white birch beer? Does any place other than Pennsylvania offer such a delicacy? On our emergency ice cream trip to the Weis Market we picked up 3 cases to bring home. Come on over and try some.

[I’m polling the group: 1) Have you tasted birch beer soda, of either the white or red sort? 2) Can you buy it locally?]

Back to today, 18 September 2014:

            It’s Day 25 from the start of the high dose chemo. David’s white blood cell counts have started to rise, from a steady .1 (practically zero: the target range 4.5 to 10.), to .7. We hope he recovers (a 2 will be acceptable) by day 35.

            His platelets and red blood cells have started to recover as well: today he didn’t need a transfusion of any kind. The platelets were 6 on 15 September and 21 after a transfusion on that same day. Today they are 23, which indicates his bone marrow has restarted production.

A Fast for David

              We spent a quiet Saturday at home. David continues to eat and is in good spirits. His eyes were very sensitive to light yesterday, and today he still couldn’t read his iPod. High dose cytarabine has known ocular side effects. He was prescribed eye drops for the first few days after chemo; he resumed using them yesterday.

            On Friday his white blood count was .2 (happy range is 4.5 to 10), up from .1 a few days before, but still very low. His platelets were also low, which increases the risk of bleeding. Jess Driscoll, the nurse practitioner, wanted to give him aplatelet transfusion, but the MGH blood bank was low, and so she sent us home with the warning not to play with any knives. He’ll probably receive platelets Monday.

            On Monday, Jess will perform another bone marrow biopsy. The preliminary results take about a week. We hope for no detectable leukemia blasts. The situation is grave. On August 15^th, Dr. Fathi told us that if David were an older man, no further treatment would be recommended. Since David is young and relatively strong, he was willing to try a round of high dose cytarabine. Now we wait to see if it had the desired effect.

            Our church congregation (the Arlington Ward) and the Cambridge Stake leadership are dedicating their monthly fast to David’s health and to give strength and comfort to our entire family. I know our Heavenly Father lives and He loves us. If it is the Lord’s will, faith, prayers, and fasting can call down great blessings and even miracles from heaven. Please join us in this prayer.

Day Ten, Back in Lexington

David came home from MGH five hours ago. The oncologists wanted him to stay in the hospital, since his white blood counts are extremely low: they fully expect him to have an infection and they’d prefer he was in the hospital with immediate access to antibiotics. However, David was insistent, and I promised to bring him back to the hospital at the first sign of fever. Once outside, he walked briskly to the car, which was wonderful to see. His nausea has abated and he’s able to eat food!

           This morning, before he left Lunder 10, he had two transfusions: red blood cells and platelets. He will return to Cox 1, the outpatient clinic, on Friday and again on Monday, to monitor his blood counts, and possibly have more transfusions.

            In negotiating for his release, we learned from the oncologist that although clean habits at home are good, the greatest risk of infection is from the normal bacteria that live in his gut. Not much we can do about that, except frequent hand-washing.

            For my part, I thoroughly cleaned the house. It may not matter much, but it is the one thing I have control of. Annie told me of a very difficult time on her Taiwan mission. Everything was hard. So, she stood by her air conditioning thermostat and switched it on and off. On and off. She could control that: on and off. For me it’s cleaning and food safety. I can do that.