(252 days)
The Paxman Scalp Cooler is indicated to reduce the likelihood of chemotherapy-induced alopecia (CIA) in cancer patients with solid tumors.
The Paxman Scalp Cooler is a self-contained, mobile, electrically-powered refrigeration unit that circulates a refrigerated liquid coolant, at a pre-set temperature and flow rate, through a cooling cap, which is fitted to the top of the patient's head and connected to the refrigeration unit by a pair of coolant lines. A touchscreen controller with a menu-driven, graphical user interface, integrated into the refrigeration unit, allows the healthcare professional to initiate, monitor, and complete the scalp cooling process.
The provided text is a 510(k) summary for the Paxman Scalp Cooler, which is a medical device intended to reduce chemotherapy-induced alopecia. The document outlines the device's characteristics, indications for use, and a comparison to a predicate device. It also summarizes clinical performance data.
However, the document does not contain the specific information typically associated with acceptance criteria and a study proving a new device meets these criteria in the context of an Artificial Intelligence/Machine Learning (AI/ML) device. Instead, this 510(k) is for an expansion of the indication for use of an already cleared device, stating that "No additional testing was conducted for this 510(k) to support substantial equivalence." The supporting clinical data provided are summaries of existing published and non-published studies, primarily focusing on the device's performance in different patient populations and with various chemotherapy regimens.
Therefore, I cannot extract information related to acceptance criteria, sample sizes for a test set, expert involvement, adjudication methods, MRMC studies, standalone performance, ground truth establishment for novel AI/ML device validation.
The closest I can get to "acceptance criteria" based on the provided text would be the success rates observed in the clinical studies, which demonstrate whether the device performed as intended in reducing alopecia.
Here's an attempt to organize the available relevant information from the document, with caveats where the requested information is not present:
Study Proving Device Meets Acceptance Criteria (as interpreted from a 510(k) for an expanded indication)
The Paxman Scalp Cooler's expanded indication for use (from "women with breast cancer" to "cancer patients with solid tumors") was supported by a review of published and non-published clinical data from the Paxman Scalp Cooling System. This was not a new clinical study specifically designed to establish performance for the expanded indication, but rather a compilation of existing evidence. The previous 510(k) (K163484) for the device's initial clearance would have included performance testing, but the details are not fully provided here, beyond a general statement that "All tests met the pre-determined specifications and acceptance criteria and demonstrated the Paxman Scalp Cooler to be safe and effective as labeled."
1. Table of Acceptance Criteria (Interpreted from Clinical Outcomes) and Reported Device Performance
Since this is a 510(k) for an expanded indication and not a new clinical trial with pre-defined acceptance criteria for a novel device, I will present the success rates and observations from the most relevant studies for showing the device's effectiveness in reducing chemotherapy-induced alopecia for solid tumors. The "acceptance criteria" here are implied by the positive outcomes and conclusions drawn in the existing literature.
| Metric (Implied Acceptance Criteria) | Reported Device Performance (from various studies) | Supporting Study |
|---|---|---|
| Reduction in chemotherapy-induced alopecia (CIA) / Successful hair preservation | - Overall, 50% of 1411 patients did not wear a head cover during their last chemotherapy session. - Success rates varied from 8% (TAC chemotherapy) to 95% (paclitaxel treatment). - For the SCALP study (K163484 predicate), 53.1% (95% CI, 44.5%-61.4%) had successful hair preservation in the cooling group vs. 0% in control group (95% CI, 0%-6.6%). - Alopecia occurrence with 3-weekly docetaxel: Paxman: 23% vs. No cooling: 74%. - Alopecia occurrence with weekly docetaxel: Paxman: 7% vs. No cooling: 17%. - 69.7% of patients completed sensor-controlled scalp cooling, with 58.6% experiencing complete hair preservation (DS 0) and 11.1% partial success (DS 1-2). - 91.21% overall scalp cooling had excellent results in the Lebanese study, with 6/6 (100%) patients on TAC showing no signs of hair loss. | - Dutch Scalp Cooling Registry (2012, 2017) - Paxman Coolers Limited SCALP study (Nangia J, et al. 2017) - Betticher DC, et al. (2013) (Paxman Swiss Clinical Studies of Efficacy) - Kurbacher CM, et al. (2017) - Paxman Lebanese Clinical Studies of Efficacy |
| Patient Tolerability and Comfort | - "Well-tolerated and were infrequently discontinued by patients." - "The sensation of cold was sometimes reported, no serious adverse events occurred, and patient ratings of cooling therapy were generally favorable." - SCALP study: 71 device-related adverse events, all grades 1 and 2. No serious device-related adverse events. - 85% of patients (Massey C, 2004) described it as very comfortable, reasonably comfortable or comfortable. - 73.3% of patients (El-saka RO, et al., 2009) were comfortable during cooling. - 5% of patients (Betticher DC, et al., 2013) reported adverse events (most frequently sensation of cold). - 5% of patients (Paxman UK Clinical Study of Efficacy) discontinued scalp cooling. - 5% of patients (Paxman Netherlands Clinical Study of Efficacy/2) discontinued due to intolerance. | - General conclusion from clinical literature - Nangia J, et al. (2017) - Massey C (2004) - El-saka RO, et al. (2009) - Betticher DC, et al. (2013) - Paxman UK Clinical Study of Efficacy - Paxman Netherlands Clinical Study of Efficacy/2 |
| No significant long-term adverse effects (e.g., increased scalp metastasis) | - "No unfavorable development of disease due to scalp cooling has been documented in patients with solid tumors." - "No difference in overall mortality was observed between scalp-cooled patients and non-scalp-cooled patients." - Scalp cooling had "no negative effect on survival." | - van den Hurk, CJ, et al. (2013) - Lemieux J, et al. (2015) |
2. Sample sizes for the test set and data provenance:
- Test Set Sample Sizes:
- Dutch Scalp Cooling Registry: Over 6000 cancer patients enrolled (since 2006, up to 2017 data points provided in tables). Specific patient counts provided for different years (e.g., n=1411 for 2006-2010, n=4864 for 2010-2015, n=827 for 2015-2017).
- Paxman Coolers Limited SCALP study (NCT01986140): 182 women with stage 1 or II breast cancer (119 in cooling group, 63 in no cooling group). The publication reports on an interim analysis of n=142 patients (95 in cooling, 47 in control).
- Massey C (2004): 94 breast cancer patients.
- Bini M, et al. (2004): 47 breast cancer patients.
- Betticher DC, et al. (2013): 238 patients with solid tumors (128 Paxman, 77 cool cap, 39 no cooling).
- Kurbacher CM, et al. (2017): 99 female patients.
- Silva G, et al. (2016): 20 female patients.
- Paxman Lebanese Clinical Studies of Efficacy: 91 cancer patients.
- Data Provenance: The studies summarized are from various international locations including the Netherlands (Dutch Registry, Paxman Netherlands studies), UK (Massey C, Paxman UK study), Switzerland (Betticher DC, Paxman Swiss studies), Brazil (Silva G), Lebanon (Paxman Lebanese study), and the US (Nangia J, et al. - SCALP study).
- Retrospective or Prospective:
- Dutch Scalp Cooling Registry: Retrospective (registry data collection).
- Paxman Coolers Limited SCALP study (Nangia J, et al.): Randomized, multi-center, prospective clinical trial.
- Lemieux J, et al. (2015): Retrospective cohort study.
- Massey C (2004): Open, non-randomized, observational, multi-center.
- Bini M, et al. (2004): Observational, single-center.
- Falanga M, et al. (2010): Observational, single-center (pilot study).
- El-saka RO, et al. (2009): Randomized.
- Betticher DC, et al. (2013): Open-label, prospective, non-randomized.
- Kurbacher CM, et al. (2017): Retrospective analysis.
- Silva G, et al. (2016): Observational.
- Boyle F, et al. (2015): Focus group/semi-structured interview (qualitative).
- Kinoshita T, et al. (2015): Case review.
- Letchford DB, et al. (2016): Ongoing prospective cohort.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided as the summarized studies are clinical trials and observational studies, not typically "ground truth" establishment for an AI/ML algorithm's test set. Hair loss assessment was done by clinicians, nurses, or through patient self-reporting, often using standardized scales (WHO grading system, CTCAE v4.0).
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
This information is not applicable as it's not a reader study for an AI/ML algorithm's test set. Hair loss assessment methods varied by study (e.g., blinded clinician, patient's clinician, patient self-reporting).
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
This information is not applicable. The studies describe the effectiveness of the device (scalp cooler) itself, not the assistance of an AI to human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
This information is not applicable. The device is a physical cooling system, not a software algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The "ground truth" for the effectiveness of the device in these studies was primarily clinical outcomes data related to hair preservation (e.g., success defined as not needing a wig/head cover, or specified grades of alopecia using scales like WHO grading system and CTCAE). Safety data involved reporting of adverse events. Survivability data were also used in some studies.
8. The sample size for the training set:
This information is not applicable as the device is a physical medical device, not an AI/ML algorithm that requires a "training set."
9. How the ground truth for the training set was established:
This information is not applicable for the same reason as above.
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Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA). The HHS logo is on the left, and the FDA logo is on the right. The FDA logo includes the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
June 7, 2018
Paxman Coolers Limited % Heather Crawford Senior Consultant, Quality and Regulatory Emergo Global Consulting, LLC 2500 Bee Cave Road Building 1, Suite 300 Austin, Texas 78746
Re: K173032
Trade/Device Name: Paxman Scalp Cooler Regulation Number: 21 CFR 878.4360 Regulation Name: Scalp Cooling System Regulatory Class: Class II Product Code: PMC Dated: May 2, 2018 Received: May 7, 2018
Dear Heather Crawford:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
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801); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely, Jennifer R. Stevenson -For Binita S. Ashar, M.D., M.B.A., F.A.C.S. Director Division of Surgical Devices Office of Device Evaluation
Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K173032
Device Name Paxman Scalp Cooler
Indications for Use (Describe)
The Paxman Scalp Cooler is indicated to reduce the likelihood of chemotherapy-induced alopecia (CIA) in cancer patients with solid tumors.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary
Paxman Scalp Cooler
K173032
1. Submission Sponsor
Paxman Coolers Limited
International House
Penistone Road
Fenay Bridge
Huddersfield
HD8 OLE
United Kingdom
Contact: Richard PAXMAN
Title: Managing Director
2. Submission Correspondent
Emergo Global Consulting, LLC
2500 Bee Cave Road
Building 1, Suite 300
Austin, TX 78746
Office Phone: (512) 327.9997
Contact: Heather Crawford, Senior Consultant, Quality and Regulatory
Email: project.management@emergogroup.com
3. Date Prepared
June 03, 2018
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4. Device Identification
| Trade/Proprietary Name: | Paxman Scalp Cooler |
|---|---|
| Common/Usual Name: | Scalp Cooling System |
| Classification Name: | Scalp Cooling System to Reduce the Likelihood of Chemotherapy-Induced Alopecia |
| Regulation Number: | 878.4360 |
| Product Code: | PMC, Scalp Cooling System |
| Device Class: | Class II |
| Classification Panel: | General and Plastic Surgery |
5. Legally Marketed Predicate/Reference Devices
Predicate Device: K163484, Paxman Scalp Cooler, Paxman Coolers Limited Reference Device: K170871, DigniCap Scalp Cooling System, Dignitana AB
6. Device Description
The Paxman Scalp Cooler is a scalp cooling system used to reduce the likelihood of chemotherapyinduced alopecia previously cleared by FDA in women with breast cancer (K163484). The only change from the previously cleared device is the indication for use from "women with breast cancer" to use in "cancer patients with solid tumors." There are no changes to the hardware or software in the subject device when compared to the device cleared under K163484.
The Paxman Scalp Cooler is a self-contained, mobile, electrically-powered refrigeration unit that circulates a refrigerated liquid coolant, at a pre-set temperature and flow rate, through a cooling cap, which is fitted to the top of the patient's head and connected to the refrigeration unit by a pair of coolant lines. A touchscreen controller with a menu-driven, graphical user interface, integrated into the refrigeration unit, allows the healthcare professional to initiate, monitor, and complete the scalp cooling process.
The touchscreen displays a menu-driven Graphical User Interface (GUI) that provides information to the user concerning the operational status of the scalp cooling unit; it also prompts the user to initiate some actions regarding the scalp cooling procedure and provides a timer count-down function for scalp cooling sessions. The GUI does not, however, directly control the scalp cooling process as there are pre-established programs for the scalp cooling administration.
The touchscreen controller provides feedback to the user concerning the status of the Paxman Scalp Cooler as it relates to the achievement of the pre-set temperature of the coolant, operation of the recirculation pump and connection of a cooling cap to the system. The software also
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provides a timer count-down function for the initiated pre- and post-infusion cooling procedure. At the end of the pre-set time, a message is displayed on the touchscreen, and a buzzer sounds to alert the user to the fact that the scalp cooling time is complete.
7. Indication for Use Statement
The Paxman Scalp Cooler is indicated to reduce the likelihood of chemotherapy-induced alopecia (CIA) in cancer patients with solid tumors.
8. Limitations
The sale, distribution, and use of Paxman Scalp Cooler are restricted to prescription use in accordance with 21 CFR §801.109.
Limitations on device use are also achieved through the following contraindications, warnings and precautions included in the instructions for use.
9. Contraindications
Scalp cooling is contraindicated in pediatric patients.
Scalp cooling is contraindicated in patients with:
- . An existing history of scalp metastases or the presence of scalp metastasis is suspected.
- Cancers of the head and neck.
- CNS malignancies (either primary or metastatic).
- Cold sensitivity, cold agglutinin disease, cryoglobulinemia, cryofibrinogenemia, cold migraine, cold urticaria, and post-traumatic cold dystrophy.
- . Hematological malignancies (leukemia, non-Hodgkin and other generalized lymphomas) or hematological malignancies that are being treated for cure.
- Imminent bone marrow ablation chemotherapy.
- . Imminent skull irradiation.
- . Previously received, or scheduled to undergo skull irradiation.
- . Scalp metastases have rarely been reported in the literature, but caution regarding their development has been a limitation for the broad-scale application of scalp cooling during chemotherapy. Theoretically, tumor cells that have seeded in the scalp might not receive adequate chemotherapy during hypothermia, thus allowing them to grow at a later date.
- . Severe liver or renal disease from any etiology who may not be able to metabolize or clear the metabolites of the chemotherapeutic agent.
- . Skin cancers including melanoma, squamous cell carcinoma, and Merkel cell carcinoma.
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- Small cell carcinoma of the lung.
- . Solid tumors that have a high likelihood for metastasis in transit.
- Squamous cell carcinoma of the lung.
10. Warnings and Precautions
Scalp and/or cutaneous metastases have been reported in patients with non-small cell lung cancer, colon cancer, renal cell carcinoma, ovarian cancer, and bladder cancer. Patients with advanced forms of these tumors may be more likely to experience scalp metastases with the scalp cooling system.
It cannot be guaranteed that scalp cooling will prevent all patients undergoing chemotherapy from losing any or all of their hair. The success rate of scalp cooling in reducing chemotherapyinduced hair loss varies from patient and according to the chemotherapy regimen administered.
Long-term effects of scalp-cooling and scalp metastasis have not been thoroughly studied.
Use of scalp cooling in the palliative setting in patients with metastatic cancer may also increase the risk for scalp metastases.
Use of scalp cooling with Taxanes plus anthracyclines when used together or in sequence has not been shown to be successful in preventing chemotherapeutic drug induced alopecia. The Paxman Scalp Cooler should not be used in these patients.
The effectiveness of this device in patients who have received previous chemotherapy has not been evaluated.
Clinical studies have demonstrated variable success rates in patient reduction of chemotherapyinduced alopecia with scalp cooling since the outcome is dependent on multiple factors including chemotherapy regimen, dose, duration of drug infusion, chemotherapy drug metabolism, and concomitant comorbidities. Data have shown that women who experience hair loss despite using scalp cooling might have worse quality of life than women who did not have scalp cooling.
The Paxman Scalp Cooler should only be used by appropriately qualified healthcare professionals who have been trained in the operation of the device.
Do not allow any liquids to be placed on the scalp cooler or near the touch screen controller, including drips from the cooling caps.
Avoid use at ambient temperatures of over 30°C/86°F.
Do not touch the side ventilation grills whilst the device is in use.
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11. Substantial Equivalence Discussion
Aside from the change in the Indications for Use, the Paxman Scalp Cooler is identical in technological characteristics, design, and performance to the predicate.
The following table compares the Paxman Scalp Cooler to the predicate device with respect to indications for use, principles of operation, technological characteristics, and performance testing. The comparison of the devices provides more detailed information regarding the basis for the determination of substantial equivalence. The subject device does not raise any new issues of safety or effectiveness based on the similarities to the predicate device.
| Subject Device | Predicate Device | ||
|---|---|---|---|
| Manufacturer | Paxman Coolers Limited | Paxman Coolers Limited | Significant Differences |
| Trade Name | Paxman Scalp Cooler | Paxman Scalp Cooler | |
| 510(k) Number | K173032 | K163484 | Not applicable |
| Product Code | PMC | PMC | Same |
| Regulation Number | 878.4360 | 878.4360 | Same |
| Regulation Name | Scalp Cooling System | Scalp Cooling System | Same |
| Indications for Use | The Paxman Scalp Cooler is indicated to reduce the likelihood of chemotherapy-induced alopecia (CIA) in cancer patients with solid tumors. | The Paxman Scalp Cooler is indicated to reduce the likelihood of chemotherapy-induced alopecia (CIA) in women with breast cancer. | The subject device is identical in technological characteristics to the predicate device K163484 apart from the indications for use, which are being broadened from “in women with breast cancer” to “in cancer patients with solid tumors.” The subject device indications for use are identical to DigniCap, |
Table 5A – Comparison of Characteristics
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| Subject Device | Predicate Device | Significant Differences | |
|---|---|---|---|
| Manufacturer | Paxman Coolers Limited | Paxman Coolers Limited | |
| Trade Name | Paxman Scalp Cooler | Paxman Scalp Cooler | K170871. |
| Mechanism of Action | The unit is a compact, mobile refrigeration unit which circulates liquid coolant at low pressure through a special cooling cap on the patient's head. The circulation of the refrigerated coolant through the cap extracts heat from the patient's scalp maintaining temperature. | The unit is a compact, mobile refrigeration unit which circulates liquid coolant at low pressure through a special cooling cap on the patient's head. The circulation of the refrigerated coolant through the cap extracts heat from the patient's scalp maintaining temperature. | Same |
| Technology Overview | The unit is composed of the main unit that contains the refrigeration components, touch screen controller, and coolant tank. There are detachable coolant lines with covers, detachable cooling cap with covers, and proprietary coolant. | The unit is composed of the main unit that contains the refrigeration components, touch screen controller, and coolant tank. There are detachable coolant lines with covers, detachable cooling cap with covers, and proprietary coolant. | Same |
| Patient Population | Cancer patients with solid tumors | Women with Stage I - II breast cancer undergoing neoadjuvant or adjuvant chemotherapy. | Differs - The expanded patient population includes all cancer patients with solid tumors, which includes women with breast cancer. |
| Set Cooling Time | Yes | Yes | Same |
| Pre/Post Cooling Time | Yes | Yes | Same |
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| Subject Device | Predicate Device | Significant Differences | |
|---|---|---|---|
| Manufacturer | Paxman Coolers Limited | Paxman Coolers Limited | |
| Trade Name | Paxman Scalp Cooler | Paxman Scalp Cooler | |
| Material of Cooling Cap | Silicone; Primasil Sil 100 silicone from 20 – 80 Shore Duromater | Silicone; Primasil Sil 100 silicone from 20 - 80 Shore Duromater | Same |
| Size of Cooling Cap | Small, Medium, Large | Small, Medium, Large | Same |
| Number of Cooling Caps/Lines | 2 | 2 | Same |
| Quick Disconnect | Yes | Yes | Same |
| Coolant Temperature Range | -15°C to 5°C | -15°C to 5°C | Same |
| Refrigerant Type | OrbisC (organic salt based) | OrbisC (organic salt based) | Same |
| Coolant Refilling | Yes | Yes | Same |
| Sterile | No | No | Same |
| Single-Use | No | No | Same |
| Main Unit Dimensions | Height: 640 mmWidth: 320 mmDepth: 420 mm | Height: 640 mmWidth: 320 mmDepth: 420 mm | Same |
| Weight | 29.5 kg | 29.5 kg | Same |
| AC Powered | 100 – 120 V, 50/60 Hz | 100 – 120 V, 50/60 Hz | Same |
| Touch Screen Interface | Yes | Yes | Same |
| Software Controlled | Yes | Yes | Same |
| Complies with | Yes | Yes | Same |
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| Subject Device | Predicate Device | Significant Differences | |
|---|---|---|---|
| Manufacturer | Paxman Coolers Limited | Paxman Coolers Limited | |
| Trade Name | Paxman Scalp Cooler | Paxman Scalp Cooler | |
| ISO 10993-1 | |||
| ElectricalSafety TestingPassed | Yes | Yes | Same |
12. Non-Clinical Performance Data
No additional testing was conducted for this 510(k) to support substantial equivalence. The device in this submission is identical to the previously cleared device, as the purpose of this application was for the expansion of the treatment population only. Testing of the predicate device included biocompatibility, shelf-life, shipping and packaging, electromagnetic compatibility and electrical safety, software, and bench testing. All tests met the pre-determined specifications and acceptance criteria and demonstrated the Paxman Scalp Cooler to be safe and effective as labeled.
13. Clinical Performance Data
Published and non-published clinical data support use of the Paxman Scalp Cooling System in cancer patients with solid tumors. Clinical data in this application comprises registry data, a manufacturer-sponsored clinical study, clinical literature and non-published studies as described below.
Dutch Scalp Cooling Registry
The Dutch Scalp Cooling Registry has enrolled over 6000 cancer patients, including multiple cancer types and varies chemotherapy regimens. Seventy-one percent of all solid tumor patients wore no head cover at their last cooling session (p < 0.05) compared to 50% of all breast cancer patients at their last cooling session. Registry data demonstrate some subgroups, e.g. patients treated with certain chemotherapeutic agents, including AC, DAC and Irino mono, as well as patients with Asian or chemically-colored hair may be least likely to benefit from scalp cooling.
Paxman Coolers Limited SCALP study
The Paxman Coolers Limited SCALP (Scalp Cooling to Prevent Chemo-induced Hair Loss) clinical study (ClinicalTrials.gov identifier: NCT01986140) was initiated to evaluate the safety and efficacy of the Paxman Scalp Cooler, in support of its initial indication to reduce the likelihood of CIA in women with breast cancer (K163484).
Successful hair preservation was demonstrated in 69 of 130 women with cooling (53.1%; 95%CJ, 44.5%-61.4%) compared with 0 of 54 women in the no cooling (control) group (0%; 95%C), 0%-
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6.6%) (success rate difference, 53.1%; 95%Cl, 44.5%-61.7%). Seventy-one device-related adverse events were reported in the cooling group, all grades 1 and 2. No serious device-related adverse events occurred.
Primary and secondary study endpoints are complete. Enrolled subjects are currently in long-term follow-up for disease status and survival.
Clinical literature and non-published studies
The performance and/or safety of scalp cooling with the Paxman Scalp Cooler is reported in the clinical literature and non-published studies. These documents report the effects of scalp cooling on a range of cancer types, chemotherapeutic agents and regimens, and patient characteristics. Scalp cooling treatments appear well-tolerated and were infrequently discontinued by patients. The sensation of cold was sometimes reported, no serious adverse events occurred, and patient ratings of cooling therapy were generally favorable.
Findings from the clinical literature include:
- . No unfavorable development of disease due to scalp cooling has been documented in patients with solid tumors, scalp cooling can safely be offered to patients treated with alopeciainducing chemotherapy;
- . Among women with stage I to II breast cancer receiving chemotherapy with a taxane, anthracycline, or both, those who underwent scalp cooling were significantly more likely to have < 50% hair loss after the 4th chemotherapy cycle compared with those who received no scalp cooling; and
- Solid tumor cancer patients undergoing docetaxel chemotherapy with Paxman scalp cooling had a lower occurrence of alopecia compared to patients without cooling. Alopecia occurrence among Paxman Scalp Cooler patients in the 3-weekly docetaxel regimen group was 23% compared with 74% in no cooling (control) patients. Similarly, alopecia occurrence was 7% among Paxman Scalp Cooler patients undergoing weekly docetaxel treatments compared with 17% in the no cooling patient group.
Findings from non-published studies include:
- . An observational multi-center study of patients with several types of cancers reported a head cover was used by 51% of scalp-cooled patients; 38% of scalp-cooled patients were thought to have needlessly purchased a wig;
- A multi-center trial of breast, prostate and lung cancer patients demonstrated no head cover or wig was required in 88% of patients following 45 minutes of post-infusion cooling after 3weekly docetaxel, compared with 74% of patients after 90 minutes post-infusion cooling; and
- A multi-center observational study of Lebanese patients reported a 91% success rate including 6 of 6 (100%) patients undergoing treatment with TAC who showed no signs of hair loss.
Table 5B and Table 5C, respectively, summarize published and non-published studies using the Paxman Scalp Cooling System on patients receiving chemotherapy.
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14. Statement of Substantial Equivalence
The Paxman Scalp Cooler described in this application is unchanged from the device previously cleared in K163484. This application is limited to a revision of the indications for use. The clinical data from the Dutch Scalp Cooling Registry, Paxman Coolers Limited SCALP study, clinical literature and non-published studies provided in this application demonstrate the Paxman Scalp Cooler can be used to reduce the likelihood of chemotherapy-induced alopecia in cancer patients with solid tumors.
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| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
|---|---|---|---|---|---|---|---|
| van den Hurk, CJ,et al. (2012)Note: Study datais included 2006-2010 Dutchregistry data andPaxmanNetherlandsClinical Study ofEfficacy/3 | Registry,multi-center(28)Nurses andpatientscompletedquestionnaireson patients,chemotherapyand scalpcooling;logisticregressionanalysis wasused toexamineassociatedcharacteristicsof the scalpcooling result | n=1411Male n=50 (4%),female n=1357(96%), missing n=4Types of cancer:breast n=1216(86%), femalegenital n=65 (5%),gastrointestinal/colorectal n=63(4%), lung n=19(1%), prostate n=27(2%), other n=16(1%), missing n=5 | A60C600 (AC) (n=74),A60C600/D100 (ACD)(n=16), ACT overall(n=50), D75A50C500(TAC) (n=66), D overall(n=120), F500A50C500(FAC) (n=39), FECoverall (n=752),F500E100C500/D100(FE100CD) (n=46),TCarbo overall (n=68),T70-90 (42), Irino 250(n=42), other (n=64) | To estimate the results ofscalp cooling for currentlyused chemotherapies toprovide patient informationand identify characteristicsassociated with the results. | Overall, 50% of the 1411scalp-cooled patients did notwear a head cover duringtheir last chemotherapysession.Patients were satisfied withthe results in 8% of cases afterTAC chemotherapy and up to95% after paclitaxeltreatment.Besides the type ofchemotherapy, higher doseand shorter infusion time,older age, female gender andnon-West-European type ofhair significantly increased theproportion head cover use.Hair length, quantity,chemical manipulation(dyeing, waving, coloring),wetting hair before scalpcooling, and treatment withchemotherapy ever before didnot influence the degree ofhead covering among | Scalp cooling results asrecorded in this openpatient registry werepositive for mostregimens, justifying its useby all eligible patients,except for those needingTAC.Lengthening infusion timemay improve the results. | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| patients. | |||||||
| van den Hurk, CJ,et al. (2013) | Review ofobservationalstudies,autopsystudies andMunich cancerregistry | Studies of skin andscalp skinmetastases inpatients with breastcancer withoutscalp cooling:studies of scalp skinmetastases in scalp-cooled patients with(mainly) breastcancer | Diverse | Using frequency data onmetastases in breast cancer todiscuss the risk of whetherscalp cooling might facilitatehiding and disseminating scalpskin metastases and thusdecrease survival. | The incidence of scalp skinmetastases in breast cancerpatients seems to becomparable for scalp-cooled(0.04-1%) and for non-scalp-cooled (0.03-3%) patients. | In patients with solidtumors, an unfavorabledevelopment of thedisease due to scalpcooling has never beendocumented.Scalp cooling can safely beoffered to patients treatedwith alopecia-inducingchemotherapy. | |
| Lemieux J, et al.(2015) | Retrospectivecohort | n=1370 womenwith non-metastaticbreast carcinomawho receivedchemotherapy inneoadjuvant(n=140) or adjuvantsetting (n=1230)n=553 used scalpcooling; n=817 weretreated in facilitieswhere scalp coolingwas not routinelyavailable | Not reported | To compare overall survivalaccording to whether or notscalp cooling was used duringneoadjuvant or adjuvantchemotherapy for non-metastatic breast cancer. | Median follow-up was 6.3years for scalp-cooled groupand 8.0 years for non-scalp-cooled group.No difference in overallmortality was observedbetween scalp-cooledpatients and non-scalp-cooledpatients (adjusted hazardratio 0.89, 95% confidenceinterval 0.68-1.17, p=0.40). | Among women undergoingneoadjuvant or adjuvantchemotherapy for non-metastatic breast cancer,scalp cooling used toprevent CIA had nonegative effect on survival. | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| Nangia J, et al.(2017)Clinicaltrials.govidentifierNCT01986140 | Randomized,multi-center(7)A comfortscale wasadministeredafter eachtreatment inscalp-coolinggroup.Alopeciaassessmentsusing CommonTerminologyCriteria forAdverseEvents(CTCAE) v4.0at baselineand afterchemotherapycycle by ablindedclinician,patient'sclinician andpatient;participants | n=182 women withstage 1 or II breastcancer undergoingchemotherapy fromDecember 2013 toSeptember 2016Randomized toreceive scalpcooling (n=119) orno cooling (n=63)Each patientunderwent scalpcooling for 30minutes pre-infusion, duringinfusion and 90minutes post-infusion | Planning to receive atleast 4 cycles of taxane-(n=91, 64%) and/oranthracycline-basedchemotherapy forcurative intent (n=51,36%) | To assess whether use of theOrbis Paxman Hair LossPrevention System is safe andeffective in reducing CIA inwoman with breast cancerundergoing neoadjuvant oradjuvant chemotherapy. | Publication reports on interimanalysis (n=142 patients);patients will be followed for 5years for safety (time and siteof first recurrence) and overallsurvival.48 of 95 (50.5%) in coolinggroup had successful hairpreservation (95% confidenceinterval 40.7%-60.4%)compared to 0 of 47 (0%) inthe control group (95%confidence interval, 0%-7.6%).Success rate difference was50.5% (95% confidenceinterval, 40.5%-60.6%).The trial was stopped early forsuperiority (p=0.0061).No statistically significantdifferences in changes in anyof the quality-of-life (QOL)scales from baseline tochemotherapy cycle 4 wereobserved between the scalpcooling and control groups.54 adverse events (all grades1 and 2) were reported in the | Among women with stageI to II breast cancerreceiving chemotherapywith a taxane,anthracycline, or both,those who underwentscalp cooling weresignificantly more likely tohave < 50% hair loss afterthe 4th chemotherapycycle compared with thosewho received no scalpcooling. | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| were asked ifthey neededto use a wigand/or a headwrap | |||||||
| Massey C (2004)Note: Data isincluded inPaxman UKClinical Study ofEfficacy | Open, non-randomized,observational,multi-center(8)Alopecia wasassessed usingthe WorldHealthOrganization(WHO) gradingsystem;patientacceptabilityassessed byquestionnaire;resultscompiled byScalp CoolingAssessmentGroups | n=94 breast cancerpatients whounderwenttreatment 1997-2000 | 5-fluorouracil,epirubicin andcyclophosphamide(FEC) regimen | To assess the efficacy of scalpcooling to reduce alopecia forwomen undergoing treatmentfor breast cancer using thePaxman Scalp Cooler.To assess patient views on thecomfort and acceptability ofscalp cooling using thePaxman Scalp Cooler. | Use of the Paxman ScalpCooler was judged a successfor 89% of all patients usingthe WHO grading system foralopecia and for 87% ofpatients being specificallyadministered the commonlyused 5-fluorouracil, epirubicinand cyclophosphamide (FEC)regimen.When asked about degrees ofcomfort during the scalp-cooling process, 85% ofpatients described it as verycomfortable, reasonablycomfortable or comfortable,with only 15% of patientsreporting a description ofuncomfortable or veryuncomfortable. | Scalp cooling using thePaxman Scalp Cooler wasfound to be an effectivetechnique with minimalside-effects for patientstreated with commonlyprescribed alopecia-inducing chemotherapydrugs. | |
| Bini M, et al. | Observational | N=47 breast cancer | 70% of patients | To verify effectiveness of | Median number of the | The Paxman scalp cooler | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| (2004) | single-centerNursescompletedquestionnaireon patients,chemotherapyand scalpcoolingcharacteristicsduring eachsession;results wereevaluatedindicating theseverity ofhair loss perCTCAE 3.0during eachchemotherapysession andpatient'ssatisfactionduring lasttreatment | patients whounderwenttreatment fromJune 2013-March2014Mean age: 53 years(range 35-72)46 female, 1 male80% were treatedin the adjuvantsetting andchemotherapy naïve | received anthracycline-basedpolychemotherapy (ACor FEC 75 every threeweeks), and 30%received monotherapywith taxanes on aweekly schedule | Paxman concerning alopeciain the sample group; evaluatepatients' expectation anddegree of final satisfactionwith regard to its use. | cooling session: 5 (range 1-12).Alopecia G0 and G1 wereregistered at the end ofchemotherapy in 62% of thepatients, irrespective of thetype of treatment.100% of patients reportedbeing satisfied in terms ofhair preservation during theirlast session.27% of patients discontinuedscalp cooling treatmentbecause of severe alopecia(G2); all these patients werereceiving an anthracycline.Scalp cooling was stoppedbecause of intolerance in11% of patients mainly dueto discomfort and longertime of infusion. | was found to be aneffective technique withmoderate side-effects forpatients treated withcommonly prescribedalopecia-inducingchemotherapy drugs.Lengthening infusion timeseems to be the main limitof this system. | |
| Falanga M, et al.(2010) | Observational,single-center | n=5 patients withbreast or non-smallcell lung cancerPatients complete | Single agent docetaxel | To determine efficacy andpatient compliance of scalpcooler Paxman of patientssubjected to single agent | The pilot study is ongoingwith 5 patients enrolled todate and 9 chemotherapycycles with the scalp cooler | Providing a means toreduce alopecia isimportant for patients forwhom this is a distressing | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| patient priorityscale forchemotherapy-related side effectsat baseline;patients treatedwith Paxman ScalpCooler for 30minutes pre-infusion and 45minutes post-infusion; patientquestionnairefollowing eachtreatment; hair lossevaluated by nursesapplying WHOcriteria at eachchemotherapy cycle | docetaxel for breast cancer ornon-small cell lung cancer; toreport on first Italianexperience. | support.Treatment has been welltolerated, with 1 case ofrefusal at treatment onsetand all others continuing withsuccessive chemotherapycycles. | and feared side effect,and studies arewarranted. Early data onpatient acceptance totherapy are encouraging.Data on patient symptompriority, efficacy andfurther data on tolerancewill be presented. | ||||
| El-saka RO, et al.(2009) | RandomizedPaxman ScalpCooler wasapplied 20minutes pre-infusion,duringinfusion andfor 2 hours | n=120 femalebreast cancerpatients treated inadjuvant setting,July 2007-August2008Patients wererandomized forscalp cooling during | Doxorubicin (50 mg/m2), 5-FU (500 mg/m2) andcyclophosphamide (500 mg/m2) for 6 cycles | To evaluate the role of scalpcooling in reducinganthracycline-induced hairloss and its impact on QOL. | After 4 cycles, 61.7 % ofpatients in the scalp coolinggroup had grade 4 hair losscompared to 81.7 % ofpatients in control group.After 6 cycles, 85% ofpatients in scalp coolinggroup experienced grade 4hair loss compared to 100% | The role of scalp cooling islimited at the total doseof 300 mg/m2doxorubicin. It may bemore effective with fewercycles or less aggressivedrug combination.Hair loss affects variousaspects of QOL, especially | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| post-infusion;hair lossassessed usingWHO criteriaat each cycleand after 6chemotherapycycles; QOLwas assessedusing theEuropeanOrganizationfor ResearchandTreatment ofCancer(EORTC) QLQ-C30 and BR23 | chemotherapy(n=60) or not (n=60) | of patients in the controlgroup.9 patients (15%) in the scalpcooling group developedgrade 1-2 hair loss.No significant relation wasfound between degree ofhair loss and liver functiontests.73.3% of patients werecomfortable during cooling.QOL scores were comparablebetween groups except foremotional functioning andbody image. In the hair lossgroup, 71.2% of patientsshowed severe disturbanceof emotional functioning and54.1% of patients hadmoderate disturbance inbody image. In hairpreservation group (9patients), 77.8% developedmoderate disturbance ofemotional functioning and allpatients had mild disturbance | emotional functioning andbody image. More time isneeded to assess the long-term effect of hair loss onQOL and the incidence ofscalp metastasis in thetwo study groups. | ||||
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| in the body image. | |||||||
| Betticher DC, etal. (2013)Note: Study datais reported inPaxman SwissClinical Studiesof EfficacyClinicaltrials.govidentifierNCT01008774 | Open-label,prospective,non-randomized | n=238 patients withsolid tumorsreceivingchemotherapy in apalliative settingPatients allocatedper theirpreference; n=128Paxman, n=77 coolcap, n=39 nocoolingTypes of cancer:breast n=76, lungn=86, prostaten=86, other n=38 | Docetaxel (55–60mg/day on weeklytherapy, 135–140mg/day on 3-weeklytherapy) | To investigate whether twodifferent methods of scalpcooling can prevent hair loss,i.e. Paxman PSC-2 machineand cold cap.Primary endpoint wasincidence of WHO grade III orIV alopecia as assessed bytreating physician or wearinga wig.Additional endpointsconsisted of discontinuationof initially chosen alopeciaprevention method, numberof cycles of chemotherapyreceived in each subgroup,patient perception of scalpcooling procedures, well-being, and tolerability/sideeffects of scalp coolingsystems. | Median number of cycles andmedian docetaxel doses weresimilar across groups.Alopecia occurrence under 3-weekly docetaxel- Paxman: 23%- Cold cap: 27%- No cooling: 74%.Alopecia occurrence underweekly docetaxel- Paxman: 7%- Cold cap: 8%- No cooling: 17%.Cooling (Paxman and cold capcombined) reduced alopeciarisk by 78% (hazard ratio 0.22,95% confidence interval 0.12-0.41).5% patients reported adverseevents (most frequentlysensation of cold).30 (13%) patientsdiscontinued coolingmeasures after 1 cycle. | Both Paxman scalp coolingand cold cap offerefficacious protectionagainst hair loss, inparticular when docetaxelis administered in a 3-weekly interval.There appears to be nodifference between scalpcooling with Paxman orcold cap in terms ofefficacy and tolerability. | |
| Author | Type of Study/ | Patients | Chemotherapy Agents | Objective | Results | Conclusion | |
| Method | (Performance and Safety) | ||||||
| Kurbacher CM,et al. (2017) | Retrospectiveanalysis | n=99 femalepatients whounderwent sensor-controlled scalpcooling alongsidechemotherapy from2014-2016Types of cancer:breast n=78,epithelial ovariancarcinoma n=15,other n=6Curative intentn=72, palliativesetting n=27Chemotherapynaïve n=66, priorchemotherapyn=33Pre-menopausaln=48, post-menopausal n=51 | Anthracycline-basedn=4, taxane-basedn=29; AT-based n=51,other n=15 | To obtain detailedinformation about theeffectiveness and safety ofsensor-controlled scalpcooling using the Paxmansystem in female patientsexposed to CIA-inducingchemotherapy for breastcancer or genital tractmalignancies in the clinicalroutine. | 69 (69.7%) patientscompleted sensor-controlledscalp cooling, of which 58(58.6%) experienced completehair preservation (DS 0) and11 (11.1%) showed partialsuccess (DS 1-2).30 (30.3%) patientsdiscontinued sensor-controlled scalp cooling.21 (21.2%) patientsdiscontinued for CIA, 4 (4.0%)headache, 3 (3.0%) localdiscomfort/"feeling cold", 2(2.0%) unknown.Side effects were all notsevere and resolvedcompletely after cessation ofsensor-controlled scalpcooling. | In the clinical routine,sensor-controlled scalpcooling to prevent CIA inpatients with breast orfemale genital tract canceris feasible, safe, andeffective.Study success rate is ingood agreement toprevious reports althoughmore patients in thepalliative setting or with ahistory of priorchemotherapy have beenincluded. | |
| Silva G, et al.(2016) | ObservationalPhotographyandassessment ofhair loss byCTCAE v4.0; | n=20 femalepatients followedsince 2015Median age: 51yearsTypes of cancer: | Most commontreatments weredocetaxel-cyclophosphamide(25%) and doxorubicinand cyclophosphamidefollowed by paclitaxel - | To evaluate scalp coolingresults in preventing CIA in aprivate clinic in Brazil, usingthe Paxman Orbis scalpcooling machine. | 7 (35%) patients had successwith alopecia G1.5 (25%) patients discontinuedscalp cooling; of these, 3 of 5patients discontinuedsecondary to hair loss, all | Scalp cooling is tolerableand has been showinggood results in preventingCIA in our patients.Patients AC/T receiversremain challenging. | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| discomfortwas assessedby Pain VisualAnalogueScale | breast (90%), n=2patients hadmetastatic tumors | AC/T (25%) | from AC/T group.7 patients (35%) are stillunder scalp coolingtreatment; 2 of 7 patientswith alopecia G2.56% of patients complainedof headache with a medianvisual analog pain score of 4. | ||||
| Boyle F, et al.(2015) | Focus groupor semi-structuredinterviewParticipantperceptionsandexperiences ofscalp coolingwerediscussed aspart ofpatients'overallchemotherapyexperienceand athematicanalysis | n=17 women withbreast cancerScalp-cooled(Penguin ColdCaps®, DignitanaDignicaps® orPaxman Orbis®caps) and non-scalped-cooledparticipant viewswere sought | Largely adjuvant TC orFEC-D | To explore breast cancerpatients' perceptions andexperience of scalp cooling,and their needs forinformation.Provide first exploration ofAustralian patient attitudes toscalp cooling. | Scalp cooling was perceived asa proactive way of managinghair loss.5 main themes: (1) scalpcooling in the context oftreatment decision-makingdiscussions (2) hair lossexpectations vs experiences(3) treatment expectations vsexperiences (4) potential forfaster regrowth, and (5)satisfaction with scalp cooling.Accurate information duringtreatment decision-makingwas primary factor influencingpatient expectations andsatisfaction.Faster regrowth was a | Evidence-basedinformation duringtreatment decision-makingis essential to ensurepatient expectations areconsistent with currenttreatment outcomes.Additional information andeducation tools areneeded to assist patientsand health careprofessionals managescalp cooling, and will bedeveloped. | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| conducted | motivator to continuetreatment.Efficacy and tolerability ofscalp cooling influencedfuture hypothetical treatmentdecision-making for allparticipants.Information regardingtolerability and hair careduring treatment influencedanxiety. | ||||||
| Kinoshita T, et al.(2015) | Case reviewHair loss wasgraded usingthe WHOclassificationscheme | n=21 female breastcancer patientsAC therapy n=11,TC therapy n=10 | Patients werescheduled to receive 4cycles of post-operative adjuvantchemotherapy usingeither AC(60/600mg/m²) or TC(75/600mg/m²) | To confirm the efficacy of hairloss prevention and the safetyof scalp cooling equipment,and thus enhance patientrecovery and QOL.The primary outcome was theproportion of patients able tocomplete 4 cycles of post-operative adjuvant AC or TCtherapy.Secondary outcomes were thedegrees of comfort,satisfaction, and hair lossprevention, as well as therates of adverse events andmetastases to the scalp in | 9 (81.8%) cases in the ACtherapy group and 10 (100%)cases in the TC therapy groupcompleted the protocol.WHO grades:AC therapy, Grades 0-4:0, 3, 2, 5, 1TC therapy, Grades 0-4:0, 3, 3, 4, 011 of 21 (52.4%) patientsexperienced Grade 1-2 hairloss, i.e. 5 of 11 (45.5%)patients in the AC group and 6of 10 (60%) patients in the TCgroup. | We will continue studyingthe effects of scalp coolingin breast cancer patientsundergoing chemotherapy,and work to improve onthe design of the originalscalp cooling equipment. | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| patients who used the scalpcooling equipment, i.e.Paxman Cooler. | Scalp cooling resulted ingreater hair loss preventionduring TC therapy than ACtherapy. | ||||||
| Hussain O, et al.(2015) | In vitro testing | Not applicableHaCaT cells culturedin serum freeconditions weretreated withchemotherapyagents; drug-induced cytotoxicityfollowing treatmentat physiologicaltemperature (37°C)and coolingconditions (max22°C) wasdetermined at 72hours post-treatment | Range ofconcentrations of 5-fluorouracil, epirubicinand paclitaxel; TAC(docetaxel,doxorubicin andcyclophosphamide),FAC [5-fluorouracil (5-FU), doxorubicin andcyclophosphamide]and FEC (5-FU,epirubicin andcyclophosphamide) ascombinatorialtreatments | To use in vitro keratinocytemodels to study the effect ofTAC, FAC and FEC on cellviability and determinewhether cooling can protectfrom combinatorial drug-induced cytotoxicity. | Combinatorial drugtreatments TAC, FEC and FACare more cytotoxic incomparison to individualchemotherapy drugs.Cooling demonstrated theability to protect very wellfrom individual drug-inducedcytotoxicity (e.g. 5-FUassociated toxicity), whilstshowing differential ability toprotect from combinatorialdrug-induced cytotoxicity. | The similarity of our invitro data with clinicalobservations providesbiological support for thecytoprotective role of scalpcooling as well as evidencethat, despite theirreductive nature, our invitro models arebiologically relevant. | |
| Letchford DB, etal. (2016) | OngoingprospectivecohortDegree of hairloss wasassessed using | n=20 consentingpatients whounderwent scalpcooling using thePaxman Orbis IIdevice during | 11 varyingchemotherapyregimens includingFEC, FEC-D, pacitaxel,carboplatin/paclitaxeland TCH | To report preliminary resultsfrom ongoing prospectivecohort study of scalphypothermia in theprevention of CIA. | Six patients withdrew due tograde 2/3 alopecia.3 patients that completedtreatment with scalp coolingdeveloped grade 2 alopecia. | Interim results suggestscalp hypothermia usingmodern scalp coolingsystems represents a safeand effective method ofreducing rates of CIA. | |
| Author | Type of Study/Method | Patients | Chemotherapy Agents | Objective | Results(Performance and Safety) | Conclusion | |
| the WHO andDeansalopecia scale,digitalphotographyand patientself-reportingquestionnaire | treatmentEach patientunderwent scalpcooling for 30minutes pre-infusion, duringinfusion and 90minutes post-infusion | 6 patients treated so far withFEC (as part of the FEC-Dprotocol) or weekly paclitaxeldeveloped grade 2/3alopecia.4 patients treated withcarboplatin/ paclitaxel or TCHcompleted treatment witheither grade 1 or no alopecia.5 patients withdrew due todiscomfort, but otherwise noadverse effects wereassociated with scalp cooling. | Further clinical trials arerequired to indicate whichpatients/chemotherapyregimens will obtainmaximal efficacy fromscalp hypothermia inpreventing CIA. | ||||
| StudyDescription | Type of Study/ Method | Patients | Chemotherapy Agents | Scalp Cooling Times | Results | ||
| Dutch Registry(presented at2017MASCC/ISOOInternationalMeeting)Note: 2006-2010registry data isincluded in vanden Hurk et al.(2012) andPaxmanNetherlandsClinical Study ofEfficacy/3 | Registry | 2006-2010: n=1411(4% male)2010-2015: n=4864(14% male)2015-2017: n=827(19% male)Types of cancer:breast 75%,prostate 8%,ovarian 6%,stomach/colon/liver5%, lung 3%, other2% | AC/AC-T/AC-D2006-2010: 140/1411 (10%)2010-2015: 941/4864 (19%)2015-2017: 329/827 (40%)FEC/FEC-D/ FEC-T2006-2010: 798/1411 (57%)2010-2015: 1386/4864 (28%)2015-2017: 66/827 (8%)Jevtana2006-2010: 0/1411 (0%)2010-2015: 42/4864 (1%)2015-2017: 6/827 (1%)Eribuline2006-2010: 0/1411 (0%)2010-2015: 0/4864 (0%)2015-2017: 6/827 (1%) | Not reported | Results of 2006-2013 registryChemotherapyagent (s)AC/AC-T/AC-DDocetaxelFEC/FEC-D/FEC-TFACTaxol(wkl/3wkl)TACTCarIrinotecan | No.patients10798432192101556167475267 | Positive result ofscalp cooling61%87%44%46%82%11%57%31% |
| Paxman UKClinical Study ofEfficacyNote: Data isincluded inMassey CS, et al.(2004) | Open, non-randomized,observational,multi-center(8)Patientscompletedquestionnairesrelated to | n=95 breast cancerpatients beingtreated withchemotherapy inadjuvant orpalliative settingbetween 1997-2000Mean age: 44 years | Epirubicin as monotherapy(n=10), FEC combinationtherapy used 1997-2000(n=62), doxorubicin asmonotherapy or combination(n=11), docetaxel single agent(n=5), CMF (n=5), notreported (n=2) | Pre-infusion: 15-20minutesDuring infusion: coolingwas maintainedPost-infusion: 120minutes for majority ofpatients | 5 of 95 (5.3%) total patients observed grade 3 hair loss1 of 95 (1.1%) total patients observed grade 4 hair loss5 of 95 (5.3%) patients discontinued scalp cooling treatment2 of 62 (3.2%) patients receiving FEC observed grade 3 hair loss1 of 62 (1.6%) patients receiving FEC observed grade 4 hair loss |
Table 5B – Published Clinical Studies of the Paxman Scalp Cooler
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Table 5C – Non-Published Clinical Studies of the Paxman Scalp Cooler
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| StudyDescription | Type of Study/ Method | Patients | Chemotherapy Agents | Scalp Cooling Times | Results |
|---|---|---|---|---|---|
| comfort andacceptabilityof scalpcooling | (range 28-61) | 11% of 95 total patients and 13% of 62 patients treatedspecifically with FEC required wigs85% of patients reported that they were comfortable,reasonably comfortable, or very comfortable during thescalp cooling period12% of patients reported they were uncomfortable with anadditional 3% very uncomfortableOnly 5% of patients discontinued scalp cooling before theend of chemotherapy treatment, with discontinuationbecause of discomfort seen in one patientHeadaches at some time during treatment cycles werereported in 32% of patients | |||
| PaxmanNorwegianClinical Study ofEfficacy | Observational,single-centerPatients viewsrelated tocomfort andacceptabilityof scalpcooling werecollated bycontact nurse | n=54 breast cancerpatients treated inneo-adjuvant,adjuvant orpalliative settingsbetween 2000-2001Mean age: 44 years(range 28-61) | FEC/FAC — epirubicin orpaclitaxel | Pre-infusion:FEC/FAC: median20 minutes (range15-50)Paclitaxel: median20 minutes (range15-120)During infusion: coolingwas maintainedPost-infusion:FEC/FAC: median।120 minutes (range120-150) | 8% of patients experienced significant hair loss89% of patients described scalp cooling as acceptable, withminimal discomfort caused by the longer treatment period15% of patients considered coldness to be a major problem2% of patients considered headaches to be a major problemOne patient discontinued treatment because of discomfortAuthors concluded scalp cooling is an effective method foravoiding alopecia in patients receiving FEC or weeklypaclitaxel |
| StudyDescription | Type of Study/ Method | Patients | Chemotherapy Agents | Scalp Cooling Times | Results |
| Paclitaxel: median60 minutes (range60-120) | |||||
| PaxmanNetherlandsClinical Study ofEfficacy/1 | Observational,multi-center(13 of which 2did not havescalp coolingavailable)Patientscompletedquestionnairesrelated tocomfort andacceptabilityof scalpcooling;observationalstudy wasscored usingthe WHO &visualanalogue scalesystems | Scalp-cooled(n=160) and non-scalp-cooled (n=86)patients withseveral types ofcancers | Taxane and/or anthracycline-based chemotherapy (n=184)FEC regimen used 1997-2002(n=62) | Pre-infusion: 30minutesDuring infusion: coolingwas maintainedPost-infusion: 90minutes for majority ofpatients | A head cover was used by 51% of scalp-cooled patients38% of scalp-cooled patients were thought to havepurchased a wig needlessly40% reduction in the use of head covers |
| PaxmanNetherlandsClinical Study of | Non-randomized(Phase I), | n=166 cancerpatients | 3-weekly docetaxel | Pre-infusion: 30minutes | A reduction in scalp cooling time to 45 minutes, did notreduce the effectiveness of the Paxman Scalp CoolingSystem in preventing hair loss in docetaxel treated cancer |
| StudyDescription | Type of Study/ Method | Patients | Chemotherapy Agents | Scalp Cooling Times | Results |
| Efficacy/2 | randomized(phase II),multi-center(11)Patients viewsrelated tocomfort andacceptabilityof scalpcooling werecollated bycontact nurse | Types of cancer:breast 49%,prostate 33%, lung23%Mean age: 44 years(range 35-79) | During infusion: coolingwas maintainedPost-infusion:- Phase I: 90 minutes- Phase 2: 90 vs. 45minutes | patientsNo head cover or wig required in 88% of patients following45 minutes post-infusion cooling after 3-weekly docetaxelcompared with 74% after 90 minutes post-infusion coolingHeadaches were only reported in 20% of patients, with only5% of patients discontinuing scalp coolingVisual analogue scale: mean score = 69 (0 = bad, 100 =good)Headache: 80% no headaches; 13% mild headaches and 7%moderate/severe headaches5% of patients discontinued scalp cooling because ofintolerance | |
| PaxmanNetherlandsClinical Study ofEfficacy/3Note: Study datais included in vanden Hurk, CJ, etal. (2012) | Observational | n=1411 patientswith range of cancertypes | A60C600 (AC) (n=74),A60C600/D100 (ACD) (n=16),ACT overall (n=50),D75A50C500 (TAC) (n=66), Doverall (n=120), F500A50C500(FAC) (n=39), FEC overall(n=752), F500E100C500/D100(FE100CD) (n=46), TCarbooverall (n=68), T70-90 (42),Irino 250 (n=42), other (n=64) | Not reported | Success rates (no wig or head cover required) variedaccording to regimen48% mean success rate (range 8-80%)Study demonstrates effectiveness of the Paxman ScalpCooling System in the prevention of chemotherapy inducedhair loss with widely used chemotherapy dosages andregimensHigh levels of comfort and patient acceptability werereported in all trials, with low numbers of patientsdiscontinuing scalp coolingBesides the type of chemotherapy, higher dose and shorterinfusion time; older age, female gender and non-western |
| StudyDescription | Type of Study/ Method | Patients | Chemotherapy Agents | Scalp Cooling Times | Results |
| European types of hair increased the proportion of headcoverHair length, quantity, chemical manipulation and treatmentwith chemotherapy ever before, did not influence degree ofhead covering among patients | |||||
| Paxman SwissClinical Studiesof EfficacyNote: Data isincluded inBetticher et al.(2013) | Non-randomized,prospective,controlled,multi-center(27) | n=238 patients withseveral types ofcancer includingbreast, lung,prostate, otherswho underwenttreatment July2009-October 2011n=128 patientstreated withPaxman ScalpCooling System;n=71 treated withgel caps (cold caps);n=39 received nocooling treatment | All patients except 1 receiveddocetaxel chemotherapy,alone or in combination withother agents | Paxman Scalp CoolingPre-infusion: 15minutesDuring infusion: coolingwas maintainedPost-infusion: 90minutes (45 minutesaccording to amendedtemperature)Cold capPre-infusion: 15minutesDuring infusion: coolingwas maintainedPost-infusion: 90minutes (45 minutesaccording to amendedtemperature)Gel caps have to beexchanged after the | Kaplan-Meier estimate to reach the combined end point(alopecia WHO III/IV and/or wearing a wig) showing PaxmanScalp Cooling Systems and gel caps have a significantlyreduced risk of alopecia by 78%On a six-point scale (1=good to 6=bad) with respect toglobal impression of therapy, patients at study end reportedthe following: Paxman 4.5 ± 1.6, gel cap 4.6 ± 1.4, no cooling4.1 ± 1.9; respective grading marks were similar in the threegroupsRisk of alopecia is significantly reduced (70%) when usingeither the Paxman Scalp Cooling System or gel capcompared to no coolingIn particular, alopecia is reduced by these two coolingdevices when docetaxel is administered every 3 weeks |
| StudyDescription | Type of Study/ Method | Patients | Chemotherapy Agents | Scalp Cooling Times | Results |
| first 25 minutes oftreatment, afteranother 45 minutes,and every 60 minutesthereafter | |||||
| PaxmanLebanese ClinicalStudies ofEfficacy | Open, non-randomized,observational,multi-center(10) | n=91 cancerpatients whounderwenttreatment March2012-April 2013 | Docetaxel 80-130mg asmonotherapy or combination;TAC; Doxorubicin100mg/Endoxan 1000mg;Taxotere 100mg + Herceptin;Taxol 120-140mg; Taxol120mg/Carboplatin; FEC;Alimta 700mg + Carboplatin300mg; FAC; TCH; VP 16Etoposide; Taxol/Cisplatin,Herceptin; MTX 100mg -Doxorubicin 80mg;Doxorubicin 50mg,Dacarbazine 550mg; Gemzar1600mg + Carboplatin | Pre-infusion: 90minutesDuring infusion: coolingwas maintainedPost-infusion:dependent upon drugdosage (range 120-360minutes) | 91.21% overall scalp cooling had excellent results6 of 91 patients underwent treatment with TAC, 6/6 (100%)patients showed no signs of hair lossSeverity of chemotherapy-induced alopecia has beenreduced greatly by using the Paxman Scalp Cooling System,with only 5 of 91 (5.5%) patients not responding well tohead coolingStudy demonstrates effectiveness of the Paxman ScalpCooling System on a variety of anti-cancer treatmentsIt should be noted that the difference in climate, nature ofskin and types of hair amongst European andMediterranean, makes a difference with pre/post-infusiontimes |
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Chemotherapy and Abbreviations
A: doxorubicine Carbo: carboplatin C: cyclophosphamide CMF: cyclophosphamide, methotrexate and 5-fluorouracil D: docetaxel E: epirubicine F: 5-fluorouracil (5-FU) H: herceptin Irino: irinotecan MTX: methotrexate T: paclitaxel
15. Bibliography
Published Clinical Studies
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- CJ van den Hurk et al. Scalp cooling for hair preservation and associated characteristics in 1411 chemotherapy patients - results of the Dutch Scalp Cooling Registry. Acta oncologica (Stockholm, Sweden). 51, 497-504 (2012).
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- CJ van den Hurk, LV van de Poll-Franse, WP Breed, JW Nortier. Scalp cooling to prevent alopecia after chemotherapy can be considered safe in patients with breast cancer. Breast (Edinburgh, Scotland). 22, 1001-1004 (2013).
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- J Lemieux et al. No effect of scalp cooling on survival among women with breast cancer. Breast cancer research and treatment. 149, 263-268 (2015).
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- J Nangia et al. Effect of a Scalp Cooling Device on Alopecia in Women Undergoing Chemotherapy for Breast Cancer: The SCALP Randomized Clinical Trial. Jama. 317, 596-605 (2017).
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- CS Massey. A multicentre study to determine the efficacy and patient acceptability of the Paxman Scalp Cooler to prevent hair loss in patients receiving chemotherapy. European journal of oncology nursing: the official journal of European Oncology Nursing Society. 8, 121-130 (2004).
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- M Bini, A Borriello, C Crivellaro, E Gianotti, G Greco, B Lugli, G Razzini, A Righi, S Rossi. Scalp Cooler: Un Metodo Per Ridurre L'alopecia Da Chemioterapia. AllAO National Congress. 2014 May 29-31.
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- M Falanga, J Bryce, P Maione, C Gridelli. Introduction of a scalp-cooling system Paxman for hair loss prevention: An Italian experience. Supportive Care in Cancer. 18, S126 (2010).
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- RO El-saka, G El-Husseiny, Y Rostom, A Salama. Scalp cooler efficacy to reduce anthracyclineinduced alopecia and its QOL impact in breast cancer. Journal of Clinical Oncology. 27:15 Supplement 1, e13539 (2009).
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- DC Betticher et al. Efficacy and tolerability of two scalp cooling systems for the prevention of alopecia associated with docetaxel treatment. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer. 21, 2565-2573 (2013).
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- CM Kurbacher, S Herz, G Kolberg, N Kettelhoit, AT Kurbacher, C Schweitzer, K Theisen, JA Kurbacher. Sensor-controlled scalp cooling in the clinical routine: an effective and safe method to prevent chemotherapy-induced alopecia in women with breast or female genital tract cancer. European Journal of Cancer. 72, Supplement 1, S167-S168 (2017).
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- G Silva, A Pires, C Yamamoto, S Simon. Scalp cooling as a preventive method of chemotherapy-induced alopecia: Experience of a private clinic in Sao Paulo, Brazil. Supportive Care in Cancer. 24:1 Supplement 1, S186-S187 (2016).
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- F Boyle et al. Scalp cooling: A qualitative study to assess the perceptions and experiences of Australian patients with breast cancer. Asia-Pacific Journal of Clinical Oncology. 11, 43 (2015).
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- T Kinoshita et al. Scalp cooling system to prevent hair loss in breast cancer patients receiving chemotherapy. Breast (Edinburgh, Scotland). 24 Supplement 1, S59 (2015).
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- O Hussain, W Al-Tameemi, C Dunnill, A Collett, N Georgopoulos. Effect of cooling on cytotoxicity by monotherapy versus combinatorial chemotherapy in keratinocytes. Breast (Edinburgh, Scotland). 24 Supplement 1, S47-S48 (2015).
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- DB Letchford, K Baxter, SD Begbie, W Faisal. Preliminary results from an ongoing prospective cohort study of scalp hypothermia in the prevention of chemotherapy-induced alopecia in rural New South Wales. Asia-Pacific Journal of Clinical Oncology. 12 Supplement 5, 125 (2016).
Non-Published Clinical Studies
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- Advances in scalp cooling research from the Netherlands. Multinational Association of Supportive Care in Cancer/ International Society of Oral Oncology (MASCC/ISOO). Annual Meeting. 2017 June 22-24, Washington DC.
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- Paxman UK Clinical Study of Efficacy
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- Paxman Norwegian Clinical Study of Efficacy
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- Paxman Netherlands Clinical Study of Efficacy/1
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- Paxman Netherlands Clinical Study of Efficacy/2
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- Paxman Netherlands Clinical Study of Efficacy/3
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- Paxman Swiss Clinical Studies of Efficacy
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- Paxman Lebanese Clinical Studies of Efficacy
§ 878.4360 Scalp cooling system to reduce the likelihood of chemotherapy-induced alopecia.
(a)
Identification. A scalp cooling system to reduce the likelihood of chemotherapy-induced alopecia is a prescription device intended to reduce the frequency and severity of alopecia during chemotherapy in which alopecia-inducing chemotherapeutic agents are used.(b)
Classification —Class II (special controls). The special controls for this device are:(1) Non-clinical performance testing must demonstrate that the device meets all design specifications and performance requirements, and that the device performs as intended under anticipated conditions of use. This information must include testing to demonstrate accuracy of the temperature control mechanism.
(2) Performance testing must demonstrate the electromagnetic compatibility and electrical safety of the device.
(3) Software verification, validation, and hazard analysis must be performed.
(4) The patient contacting components of the device must be demonstrated to be biocompatible. Material names must be provided.
(5) Labeling must include the following:
(i) A statement describing the potential risk of developing scalp metastasis.
(ii) Information on the patient population and chemotherapeutic agents/regimen for which the device has been demonstrated to be effective.
(iii) A summary of the non-clinical and/or clinical testing pertinent to use of the device.
(iv) A summary of the device technical parameters, including temperature cooling range and duration of cooling.
(v) A summary of the device- and procedure-related adverse events pertinent to use of the device.
(vi) Information on how the device operates and the typical course of treatment.
(6) Patient labeling must be provided and must include:
(i) Relevant contraindications, warnings, precautions, and adverse effects/complications.
(ii) Information on how the device operates and the typical course of treatment.
(iii) Information on the patient population for which there is clinical evidence of effectiveness.
(iv) The potential risks and benefits associated with use of the device.
(v) Postoperative care instructions.
(vi) A statement describing the potential risk of developing scalp metastasis.