This is the first prospective trial of scalp cooling with a highly controlled assessment of both efficacy and toxicity that has ever been done.
—Hope Rugo, MD
Hair loss remains one of the most dreaded side effects of chemotherapy, particularly for women. Scalp cooling caps worn by patients during chemotherapy infusion and for brief periods of time before and after offer these patients an option to preserve 50% or more of the hair on their heads. Although not new, the technology has improved, along with its tolerance and efficacy. Accordingly, scalp cooling caps have been in the news lately, including in The New York Times and National Public Radio.1,2
Expect more news shortly. A pivotal study evaluating the effectiveness of the DigniCap Scalp Cooling System among 100 women receiving chemotherapy for early-stage breast cancer has been submitted to the U.S. Food and Drug Administration (FDA) for approval, and study data will also be presented at this year’s ASCO Annual Meeting, May 29 to June 2, in Chicago.
“This is the first prospective trial of scalp cooling with a highly controlled assessment of both efficacy and toxicity that has ever been done,” Hope Rugo, MD, told The ASCO Post. Dr. Rugo is Director, Breast Oncology and Clinical Trials Education, and Professor of Medicine at the University of California, San Francisco (UCSF), one of the five trial sites.
Eligible patients included those with stage I or II breast cancer who were scheduled to start adjuvant chemotherapy. Hair was evaluated with photographs at baseline and before each cycle of chemotherapy, then graded by the patients themselves using a validated scale. The primary endpoint was the grade of hair loss 1 month after completing adjuvant chemotherapy. As explained by Dr. Rugo, success was defined as “less than 50% of hair being lost, and the majority of patients reached that endpoint.” Follow-up continues at 3 and 6 months and then long term to assess disease status.
“We have met our endpoints as we set forth. Scalp cooling with the Dignicap system seems to be very tolerable and can be easily incorporated into the infusion setting. So we are hopeful that this will all come to fruition,” Dr. Rugo stated.
Used in Other Settings
The DigniCap scalp cooling system consists of a cooling and control unit that pumps liquid coolant through a silicone inner cap with maze-like circuits and an outer insulating cap. According to the website of Dignitana, the Swedish manufacturer of the DigniCap, the system is approved for marketing in most European countries, Canada, China, and elsewhere.3
Although the current study involved only patients with breast cancer, patients in other countries receiving chemotherapy for other solid tumors have also used DigniCap. “There are many places in the world where it has been used for different cancers,” Dr. Rugo said. “It can be used in both the early- and late-stage setting. We are obviously studying it in the early-stage setting, but patients around the world have used it in the metastatic setting as well,” including patients with ovarian and other cancers treated with adjuvant chemotherapy associated with hair loss.
Separate Registry Study
The DigniCap is not the only scalp cooling method, nor even the only method being tested at the UCSF. A separate registry study has been set up there to follow patients using Penguin Cold Caps.
These caps do not attach to a cooling unit but must be kept in a freezer or on dry ice until just before use. A crylon gel inside the cap remains pliable when cooled and allows the cap to be fitted onto different sized and shaped heads. Velcro fasteners hold the caps in place. The caps must be changed every 30 minutes, so multiple caps are needed for patients to keep their scalps cool for the period before, during, and after chemotherapy.
For the registry study, physicians treating patients using the Penguin Cold Caps complete a form indicating the amount of hair loss. The study, however, does not include “taking multiple photographs and comparing them all to baseline and doing a rigorous approach like we did with the DigniCap,” Dr. Rugo noted.
“We will be presenting some of our updated registry data at an upcoming meeting as well,” she added. Although there have been some small studies conducted using the Penguin Cold Cap, “our registry study will be among the biggest databases using the Penguin Cold Cap,” Dr. Rugo said.
According to the Penguin website, because cold cap therapy has not yet been approved by the FDA, “we are therefore not allowed to sell our caps, but we are however allowed to rent them to chemotherapy patients who choose to use them at their own risk.”4
A third cooling system, known as the Paxman Scalp Cooling System, is more akin to the DigniCap and consists of a silicone cap connected to a small compact refrigeration unit. According to the website of Paxman Coolers Limited, based in the United Kingdom, the “Paxman Scalp Cooling System is under clinical investigation in the United States” but “has not been approved by the FDA and is not currently available for sale in the United States.”5
Gradual vs Immediate Cooling
The New York Times article noted that the DigniCap is “less labor intensive” than the Penguin Cold Cap, and Dr. Rugo generally agreed with that assessment.
“With the DigniCap, you just sit down and put it on,” she said. “It has to be fitted properly to your head to make sure there aren’t a lot of air pockets, and that takes a little while. Proper fitting is important. The company is continuing to work on improving the fit over time.”
The circulating coolant inside the cap gets colder gradually. “Some people have noted that that the initial cooling is harder and is sometimes associated with a mild headache, but then they adjust with resolution of the symptom as the cap remains cold. They get used to it,” Dr. Rugo said.
“When you put the Penguin Cold Cap on, it is cold right away. In the initial part of the cooling process, some people develop mild nausea or a headache.”
The Penguin Cold Cap “is more difficult to use” than the DigniCap, Dr. Rugo said, because the caps have to be kept in a freezer until right before they are ready to be used, and then to ensure that the scalp is kept cold enough, the caps have be to changed every 30 minutes. This means that the facility where the patient is receiving chemotherapy has to have freezers readily available to patients using Penguin Cold Caps. The caps are stored in a refrigerator between uses. In addition, the patient must have a helper present for the duration of treatment who fits and changes the caps. In some areas of the country, paid helpers are available.
“We have freezers purchased with philanthropic funding, but most sites don’t,” Dr. Rugo said. “A site would need to buy freezers if it has a lot of patients using the Penguin caps; otherwise, the patient must bring the caps to the infusion center using coolers and dry ice to keep the caps cold for the duration of treatment, then store them at home.
Generally Well Tolerated
Although scalp cooling has generally been well tolerated, “there are always some patients who drop out because they don’t like the cold, or because they have more hair loss than expected,” Dr. Rugo said.
“For DigniCap, we had very few people drop out of the main study. At all the sites, there was at least one person who dropped out, but mostly people dropped out because they thought they were losing too much hair and maybe an occasional few because they were cold. Even if you have most of the patients keep most of their hair, there will be some people who don’t like the amount of hair loss.”
The remaining hair may be more brittle and fragile, and because of this, patients are advised to treat it tenderly; use only gentle natural hair care products; and avoid daily shampooing, blow-drying, and perming or coloring. This impacts women differently: “I had one woman tell me she would rather lose her hair than not dye it, but for most women it is far preferable to keep most of their hair,” Dr. Rugo said.
Most individuals “are really happy to have” the option of scalp cooling, “because when you are done with chemotherapy, you can dye your hair,” Dr. Rugo said. “Even if you lose 50% of your hair, you are going to have a full head of hair that you feel comfortable with much faster, because it all starts filling in. But if you have no hair at all, it can take a long time.”
Stronger and Longer Chemotherapy
“The stronger the chemo and the longer the duration, the harder it is to keep your hair,” Dr. Rugo noted. Even when using the cold cap, “you have to be very careful and not worry about some of your hair falling out,” she added.
“We have people using Penguin Cold Caps with standard intensive anthracycline/taxane sequential therapy, and they generally lose some hair during their chemotherapy,” she said. “With ACT [doxorubicin, cyclophosphamide followed by paclitaxel], it is just harder to keep your hair. But some people have done it, particularly with the weekly paclitaxel schedule either before or after AC, and they can end up with more than 50% of their hair,” Dr. Rugo said.
The Penguin website cites a study concluding that Penguin Cold Caps were effective for protection from hair loss caused by taxanes, anthracyclines, and etoposide.6 Dr. Rugo noted that “outside of our standard chemotherapy regimens, we haven’t done a lot of testing in terms of variations in efficacy between different people or different types of regimens.”
Low Risk of Scalp Metastases
Coexisting with cold caps are concerns about cold cap users being at risk for scalp metastasis, because the cap may constrict blood vessels and limit the amount of chemotherapy penetrating the scalp. “That was what we understood about cold caps 30 years ago, when I was training, that they could increase the risk of scalp metastases because you didn’t get the chemotherapy to the scalp, and that would be a risk for patients you wouldn’t want to take,” Dr. Rugo reflected.
“We understand a lot more about the biology of cancer and metastatic disease now; it turns out that the risk of metastases to the scalp is extremely low, and as a first event for advanced disease, it is even lower. Mostly, scalp metatases are seen after people have already had metastases to other places in the body, and in total, only about 1.2% of all metastases are found in the scalp,” Dr. Rugo continued.
Scalp metastasis “would have to be the first site of metastatic disease to postulate that is has anything to do with scalp cooling, and that is very uncommon in the studies that are available. I’ve reviewed over 4,000 patients reported in clinical trials,7 and it is just exceedingly rare and doesn’t seem to be any higher in risk, from what we can tell, in patients who are using the cold cap.” ■
Disclosure: Dr. Rugo reported no potential conflicts of interest.
1. Parker-Pope T: Keeping your hair in chemo. The New York Times, March 9, 2015. Available at well.blogs.nytimes.com/2015/03/09/keeping-your-hair-in-chemo/. Accessed April 7, 2015.
2. Patients freeze scalps to save hair during chemo. National Public Radio, March 22, 2105. Available at nhpr.org/post/patients-freeze-scalps-save-hair-during-chemo. Accessed April 7, 2015.
3. Dignitana AB: Dignitana AB collaborates with Target Health Inc. to conduct pivotal study using proprietary clinical trial software. Available at www.dignitana.se. Accessed March 19, 2015.
4. Penguin Cold Caps: Reducing chemotherapy induced hair low: Frequently asked questions. Available at penguincoldcaps.com. Accessed March 19, 2105.
5. Paxman Coolers Limited: Paxman embracing life: patients. Available at http://www.paxman-coolers.co.uk. Accessed March 24, 2015.
6. Katsimbri P, Bamias A, Pavlidis N: Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. Eur J Cancer 36:766-771, 2000.
7. Rugo H, Melisko M: Efficacy and safety of scalp cooling to prevent chemotherapy (CTX) induced alopecia: A review of available data. 2011 International Conference of Early Breast Cancer. Abstract P331.
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