Portal de Periódicos da CAPES

FDA Clearance Puts Scalp Cooling Devices In Treatment Toolbox

2017; Wolters Kluwer; Volume: 39; Issue: 14 Linguagem: Inglês

10.1097/01.cot.0000521877.38051.c9

1548-4688

Valerie Neff Newitt,

Economic and Financial Impacts of Cancer

scalp cooling devices; chemotherapy: scalp cooling devices; chemotherapyWhen patient Patricia Popielic of Victor, N.Y., was diagnosed with breast cancer 2 years ago and learned she needed chemotherapy, her immediate thought was, “... Oh my God, I am going to lose my hair. That was the biggest fear for me,” said Popielic, who had already grappled with the deeper issues of having cancer. “Hair is part of my identity.” Popielic's reaction was not uncommon. While the aesthetics of hair is usually left to stylists, it moves into the medical realm when hair loss takes aim at the vulnerability of cancer patients. When chemotherapy results in alopecia, as it often does, patients perceive losses of control, emotional fortitude, and a weakening quality of life. Further, it has been reported in literature that some 8 percent of patients refuse chemotherapy simply to avoid losing their hair. It's a decision that, in a worst-case scenario, could result in the greatest loss of all—life. It was no small matter, then, when in April the FDA cleared a new British scalp cooler that helps reduce hair loss among breast cancer patients. This device is the second to be cleared for marketing in the U.S. Because cold constricts blood vessels in the scalp, it prohibits damage to hair follicles and minimizes hair loss for some patients. The cleared cooling systems work best with specific drug regimens, but not with all. First out of the FDA gate was the DigniCap from Dignitana, cleared in 2015. William Cronin, CEO of Dignitana Inc., first became involved with scalp cooling when his wife Lizzy was diagnosed with breast cancer 9 years ago. “Nothing prepares you for those words ‘you have cancer,’” he reflected earnestly. “Lizzy was able to use a manual scalp cooling device, which made it possible for her to keep her hair through six rounds of chemo. It made such a difference in her sense of well-being. When I heard about the DigniCap system shortly after our family's experience, I made it my life's mission to bring this advanced technology to as many patients as possible.” In early July, the FDA had just expanded that clearance to include other solid tumors such as prostate, lung, and gynecological cancers and many other forms of the disease. Patients Make the Case “Fear of losing hair varies among diverse populations,” noted oncologist Marcia Krebs, MD, Popielic's doctor at the Wilmot Cancer Institute, University of Rochester Medical Center in New York. “Explaining the probability of hair loss is a very difficult conversation to have with Indian and Hispanic women, for example; their long, dark hair is an important part of their culture and their personal identity.” Krebs also noted the stage of a patient's disease may influence patients' decisions in accepting drugs that drive hair loss. “Patients starting adjuvant therapy—going for a cure—are more likely to deal with hair loss. They know it is temporary, and they simply want to get it done, get healthy, and get on with life,” she said. “My metastatic patients, however, are the ones who fit that 8 percent refusal statistic. They are dealing with the reality of a terminal illness, and they question, ‘Why should I go on medicines that will make me lose my hair and feel even worse than I do now?’ I have to challenge myself to get them to go through treatment. I may even have to pick a regimen that will not make them lose their hair.” Popielic said the prospect of losing her hair was partially a privacy issue. “I didn't want to tell everyone what I was going through; but I knew if I was bald, everyone would know,” she said. So she opted to try an earlier version of a cooling cap (distinct from a “device”), which was both a bit cumbersome in use and expensive. “I didn't have time to shop around; I needed to make a decision before I started therapy.” She settled on a company from whom she rented equipment that was sent to her infusion center, including a series of gel caps she had to keep packed in dry ice during infusion. She placed the caps on her scalp, and as one lost its cooling capacity, she swapped it out for another. The caps were used pre-, mid-, and post-infusion. Popielic said it cost between $500-$600 for rental equipment, caps, and dry ice at each of six infusion sessions—approximately $3,000-$3,600 in total for scalp cooling, none of which was covered by insurance. But she personally felt it worth every penny. “It wasn't cheap,” she admitted, “but I kept most of my hair. It did thin, and I had to change my style a bit. But I never once had to wear the wig I had bought just in case. It's still in the box. Today, my hair has come back thick, shiny, and healthy looking.” Studies Ease Concern Popielic believes all cancer patients should be informed about cooling caps. But until the recent FDA clearance, there wasn't much interest from providers. Krebs explained the reticence. “Chemotherapy is intended to go through the bloodstream and reach every part and organ of the body. So if the cold caps reduce blood flow to the scalp, are we putting patients at risk of having a recurrence or metastasis in the scalp due to reducing the blood flow there? For a long time, that has been a nagging doubt in providers' minds.” However, clinical trials preceding the FDA device clearances have given providers and their patients reason to breathe easier. “Dignitana has been working with major academic medical centers to bring clinically tested scalp cooling to the U.S. for almost a decade,” said Cronin. The effort started at the University of California San Francisco when a patient of oncologist Hope S. Rugo, MD, Director of Breast Oncology and Clinical Trials Education at UC San Francisco and a breast cancer specialist with the UCSF Helen Diller Family Comprehensive Cancer Center, inquired about the possibility of using scalp cooling treatments as she underwent chemotherapy. “Hair loss associated with chemotherapy can be devastating for many women,” said Rugo, who later spearheaded Dignitana's clinical trials. As the system was tested and perfected, word spread of its successes in hair retention. “By the time we received clearance from the FDA in December 2015, women and physicians had already started sharing their stories in the media and medical centers were eager to speak with us and learn more,” said Cronin. “With breast cancer patients, we have seen positive results with scalp cooling treatments, although success is dependent on the type and dose of chemotherapy. Patients with other cancers—including gynecologic cancers and cancer of the prostate—using similar chemotherapy treatments may also benefit from scalp cooling to preserve their hair,” Rugo explained. “We are pleased that the FDA has expanded clearance so that scalp cooling can be used by both women and men who have other types of solid tumors.” Julie Nangia, MD, Assistant Professor in the Lester and Sue Smith Breast Center within the NCI-designated Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine, Houston, led a randomized trial while utilizing the Paxman Cooling System (JAMA 2017;317(6):596-605). Nangia's interest in studying cooling systems arose from a colleague's frustration in being unable to offer any FDA-approved scalp cooling system for a patient. When her colleague asked if she would be interested in working on a trial, she immediately took up the cause. “It took me about 3 years to get the FDA to agree to do the trial,” Nangia explained. “It might not have happened had it not been for safety data that came out of Europe counteracting concern about scalp metastases.” The experience and studies from other countries showed that there was no evidence of increased rates of metastases or changes in rates of survival in patients using scalp cooling devices. “That is when the FDA allowed trials to begin,” Nangia recounted. “Ours was the only randomized trial in the world. We had a control group; two-thirds of the patients had scalp cooling and one-third did not. We designed the trial this way to find out the exact rates of hair retention with the chemotherapies.” The trial ended early because the superiority analysis proved the device to be very effective. “At interim analysis, 50 percent of women who used cooling caps kept their hair, versus 0 percent of women in the control group,” said Nangia. “That's pretty good overall. But then there are certain types of chemotherapies for which the device is more effective—taxanes and anthracyclines, two of the most common for treating breast cancer. Devices prevent hair loss best in the taxane group, but are still effective in both groups.” What Is a ‘Cooling System’? Richard Paxman, CEO of Paxman Coolers Ltd., in Great Britain, explained that the Paxman Cooling System “... is actually a refrigeration cooling system. We pump a proprietary liquid coolant—a bit like antifreeze—at a specific temperature around a silicone cooling cap. It is controlled so that we can maintain the patient scalp at a certain level of temperature throughout the treatment. The problem with older cooling caps was they didn't have the controls, so patients would have a large number of gel cold caps in dry ice and change those every 20 minutes. This means there would be a variation in temperature as a cap started to lose its coldness, and that variation created poor results. Also, it was nearly impossible to keep gel caps uniformly on the head.” The new device is a leap in technology born of a personal loss. “Back in the '90s my mum, only 34, was diagnosed with late stage breast cancer. One of her biggest fears was that she was going to lose her hair through the treatment. At that time, they were using the older scalp cooling method and she decided to give it a go. But unfortunately for my mum, it didn't work,” Paxman lamented. “Today we are aware there are lots of variable factors, but back then we didn't know whether the culprit was the technology, the drug regimen, or both.” Paxman's father had never worked in the medical space. “Our family background was in refrigeration—about 50 years' experience in cooling beer,” Paxman said. “It was quite a leap when my dad was determined to understand why cooling caps didn't work for my mum, and what we could do to make sure this would be more efficacious in the future for other patients. Having learned that cold protects hair follicles, we decided to apply our knowledge in making a refrigeration-controlled cooling device that could create better results and a better patient experience.” The effort has proven a phenomenal success for the Paxman family business. “Over 90 percent of all of our hospitals in the U.K. are using our equipment. And there are 2,500 systems in use around the world. It makes me incredibly proud,” said Paxman. “It's my mum's legacy. Without what she went through, patients would not be benefitting from this product now.” With the FDA clearance achieved, Paxman said the company expects to have 250 systems in place in the U.S. this year. “U.S. physician support has been tremendous so far,” he added. “Providers and hospital administrators see this as a patient benefit they can offer—a way to drive better patient outcomes through better quality of life.” In addition to offering an improved cap and refrigeration, the Paxman model also offers caps used only by single patients, reducing the need for lengthy disinfectants between patients, as well as billing options that take the burden off of hospitals, should they opt to take advantage of that possibility. The technology is not dissimilar to that of DigniCap, its forerunner in the U.S. market. The DigniCap Scalp Cooling System features a tight-fitting silicone cooling cap placed directly on the head, and an outer neoprene cap that insulates and secures the silicone cap. According to information provided by the company, “The cooling cap is connected to a cooling and control unit. A liquid coolant circulates throughout the silicone cap, delivering consistent and controlled cooling to all areas of the scalp. Once the cap is fitted to the head, the temperature of the scalp is lowered to be just above freezing temperature, resulting in vasoconstriction with reduced delivery of chemotherapy to the scalp, as well as reduced cellular uptake of drugs due to decreased intra-follicular metabolic rate. These factors together minimize the hair loss that is a side effect of many chemotherapy agents.” To date, DigniCap is available at more than 80 clinical sites across 21 states in the U.S. Cronin further explained, “The DigniCap System has three patented sensors for improved performance and comfort, and is designed to keep scalp temperature at proper levels throughout the infusion process. We've also put a great deal of effort into making the machine itself easy to use and adapt for infusion room clinicians and technicians. Every medical center is different, and in the 18 months, we've worked with a wide range of medical centers across the country, from Mount Sinai Health Systems in New York and the UCSF Helen Diller Family Cancer Center in San Francisco, to smaller practices like Chesapeake Oncology and Hematology Associates in the Baltimore area and Norton Cancer Center in Louisville, Ky., to develop customized protocols that interface efficiently with each center's individual workflow.” Going Forward Findings by those investigative teams who have studied and reported on cooling systems have the potential to inform care plans. “I think this can drive some important decision-making,” Nangia said. “For example, for HER2-positive cancers there are two common regimens—one contains anthracyclines and one does not. Now we realize these devices are most effective in non-anthracycline regimens. So, if keeping hair is extremely important to a patient and there is an equally effective option that increases hair retention rates, maybe that regimen is better for that patient. Consider, too, a patient getting a taxane. We now know almost everyone using the device keeps their hair when getting weekly Taxol, but experiences more hair loss with an every-three-weeks regimen of docetaxel. So now we can weigh similar drugs, with equal efficacy.” Nangia said oncologists must raise their awareness about the regimens that are more effective with cooling devices to be able to better guide patients. Toward this end, she presented a poster (http://meetinglibrary.asco.org/record/152291/poster) at ASCO 2017 that detailed specific regimens and hair retention rates. Pamela Crilley, DO, Chair, Department of Medical Oncology at Cancer Treatment Centers of America (CTCA), and medical oncologist at CTCA at Eastern Regional Medical Center in Philadelphia, is representative of many voices in the oncology community who believe adoption of FDA-approved cooling systems will be swift. “That big question about the possibility of scalp metastases when using cooling devices appears to have been answered,” said Crilley. “And while cost and reimbursement will be an issue for the patients, recent studies may help them to circumvent the expense. Quality of life is an issue that must be taken into account; providers and insurers are interested in improving quality of life for cancer patients.” Some help in the cost to patients may be available from non-profit organizations, such as HairToStay (www.hairtostay.org), which offers subsidies for scalp cooling to patients who cannot afford it. While Crilley has not yet used the cooling devices in practice, she said, “I'm excited to do so. Patients have asked about them in the past. Now that we have clinical trials supportive of them, I believe they will be a great and welcomed addition to patient care.” Nangia cautioned providers to keep a realistic perspective in mind, and educate patients around the cooling systems' true capabilities. “I had to create a patient expectations handout for the trial to show what to expect,” she said, explaining that some patients thought they would lose no hair at all. But the reality is most patients, even with the device, experienced hair thinning of up to 30 percent of their hair, “... but not so much that it is visibly obvious. “What I would tell oncologists is that I do think the devices are safe, and they do work,” Nangia continued. “But they are not 100 percent effective; they are 50 percent effective. And they are more effective with certain types of chemotherapy. While there is a reality patients will have hair thinning, if they can keep at least half of their hair and not have to wear a wig, I would consider that a success. And most patients would, too.” Dignitana offered a slightly higher rate of hair retention. According to Cronin, “As reported in JAMA earlier this year, 66.3 percent of patients with early-stage breast cancer using the DigniCap Scalp Cooling System in multi-center clinical trials kept at least 50 percent of their hair (2017;317(6):606-614). Five percent of patients who wore the cap reported no hair loss at all, and 36 percent lost 25 percent or less of their hair by the end of their adjuvant chemotherapy. The women who did not receive scalp-cooling treatment lost most or all of their hair.” Cronin noted that bringing cooling caps to a mass market with FDA clearance “... has been an exciting process both from a business perspective and personally. To be able to help someone avoid losing their hair as they navigate the challenges of a cancer diagnosis has been rewarding beyond all expectation.” Valerie Neff Newitt is a contributing writer.