Take-home Message

Dealing with the therapeutic index of interventions

(Fictional narrative by the doctor)

James Fleck, MD, PhD: Anticancerweb 24 (02), 2020

On the scheduled date, Milton returned to the clinic, starting adjuvant treatment. He was fine, the surgical wound was healed and his nutritional status returned to normal. The previously detected anemia disappeared and all hematological counts and biochemical assessments made him eligible for adjuvant treatment.

The first phase would consist of five days of outpatient chemotherapy. Milton didn't show much curiosity, feeling confident as always. He came along with Doris, who would accompany him throughout the treatment. I explained that this phase would probably not generate adverse reactions. Even so, we would keep him under surveillance. He would receive medication to protect against vomiting followed by intravenous chemotherapy. He would have to stay at the clinic for about one hour a day. Although chemotherapy was administered for only five days, its biological effect would continue for the next three weeks, which would explain the interval preceding the second cycle of chemotherapy.

Milton would also have to make an appointment with the radiation oncologist, as his treatment would require a combined approach including upper abdominal irradiation, starting with the second cycle of chemotherapy. Using sophisticated software, the radiation oncologist would define the dose, involved-fields and the schedule for Milton's radiation therapy. 

I also explained that there were rare situations of deficiency of dihydropyrimidine dehydrogenase (DPD), an enzyme needed in the metabolism of fluorouracil, the main chemotherapy drug used in Milton's adjuvant treatment. This is an autosomal recessive disorder, leading to severe and even lethal toxicities after using any fluoropyrimidine. I had already requested an enzyme DPD assay and, fortunately, Milton's value was within the normal range.

Our head nurse, with over twenty years of experience, accommodated Milton and Doris in a chemotherapy room. Doris brought an embroidery and started working on it, giving Milton a sense of serenity. He, of course, carried a laptop.

After starting intravenous chemotherapy, Milton returned to his cloud computing project, a subject that seemed to interest him more than cancer treatment. He had advanced in the Global e-PHR software, but he still needed to share some risks and pitfalls with me.

He said the heart of the project was in patient self-management of Global e-PHR. He had informally sought legal advice from experts at his company, but apparently medical IT legislation was still fragile.

Milton was concerned about data security and was trying to impose some additional control devices. He remembered the missed exams and said that this should never happen on the new electronic system. Milton had designed a system as secure as those used by banks.

I expressed my contentment, but asked him to continue to see this project as "occupational therapy" and not to put too much negative stress on it.

Milton interrupted me and asked what I meant by negative stress.

I responded as any inducer of emotional distress.

He answered by saying that he was conducting this project with great enthusiasm. He was not putting himself under pressure. Staying focused on the software was helping him to deal with cancer treatment.

I explained that all the challenges we face in life could include gratification and suffering. I asked Milton to always share his emotions with me so that we could analyze and overcome them together and, eventually, avoid them.

Returning to the subject of his preference, he asked me to think about the set of behavioral changes that this project would require. He warned that it was a very futuristic idea and that we needed to imagine how this new reality would be received by the health care system.

He suggested implementing a pilot project at the clinic to assess its functionality. Patients would be informed and would participate voluntarily.

I promised him that I would think and that we would soon return to this subject.

Milton went through the first cycle of chemotherapy without complications and his radiation therapy had already been planned.

He has established a very good relationship with the professionals in the radiation therapy department, being very interested in image-guided radiotherapy (IGRT) and respiratory gate software. These technical improvements increased the safety of the treatment, as they provided greater definition of the fields to be irradiated, reducing the exposure of normal tissues to undesirable radiation. The respiratory gate allowed intermittent operation of the device, based on breathing movements of the chest and upper abdomen wall.

Milton started the combined phase of his treatment. Chemotherapy and radiation therapy would enhance each other's effect, increasing the mortality rate of cancer cells. However, combination therapy also used to be associated with more adverse events.

Two weeks after the beginning of radiotherapy (RT), Milton started with a loss of appetite followed by intermittent and uncomfortable pain located in the upper abdomen. Despite these complaints, RT had to be continued, providing the required dose intensity in a gastric cancer treatment with curative intent. The benefit of irradiation depends not only on the total dose, but also on the schedule, giving the entire treatment within the planned five weeks. By the end of the fourth week, Milton had improved somewhat, despite the cumulative dose of radiation administered. He said that, fortunately, radiation was administered only five times a week and that the planned breaks by the end of the weeks had been essential for his recovery. 

During the last week of RT, Milton would face the radiosensitizing effect of three additional days of chemotherapy.

Milton had a hard time coping with this phase. He felt prostrate and completely lost his appetite. Severe mucositis in the mouth and esophagus required hospitalization. He had nausea, vomiting, diarrhea and increasing abdominal pain. He received intravenous fluids and electrolytes, as well as nutritional support. Anemia intensified, followed by a drop in white blood cell count. However, there was no sign of infection. Anemia reached a critical value requiring a transfusion of two units of red blood cells. Milton progressively improved, being discharged from the hospital in a few days. I kept him under frequent control. He used to call me once a day. 

Two weeks passed and he came back for consultation.

He was much better. His symptoms were minimal and he had a more favorable nutritional status. He admitted that he underestimated the risks expected for this combined treatment phase. He asked if the next two cycles of chemotherapy would be equally difficult.

I said, probably not. I explained that the most difficult phase was the previous one. Even a month later, chemotherapy could eventually cause a relapse of radiation side effects, but even under this circumstance, it would not be as toxic as in the concomitant treatment phase.

Milton was relieved.

Speaking quietly, he confessed to having temporarily stopped working in the cloud, but that he was looking forward to returning to the Global e-PHR project asap.

I mentioned that this was an important project with significant humanitarian value. A progressive digital inclusion was in line with his vision. Most health care would be based on interactivity. Global e-PHR project has contemplated the most important interfaces in the relationship of patients, doctors and institutions.

I reminded him that everything started with his negative experience with an unqualified health care provider who lost his exams. However, it allowed him to promote one of the most relevant ethical aspects of medicine…

For a few seconds, Milton stared at me with a surprised and questioning expression!

He may not have realized this, but his Global e-PHR software gave the patient self-management of his medical record, according to his needs and rights. 

Milton completed his treatment successfully and resumed his activities at the company, gradually assuming higher responsibilities.

Today, Milton has reached two years of follow-up. 

Clinically stable, he shows no signs of relapse. 

He carefully follows all my recommendations. 

We continue to improve our ideas and functionalities on Global e-PHR project.

Presently, our most important challenge is dealing with necessary human behavior changes.

To be continued in PLOT 6 (resolution) …

* Attention: The story 5 will be published sequentially from PLOT 1 to PLOT 6 and you will always see the most recent posting. To read Story 5 from the beginning, just click in the numbered links located at the bottom of the homepage. 

© Copyright 2020 Anticancerweb

 James Fleck, MD, PhD: Full Professor of Clinical Oncology at the Federal University of Rio Grande do Sul, RS, Brazil 2020 (Editor)