New Treatment

When I last checked in, I'd just gone back home from New York. I put treatment on hold while my doctors, my family, and I investigated treatment options. There is no standard second-line therapy for Ewing's sarcoma. Rather, different doctors and hospitals have their own protocols. Sloan-Kettering used to use irinotecan and temozolomide as a second-line treatment. Now that they use these drugs as part of first-line therapy, they've switched to cyclophosphamide and topotecan. Some places, though Sloan is not one of them, if second line chemotherapy produces a response, proceed to high-dose chemotherapy. High dose chemo involves giving a dose large enough to wipe out a patient's bone marrow. To counteract this, stem cells are first harvested from the patient, that are then given back after the chemo has had its effect. High dose chemo is often a first line treatment for metastatic Ewing's in Europe.

This goes to show that there's no consensus on what to do in metastatic and recurrent Ewing's, which is difficult to treat. In my case, with the multiple lung spots and my having already had irinotecan, Dr. Meyers was concerned that combining the related drug topotecan with cyclophosphamide, another drug I've already had, wouldn't produce a satisfactory response. So we started exploring clinical trials, where a particular treatment that has not been used before is tested for safety and effectiveness. During this time, I couldn't get any treatment. Clinical trials have strict eligibility criteria that treatments can easily violate. Blood tests have to fall within certain parameters. There needs to be a gap of at least the cycle length between a chemo administration and starting treatment. Major surgery also requires a recovery period before treatment can begin.

Immunotherapy, in which the immune system is stimulated to attack tumors, was the theme. The immune system normally plays a big role in attacking cancer cells and keeping them from turning into active disease, but as these cells mutate rapidly, they can find ways to evade the immune system and establish themselves. One popular immunotherapy approach involves using vaccines to train the immune system to recognize tumors as foreign. Another involves counteracting defenses cancer cells evolve to escape destruction by the immune system. The trial we ended up focusing on uses the second method. The specific approach is called checkpoint inhibition. Cancer cells can put the brakes on the immune system by displaying what are called immune checkpoints that tell the immune system not to attack. Immune checkpoints are used by the body to prevent autoimmunity, where the immune system attacks the body itself, but cancer cells can make use of these to evade destruction.

Checkpoint inhibition is already used to treat advanced melanoma, with the FDA having approved multiple drugs that block immune checkpoints. Melanoma is not very responsive to chemotherapy or radiation, so checkpoint inhibition represented a major advance in treatment, and some patients have seen dramatic responses. Clinical trials are now underway to evaluate the effectiveness of checkpoint inhibition in many other cancers. The one I'm in uses a drug called pembrolizumab (trade name: Keytruda). It is open at multiple locations across the country. The closest to me is at the University of Southern California in Los Angeles, a 5-6 hour drive. The treatment is once every three weeks, 30 minutes by IV. There are side effects, but much less than chemo. Common ones are fatigue, diarrhea, and cough. Obviously, I'd prefer to be closer to home, but trips to LA once every three weeks is minimally disruptive compared to how things could have been if I were to get chemo or this same treatment farther away where the only option would have been air travel. I also have family there, so I won't be alone when I come in.

The preliminaries began with an initial consultation on May 5th. Then there was a CT scan of my chest, abdomen, and pelvis to establish a baseline. Thankfully, the tumors have not spread to any other organs, but I've gotten new ones since my last scan, and the existing ones have gotten quite a bit bigger, so I couldn't have waited much longer. This week, there was a needle biopsy on Wednesday to obtain a tumor sample. Another sample will be taken at week 8 to evaluate response to treatment. Then, there was more blood work. Finally, on Friday, I received my first treatment. I will be getting two more for sure. At week 8, there will be another CT scan to evaluate response. Tumor growth greater than 20% or new tumors will be counted as disease progression, at which point I'll be off the trial and will have to find another treatment option. Subsequent scans are taken every 12 weeks.

The first IV bag being hung.

I really hope this treatment works. So far, the only side effect I've felt was some fatigue yesterday. I expect to be able to live a normal life, unlike when I was getting chemo. This makes me very happy, but even so, I am quite nervous. The thing about chemo, as brutal as it is, was that I knew it was doing something to me. How couldn't I with all those nasty side effects? To be fair, that is no guarantee that the chemo is doing anything to the cancer cells, but there is something to be said for perception. With Keytruda, without those side effects, how can I tell that it's doing something? I guess the proof will be in the pudding. If I become symptomatic or start feeling extreme pain somewhere, then I know it's not working, but if I stay asymptomatic, I have reason to be encouraged. A real-life example of the saying, "No news is good news." So, outside of side effects, here's hoping I stay free of symptoms!