Jodie Barr, DO, hematologist/oncologist, Lawrence Memorial Hospital, discusses the combination of temozolomide and capecitabine in neuroendocrine tumors (NETs).

Findings of small studies have confirmed the efficacy of combination therapy with capecitabine and temozolomide. Data from NYU Langone Health has suggested that the combination has an important cell-directed cycle effect on tumor cells.

In a study that examined the combination, patients were randomized to either temozolomide and capecitabine or temozolomide. The rationale stemmed from capecitabine’s potential synergistic effect with temozolomide in depleting O

-Methylguanine-DNA methyltransferase, says Barr.

The trial enrolled patients with grade 1/2 disease. The study was not blinded, which served as a bias of the study. Investigators examined progression-free survival (PFS) as the primary endpoint and found a significant benefit in PFS with capecitabine and temozolomide. The interim analysis showed hints of benefit in overall survival as well, says Barr.

Although its efficacy has been proven in a number of small studies, the combination regimen is more complex. Patients must take 1 of the drugs 2 out of the 4 weeks and the other drug every 10 to 14 days.

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Dr. Barr on Temozolomide and Capecitabine in Neuroendocrine Tumors

Jodie Barr, DO, hematologist/oncologist, Lawrence Memorial Hospital, discusses systemic therapies for patients with neuroendocrine tumors (NETs).

Therapeutic options for NETs have been limited in the past, says Barr. There is a lot that physicians do not yet know about the biology of these tumors, as they are a very heterogeneous group of malignancies.

The E2211 study looked at the combination of capecitabine and temozolomide (Temodar) compared to temozolomide alone. The trial serves as a foundation for future confirmatory studies, especially for those patients with more aggressive disease, says Barr.

The NETTER-1 trial looked at Lutathera (lutetium Lu 177 dotatate). The agent was initially studied in midgut NETs and showed a significant response rate and decreased the risk of death by approximately 79%. The results of the trial have armored physicians with another treatment option to combat the disease.

Telotristat ethyl (Xermelo) has helped with symptom management, especially for those patients with refractory diarrhea. Genetic sequencing has also furthered the standard of care in an effort to further personalize medicine, states Barr.

Dr. Barr on Systemic Therapies for Patients With Neuroendocrine Tumors

I can remember waiting anxiously on match day; checking the computer every few seconds to see if I matched. The results were in… I got in!

Feelings of excitement and accomplishment overwhelmed me. I received hugs from my program director and faculty. After 3 years of residency, and another as chief resident, I was happy to have made everyone proud.

That night, after the excitement waned, a feeling of anxiety set in. Thoughts of moving to a new city 9 hours away from home, along with the fact that I was pregnant with my first child, were a little overwhelming.

Things became very busy and fast paced. I tried to do the best job I could as a chief while I began looking for a place to live and preparing for my first day of fellowship.

Before I knew it, all of our belongings were loaded into a truck and my new endeavor was beginning, ready or not. I felt a multitude of emotions as my husband and I pulled away from our home with a 2-month-old child, our Boston terrier, and Grandma and Grandpa, who thankfully helped us move. I felt torn as I considered leaving with the first grandchild in my family in 19 years and pursuing my dream that I had worked so hard for. Thinking, though, of the incredible opportunity that I would pursue kept me going through that long drive.

During my first day of fellowship, I thought that I was having palpitations as I walked into the cancer center. So many things were going through my mind.

“Wow this is so cool that I’m here! What will my colleagues be like? Will I be able to live up to the expectations set by the program? I already miss my little one!”

As I walked into the conference room, I was welcomed by my colleagues and program director.

This eased my fears a bit. Orientation went smoothly and I thought to myself, “OK, I can do this. No problem.” But then, the palpitations came back. I was told by the chief fellow that I had to go see consults on my first day, and then I had to attend my first continuity clinic. My pager started to beep! Three new consults. After a deep breath I thought, “Well, here we go!” I worked my way through the consults as best as I could and then headed to clinic.

My first patient in clinic was an incredible gentleman with extensive-stage small cell lung cancer. Once again, I felt those palpitations as I walked into the exam room. I thought, “Please don’t ask me anything! Or maybe just ask me something internal medicine—related…I can answer those questions.” After speaking with my patient and meeting with his incredible family, I felt a comfort knowing that I had made the right decision.

So, I made it through the first week. Then through the first 2 months. After this came the call for a bone marrow biopsy. I had practiced a few as a resident, but was definitely not confident in my skills. Again came those palpitations. I was very fortunate as the gentleman that I was to do the biopsy on had had several prior. He practically talked me through the procedure. Meeting this amazing gentleman reminded me again that I was in the right field.

I was finally in the groove of things when my first call came along. I thought, “No problem, I can handle this.” After 3 years of internal medicine residency I thought I was a pro. Well, I was wrong. Call-in fellowship was much different. Taking calls from home was a whole new ball game. I felt scared out of my wits, especially receiving calls from patients that were incredibly sick. Each time, I hoped I had made the best decision for the patient. I probably drove my fellow colleagues and attendings crazy with questions. Although I have slowly gained confidence in my decisions, I admit that I still need some help here and there.

After all of these firsts, I have learned a few things that have helped me through each situation. Here are a few tips for getting through your first 6 months of fellowship:

		Take a deep breath before you pass out. Everything will be just fine!

		Ask questions. No questions are stupid! It’s better to ask than to have a bad patient outcome.

		Read as much as possible, even though this is difficult as a first-year. Try to set aside at least 20 minutes a night to read about a patient you saw that day.

		Learn the basics and the studies that led to them, and then build upon those with new studies.

		Take time for your family. Set aside all the things that you have to do for those important moments, because you are where you are thanks to their support.

		Embrace your patients. You will learn more from them than any books you can read.

		Support your colleagues. They will have your back when you need them most.

		Don’t be discouraged. You will face more challenges than you have ever dealt with before. Face them head on with confidence.

		Set time aside to decompress, especially on the day when you lose your first patient to cancer.

		Finally, enjoy the journey. Soak up as much as you can in your 3 years and go forward in your career with a fierce passion and love.

All in all, my first 6 months of fellowship have been a whirlwind of emotions. From learning how to balance work and family, especially with a new little girl—to learning what a specific translocation for acute myeloid leukemia means for prognosis&mdash;to supporting my patients through the most difficult time they have ever faced&mdash;it has been an incredible journey thus far. I wouldn’t have asked for any career path other than this!

Jodie Barr, DO, is currently a fellow at University of Kansas Medical Center.

Articles

I can remember waiting anxiously on match day; checking the computer every few seconds to see if I matched.

Jodie Barr, DO

Articles

Dr. Barr on Temozolomide and Capecitabine in Neuroendocrine Tumors

Dr. Barr on Systemic Therapies for Patients With Neuroendocrine Tumors

Life as a First-Year Fellow