MEK 162 and BYL 719 Combination Clinical Trial

             Another long day at Cox 1. David started the clinical trial of two drugs, MEK 162 and BYL 719, that hopefully will work in tandem to stop the signaling pathway in the RAS mutation cells, which David has had since August. It will probably take a few weeks for any positive results to manifest (if they are successful), but, except for study blood draw days and bone marrow biopsies, he can be on hydroxyurea and stay in the study, which is a relief. Hydroxyurea won’t lead to remission, but it keeps the leukemia at bay for a while, where nothing else has been effective.

 MEK inhibitors have been used successfully in “solid tumor” cancers, such as melanoma and breast, lung, and colon cancer. This study is researching its effectiveness in RAS mutation leukemia, where the ‘tumors’ are the single leukemic white blood cells.

            For those of you with more biochemistry background than me, here’s an excerpt from the very short Wikipedia article:

A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers. (See MAPK/ERK pathway#Clinical significance.)

The hope is that the study drugs will change the “signaling pathway” where the signal for cell division gets stuck in the ‘on’ position. In some cancers, including leukemia, the cancer cells don’t get the signal to stop cell division, so they continue to divide uncontrollably and take over.

An observation about the effect of hydroxyurea on the WBC count, by comparing December to April:

The first time David’s counts skyrocketed, the hydroxyurea lowered the WBC count from 95 to under 4 in 7 days. The percentage blasts also dropped, from 76% to 44%.

Date of Blood Draw (CBC)	White Blood Cell Count	% Blasts in circulation	Hydroxyurea dose	Note on hydroxyurea dosage
2-Dec-2014	91.51	76.0%
3-Dec-2014	95.27	72.0%	2g/day
4-Dec-2014	76.39	75.0%	4g/day
5-Dec-2014	42.78	72.0%	6g/day
8-Dec-2014	8.20	59.0%		Lowered dose-WBC were down
10-Dec-2014	3.84	44.3%		Stopped hydroxyurea

However, in April you can see that the hydroxyurea hasn’t been as fast acting and only lowered the WBC counts below 11 briefly. The percentage blasts, after hovering between 69% and 88%, have increased into the 90s, even on 5 and 6 grams of hydroxyurea per day.

Date of Blood Draw (CBC)	White Blood Cell Count	% Blasts in circulation	Hydroxyurea dose	Note on hydroxyurea dosage
14-Apr-2015	66.95	74.9%	4 g/day	start 11 a.m.
15-Apr-2015	67.68	88.5%	4 g/day
16-Apr-2015	47.07	72.8%	4 g/day
17-Apr-2015	35.86	80.5%	4g/day
19-Apr-2015	23.55	84.0%	4g/day
21-Apr-2015	10.67	88.0%	2g/day	Lowered dose for lower WBC
24-Apr-2015	12.39	68.7%	4g/day	Up dose to tank up before  trial
27-Apr-2015	24.42	86.0%	1g in p.m.	Back on hydroxyurea after biopsy
28-Apr-2015	--------	--------	2g/day in a.m.	Off of hydroxyurea for clinical trial
29-Apr-2015	50.79	90.0%	4g/day	Hydroxyurea: trial postponed.
30-Apr-2015	42.27	94.0%	5g/day	Raise dose
1-May-2015	--------	--------	5g/day	Maintain dose
2-May-2015	53.72	91.5%	5g/day
3-May-2015	--------	--------	6g/day	Raise dose to "tank up" before trial
4-May-2015	43.88	94.0%	6g/day	Took dose in p.m., after study started

            In other news: Matt visited for the weekend, which put us all in a good mood. He successfully kept Jim, who turns 60 this week, occupied in his coachhouse office behind the house, so that I was able, with some much-needed help from Autumn, to make a meal and quietly get 24 people into the house to yell “Surprise!” when he and Matt came through the door. Jim’s brother, Jeff, wrote a song, “Now You’re Sixty and More” to the tune “When I’m 64”, which was my class song at Bryn Mawr. An unforeseen complication was that no one under 58 knew the song (come on, people! It’s classic Beatles!), but our friend Sam saved the day by pulling it up on his phone for our quick rehearsal.

            Jim was totally surprised, which was gratifying. He was out of town last week, so I had time to bake the cake and cook the pastry cream for Boston Cream Pie. While Autumn made our canonical mac&cheese, I made the chocolate glaze and constructed the pie. As a new way to serve it, I made extra pastry cream and chocolate glaze, so we had cake topped with extra cream filling and chocolate glaze plus vanilla ice cream on the side. Hope I can still get into my dress for Sam’s wedding.