Cisplatin is a common chemotherapy drug used to treat several types of cancer in both adults and children. While effective, the drug can build up in the inner ear and cause permanent damage. The resulting hearing loss can affect young patients, potentially causing delays in learning and social-emotional development. Until recently, there were few options to prevent or slow that hearing loss. Sodium thiosulfate (STS), a drug studied for years by researchers at Oregon Health & Science University, has been shown to counteract the toxic effects of cisplatin in the inner ear. The FDA has recently approved its use for patients as young as 1 month old.
Kristy Knight, an audiologist at OHSU’s Doernbecher Children’s Hospital, joins us to explain what the treatment could mean for pediatric cancer patients. We also hear from Jennifer Boesche, a Beaverton mother who petitioned the FDA to approve STS after her daughter experienced treatment-based hearing loss.
Note: The following transcript was created by a computer and edited by a volunteer.
Geoff Norcross: This is Think Out Loud on OPB. I’m Geoff Norcross. Chemotherapy can be brutal on a body. The common cancer treatment can cause all kinds of side effects like nausea and fatigue. It turns out, some patients who get a certain drug during their chemo treatments can also suffer hearing loss and that’s a big problem for kids. The Food and Drug Administration (FDA) recently approved a drug that can counteract chemotherapy-induced hearing loss for children. The decision comes nearly 30 years after research into this drug started at Oregon Health & Science University (OHSU). Kristy Knight is an audiologist at OHSU Doernbecher Children’s Hospital and Jennifer Boesche is the mother of a cancer patient who got the drug and got some of her hearing back. Kristy, Jennifer, welcome to Think Out Loud.
Jennifer Boesche: Thank you.
Kristy Knight: Pleasure to be here.
Norcross: Kristy, let’s start with you. Hearing loss is certainly hard for anybody, but can you talk about how it’s especially hard for kids?
Knight: It is hard for children because they’re in the process of developing language and hearing loss results in a loss of information. So the children are not able to hear all of the sounds and words and because they don’t have a fully developed language system and because their nervous system is immature they really can’t fill in those gaps when they don’t hear all the sounds and words and that leads to difficulty understanding the message, delayed speech and language development and significant challenges listening and learning in a classroom setting.
Norcross: So in other words their brains are developing, they’re just not getting the inputs they need in order to develop?
Knight: That’s correct. Yep.
Norcross: The chemotherapy drug that can cause this hearing loss is called cisplatin. Can you talk about how that works and how it affects hearing?
Knight: Cisplatin is a very effective cancer treatment, but one of the side effects is that it can damage the delicate structures in the inner ear that are really critical for our ability to hear. So cisplatin enters the inner ear through the bloodstream. It forms reactive complexes once it enters the inner ear and that damages these sensory cells, like I mentioned, that really account for our ability to hear all the sounds and words and recognize differences and sounds that are important for meaning.
Norcross: Does cisplatin affect kids in this way more often than it does adults?
Knight: It does. Children are more likely to acquire hearing loss during therapy and younger children especially develop more severe hearing loss as a result of cisplatin therapy.
Norcross: Is it kind of the same phenomenon that leads to ear infections with kids?
I mean are they just more prone to getting stuff stuck behind their ear drums?
Knight: It’s actually a different phenomenon, but probably children are not able to detoxify that drug maybe as well or the metabolism of that drug might be different in a young child compared to an older child or an adult.
Norcross: Okay, well now we have this drug that can help that detoxification process. The FDA last fall approved a drug to counteract that hearing loss. And it’s called sodium thiosulfate and we’ll call it STS for our purposes here. How does that work?
Knight: STS is actually given several hours after this cisplatin infusion, but it’s thought that once it enters the inner ear, it is able to bind to those reactive complexes and protect the inner ear tissues from damage.
Norcross: Are there any side effects?
Knight: There are side effects. The primary side effects, as far as I understand, are nausea. There can also be elevated levels of sodium in the blood and so there are careful monitoring protocols that address those side effects.
Norcross: Jennifer Boesche, let’s bring you into this. Your daughter got this drug and we’ll get into how it worked for her in a little bit, but first can you tell us a little bit about Brielle first? What is she like?
Boesche: Brielle is a typical six-year old despite the hearing loss and she is a kindergartner. Now she just started kindergarten and she is spunky. She’s good at advocating for herself. She has a bold personality. She’s very kind with other kids and family and she’s loving.
Norcross: Can you tell us about the time she was diagnosed with cancer?
Boesche: Yes. Brielle was diagnosed at 16-months old and in a pretty traumatic way, which can be pretty common. No matter when you find out your child has cancer. It’s traumatic, but she actually had a fall which ruptured her tumor and caused internal bleeding. And so it wasn’t known at first that that’s what happened. So she was sent home from the hospital internally bleeding all night and then taken back the next morning to discover that she had hepatoblastoma, liver cancer, and her tumor had ruptured in the fall.
Norcross: And so you went on a course of chemotherapy. What was that like for her?
Boesche: It was really rough with the chemotherapy. They determine what type of cancer. Her cancer was determined to be high risk because of the rupture so she had to have one of the strongest protocols, which is four different chemo meds given for that protocol. And so it was months and months of chemo and several surgeries. Her chemo treatment and cancer journey started with a very, very scary peripherally inserted central catheter (PICC) line for several weeks because of the ruptures and the surgeries. And so having to decide to put your child through chemo and such intense chemos is a very difficult decision.
Norcross: Yeah, it sounds like she was dealing with a whole universe of side effects from the chemo. But hearing loss was one of them. Can you talk about how that happened?
Boesche: Yes. When you go over your chemo meds, you’re given information about what side effects can come. And at that time, the study had not been published that was completed regarding sodium thiosulfate. So presented to me at that time was that there were no options to protect her hearing. So they did a baseline hearing test to see if she had any hearing loss. And at the time she did not. She had perfect hearing and I had to do a lot of pushing to have her hearing rechecked.
I had found out about sodium thiosulfate through a Facebook support group for parents of children with hepatoblastoma, but was told that it wasn’t an option at the time. So during her second round of chemo, I’d asked in-patient if I could talk about that and have another hearing test done. They were apprehensive because there was nothing we could do, I was told, even if there was hearing loss, but I spoke with her primary oncologist and he agreed to do another hearing test. So at the start of her third round of chemo, we discovered that her hearing had been impacted by the chemo she had received so far.
Norcross: And you said that STS wasn’t available at the time. You were deeply involved in the process of making it available and you petitioned the FDA to approve it. What was that experience like for you?
Boesche: Kristy Knight was a big help with all of this because she came and talked to me when I found out Brielle had hearing loss and talked to me about the study and I was able to get her team at Stanford and Doernbecher to agree to allow her to use sodium thiosulfate for the rest of the time and Kristy provided them with the study results. And it was scary. When I went to that FDA panel Brielle had only been like a month finishing chemo and all of her treatment. So I was in a pretty fragile place, emotionally as a parent. And it was overwhelming, going and hearing all the effects from other people that their children had suffered from hearing loss and knowing how much she had already and maybe what her future could look like. It was a scary thing to participate in but it seemed really beneficial to be in the place of newly exploring the world of hearing loss with my daughter.
Norcross: Kristy, let’s back up a little bit. I know you weren’t involved in the research on STS that was happening at OHSU, starting I think back in the nineties, but can you tell me more about how it came together?
Knight: I would love to highlight that this was really based on the work of Dr. Edward Neuwelt, Dr. Leslie Muldoon, Dr. Nancy Doolittle and their team at OHSU. Dr. Neuwelt is a neuro oncologist and he primarily treats adults with brain tumors, but he became aware that patients treated with cisplatin were losing their hearing during treatment and really wanted to find a solution to that problem. I think the study of STS was initiated by one of his patients and he and his team really devoted years of study to find if STS was effective and the optimal dose, what the side effects were, how to manage those and the timing of STS relative to cancer treatment so that it could protect hearing without interfering with treatment.
Norcross: And as an audiologist, what has your experience with the administering of STS been? Have you seen an impact on the patients you’ve worked with?
Knight: It’s really clear from the clinical trials that the drug is effective in reducing the proportion of children that acquire hearing loss during cisplatin therapy and also the degree of hearing loss. So it lessens the incidence and severity which is really critical for developing children. And I’d say from my experience–Jennifer mentioned it beautifully–in the past, we knew that hearing loss was a potential side effect and we would work with the family during treatment to identify hearing loss when it occurred. But there wasn’t very much that could be done to change the outcome and this FDA approval and the study of STS really opens a door to changing the quality of life in childhood cancer survivors by minimizing the side effects of the treatment that’s so important in curing their disease.
Norcross: This research started at OHSU some 30 years ago and then there were clinical trials and there was a whole process, but it took about 30 years for the FDA to approve it. It seems like a long time, especially since we’re talking about kids with cancer and hearing loss. Is that a typical turnaround time for a new drug to be approved?
Knight: That’s my understanding that it does take decades. And really the work begins with pre clinical work with different models and then it takes decades before it’s ready to be studied in humans and patients. In the case of children, again, there’s a lot of safeguards around that. And so all of the length of time is related to safety and being as certain as possible as to the anticipated outcomes before the drug has ever been studied in humans. Then once the clinical trials were completed, that led to the process of approval by the FDA.
Norcross: Jennifer Boesche, what was it like trying to get this treatment for your daughter before it was even approved?
Boesche: It was quite difficult. It was shut down immediately when asking about it because of it not being approved. And then unfortunately connecting with Kristy made it possible for Brielle to have it for her last three rounds of chemo. I don’t want to totally correct you, but unfortunately for my daughter, none of her hearing was restored. She actually suffered hearing loss and her hearing loss has been progressive since finishing chemo. She’s gone from mild to moderate to mild to severe, so for her it was a little bit too late with three rounds without the STS was sort of critical for her to permanently damage her hearing.
Norcross: Oh, so if she had gotten this drug earlier it could have made a difference?
Boesche: Yes. I think it could have.
Norcross: It had no effect whatsoever?
Boesche: I don’t know. There’s not a way to know. Did it stop her from having profound hearing loss? I’m not sure. It’s hard to know if it helped. I don’t think I heard anything, but I would have only probably really known had she had it from the beginning to see if it had an impact. Only being able to receive it for half of her chemo rounds, there was already a lot of damage in the first three rounds of chemo.
Norcross: I’m sorry to hear that. Well, how is she doing now?
Boesche: She’s doing really well. She’s had hearing aids since she was two-years old. We put her in early intervention services with a speech therapist. She has a hearing specialist and so being a good advocate for her and utilizing the support; she’s had regular audiology checks and she has been very connected since she was a child and the use of hearing aids. And the one thing that’s I guess good in today’s day is technology, there’s a lot of technology available for kids with hearing aids. She has a system at school where she can directly connect her hearing aids to a microphone her teacher wears. And so with all of the support she’s doing well without the support, she probably wouldn’t be, but she has immense support with her parents and school district.
Norcross: With her parents for sure. Kristy, with the FDA approval now in the books, what does it mean in terms of families getting access to this treatment?
Knight: Yes, it’s incredibly exciting and I’m so grateful that all of the work that’s been done to lead to the FDA approval. I think the next steps [are] to identify pediatric oncologists [who] would do this work, identify what children are eligible for the medication and who it would benefit most. But that really allows the opportunity to provide an intervention that will either reduce the hearing loss that’s caused by cisplatin or slow its progression. So I just wanted to add that STS doesn’t restore hearing once damage has occurred but it reduces the extent of damage that occurs and slows the progression of hearing during therapy.
Norcross: And how do you think this drug and these findings will impact pediatric cancer care in the future?
Knight: It’s potentially a huge change in clinical practice. I think over the decades cisplatin is such an effective drug and one of the unfortunate side effects is hearing loss and the thinking is that the hearing loss was an accepted and unfortunate consequence of achieving a cure for cancer. Having the opportunity to provide an intervention that protects hearing while allowing for effective treatment is just huge. It changes the lifetime quality of life for pediatric cancer survivors, if we can minimize or prevent hearing loss from occurring during therapy.
Norcross: Kristy Knight, Jennifer Boesche, thank you so much.
Knight: Thank you so much.
Boesche: Thank you.
Norcross: Kristy Knight is an audiologist at OHSU Doernbecher Children’s Hospital. Jennifer Boesche is the mother of a pediatric cancer patient there. She was also part of the effort to get the drug approved by the FDA.
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