Before telotristat

Octreotide and Lanreotide have been the go-to drugs for patients with NET cancer’s carcinoid syndrome for the last several years. They work by blocking the receptors on the tumors that cause them to secrete serotonin. Serotonin causes the symptoms carcinoid syndrome patients face: flushing, insomnia, diarrhea, bloating, and light-headedness, among others.

…I am not a doctor…

In some respects, the most immediately concerning of the most common symptoms are those involved with the digestive tract. The bloating leads to a loss of appetite; if you feel full, you don’t eat. If you don’t eat, you lose weight. When you do eat, the syndrome pushes the food through so fast there is no time to absorb the calories, let alone the trace elements, the body needs to function.

Syndrome creates social and physical issues

Frequent diarrhea–think several episodes a day, every day–also does bad things to the patient’s social life, as well as mental health. A life governed by how closeness of the nearest bathroom eventually leads patients to just stay home.

They work by blocking the receptors…

In the longer term, the excess serotonin causes a fibrosis of the intestines, destroying them the same way it destroys the valves in the right side of the heart. That fibrosis compounds the digestive problems by making it even harder for the intestines to absorb the nutrients the body needs to survive.

Somatostatin analog issues

Octreotide LAR and Lanreotide are long-acting somatostatin analogs. They were a big step forward over daily injections of the initial form of Octreotide. That form now gets used largely as a rescue drug for when symptoms return between the monthly injections of the longer acting drugs.

Frequent diarrhea–think several episodes a day, every day….

Unfortunately, for reasons that are not well understood, none of the somastatin analogs works for everyone. And they may eventually stop working even in those patients who have a positive response.

Telotristat: a different approach

Enter telotristat ethyl, a drug that comes in pill form that inhibits the production of tryptophan hydroxylase (TPH). Tryptophan–the infamous stuff in turkey meat that supposedly is the cause of Thanksgiving naps–is one of the things you must have in order to make serotonin. Slow–or stop–the creation of tryptophan and you slow the creation of serotonin.

…none of the somastatin analogs works for everyone.

A  of telotristat involving 135 patients showed that, “Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with telotristat ethyl  was generally safe and well tolerated and resulted in significant reductions in BM (bowel movement) frequency and urinary 5-hydroxyindole acetic acid (5-HIAA urine test).” (Items in parentheses added for clarity.) Doctors use the 5-HIAA urine test as a means to measure the amount of serotonin the body produces by looking at a by-product of it being metabolised in the liver.

Finding the right tool

We’ve known since 1967 that inhibiting TPH could improve symptoms for carcinoid patients. But previous drugs that would do that crossed the blood-brain barrier and resulted in patients becoming depressed. Too little serotonin in the brain is just as bad as too much elsewhere, it turns out.

…the infamous stuff in turkey meat…

Telotristat, for a variety of reasons, doesn’t cross the blood-brain barrier. Some patients did experience depression while using telotristat, but it was not clear, based on the results of this study, that the incidence was any greater than that of the patients in the placebo arm. It ?????????????????????????????????????????????????????????????????did not cause them to drop out of the study.

Telotristat impact

At the start of the study, the mean number of bowel movements per day ranged from 5.2-6.1. For the average patient, that number decreased by nearly three BMs per day–essentially cutting the number of BMs in half for many patients.  5-HIAA urine levels also showed a dramatic decrease: 78 percent of patients saw 5-HIAA levels decrease by more than 30 percent.

…doesn’t cross the blood-brain barrier.

The study did not look at fibrosis in either the intestines or heart but suggested, given the dramatic lowering of 5-HIAA levels, that a future study look at that.

Telotristat side effects

With any drug, there are potential unwelcome side-effects. We’ve already mentioned depression. Some patients experienced some increases in liver enzymes, while others experienced nausea. Neither was at a level that caused patients to drop out of the study, but longterm follow-up of these side effects is planned.

…essentially cutting the number of BMs in half…

Based on the results of this trial, the drug went the FDA for approval in the US and for approval in Europe.

A step forward

Having watched Jane inject herself with octreotide twice a day after her diagnosis–seemingly to little effect–I’m all in favor of oral medications whenever possible. Octreotide certainly did not control her symptoms. This absolutely looks like a significant step forward to me.

We’ve already mentioned depression.

But there are some other things to keep in mind: I am not a doctor and none of the above constitutes medical advice. I’ve read the paper and have run this by my friends at Dana-Farber to make sure I haven’t badly messed up in putting this in layman’s terms, but you really need to talk to your doctor about this, or any other treatment.

(Editor’s notes: The text of the original paper as it appeared in the Journal of Clinical Oncology can be found here. My thanks to Matt Kulke at the Dana-Farber Cancer Institute, lead author of the paper, for his help in making sure I’ve got it all right, medically speaking.  

(The last two posts in the ongoing 30 Day Challenge were not posted to many sites as they did not address anything patients or lay caregivers generally need to be concerned with. If you want to see them, they can be linked to from our Facebook page or on the NET Cancer News menu, where they appear in the order they were written.)

(This post is going up a day later than planned because of a commitment I had to take a friend to Boston. That ended up a 14-hour day and I was just too beat to want to do more than stare at a TV screen for a bit when I got home.)

(The post scheduled for today will go up sometime tonight.)