The carcinoid syndrome problem
Carcinoid syndrome sucks. I know. I watched Jane wrestle with it for years: the flushing, the mood swings, the insomnia, the diarrhea. I watched her inject herself in the belly with octreotide every morning, waited with her for the monthly sandostatin injection to thaw out at the Dana-Farber Cancer Institute.
…patients will still have to face at least a monthly needle.
None of the palliative drugs worked very well for her. Part of that was her cancer was so advanced when it was diagnosed that it simply overwhelmed all efforts to ease her symptoms. Any relief she got didn’t last long. Part of it may also have been the standard treatment doesn’t help everyone.
A new hope–at least for symptoms
But there is new hope on the horizon. The recently finished Phase 3 trial of telotristat etiprate showed the drug has a positive impact for “patients with carcinoid syndrome that is not adequately controlled by the current standard of care” according to a release last week from the drug’s developer, .
None of the palliative drugs worked very well for her.
The TELESTAR Phase 3 trial of the oral treatment was directed by Dr. Matt Kulke’s group at DFCI. If and when the FDA approves telotristat etiprate, it will be the first new treatment for NET cancer patients suffering from carcinoid syndrome in 16 years.
Quick action possible
According to Kulke, that approval could come within a year of the drug’s officially being submitted to the FDA. Because NET cancer is considered an orphan disease, new drugs for it get expedited treatment at the FDA.
…there is new hope on the horizon.
The study added telotristat etiprate to the current standard of care for a group of carcinoid syndrome patients who were not getting much relief from that standard. With both 250 mg and 500 mg doses, the patients “experienced a statistically significant reduction…in the average daily number of bowel movements over the 12 week study period” compared to those on a placebo, according to the .
Professional reactions
Kulke, who directs the Program in Neuroendocrine and Carcinoid Tumors at DFCI, called the TELESTAR results “promising, and the community of patients and caregivers who live and deal with carcinoid syndrome are excited about the prospect of a new treatment becoming available.”
“…a statistically significant reduction…”
Lexicon president and CEO Lonnel Coats was “extremely pleased” with the results of the trial. “We are committed to working closely with the FDA to file our…new drug application and to bring this innovative new treatment to patients whose lives are already impacted by the challenges of cancer.”
By the numbers
The release does not go into many details about the results of the trial, however. Those will be released at a conference in Vienna in late September. But it does offer a few glimpses from which patients and caregivers can glean some idea of the drug’s potential impact.
“We are committed to working closely with the FDA…”
The study defined a durable response as “at least a 30 percent reduction in daily bowel movements over at least half the days of the study period. Forty-four percent of the patients on the 250 mg dose achieved that level of relief. Forty-two percent experienced that on the 500 mg dose. Those numbers compare to 20 percent of patients on the placebo.
Side effects
Patients in all three arms of the trial had similar numbers of and types of “adverse events.” The “tolerability profile” with the placebo and the 250 mg dose were similar–and both were somewhat better than the higher dose when it came to mood and gastrointestinal discomfort.
…a 30 percent reduction in daily bowel movements…
The company promises to do “further in-depth analysis of safety and tolerability data.” Patients in the 12 week study are all now on an open label extension for 36 weeks, receiving 500 mg of telotristat etiprate three times a day.
How it works
Telotristat etiprate works by targeting tryptophan hydroxylase (TPH). TPH is an enzyme “that triggers…excess serotonin production within mNET cells.” The excess serotonin is what causes carcinoid syndrome.
…similar numbers of and types of “adverse events.”
It is different from somatostatin analogs, which work to reduce the release of serotonin outside the cells, because it works to inhibit the creation of excess serotonin to begin with. In a nutshell, control the TPH and you control the production of the serotonin that is causing the problem.
What the study doesn’t tell us
But before we get ready to throw away the syringes, we need to be aware the study didn’t try telotristat etiprate on its own. Patients continued with their somatostatin analogs throughout the study. There is no evidence here to suggest how the new drug would do on its own.
…works by targeting tryptophan hydroxylase…
It is possible the combination of the two methods is what caused the results–and it is equally possible only the telotristat etiprate was involved. We won’t know that until–and unless–someone studies telotristat etiprate as a stand-alone treatment.
The monthly needle remains
We also know that octreotide and lanreotide do slow tumor growth–something we don’t know about the new drug. For the foreseeable future, carcinoid patients will still have to face at least a monthly needle.
We won’t know that…
And nothing we have yet offers patients a cure. We can ease the symptoms. We can slow the progress of the disease. We can buy more time together–and more time to find a cure. This seems likely to help accomplish each of those ends.
Thank-you for sharing the details of this study. Much appreciated.
About the monthly shot… I completed the Telestar trial and have been in the Telepath for long term safety and efficacy for over a year. One of the requirements to enter the trial was to be on one of the somatostatin analogues and not have enough symptom control, or to be intolerant of the analogues. I am on Sandostatin LAR. The telotristat has been of great value to me, and helped me in ways the Sando never did. However, I have gotten a few bad LAR injections that just didn’t work. I can attest from that, that the telotristat etiprate on its own was not enough to control symptoms as well during those months as when it was working in conjunction with a good injection. If I have a side effect, it would be my new found heat intolerance. That could just be my age. I’m excited that this drug will soon be available to others, as it has been so very helpful to me.
Thank you for this detailed reply. I suspect others will find it very useful. The current information publicly available does not address what you say here. I wonder if others have had a similar experience.
I will forward your comment to Dr. Kulke, as he may find it useful as well.
–Harry