Regional Cooling

Regional Cooling

PEP Topic 
Skin Reactions
Description 

Regional cooling involves the application of ice packs to the wrists and ankles during chemotherapy infusion. As with cryotherapy, cooling is theorized to cause vasoconstriction and decreased circulation of the chemotherapeutic drug in the regional area, less extravasation into surrounding tissue, and a resulting reduction in cutaneous toxicity. Regional cooling has been evaluated in patients with cancer for the prevention of palmar-plantar erythrodysesthesia (PPE), a skin effect. Cryotherapy, based on the same theory, has been used for the prevention of mucositis.

Effectiveness Not Established

Research Evidence Summaries

Mangili, G., Petrone, M., Gentile, C., De Marzi, P., Vigano, R., & Rabaiotti, E. (2008). Prevention strategies in palmar-plantar erythrodysesthesia onset: The role of regional cooling. Gynecologic Oncology, 108, 332–335.

doi: 10.1016/j.ygyno.2007.10.021
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Study Purpose:

To evaluate the effectiveness of strategies to prevent ​palmar-plantar erythrodysesthesia (PPE) incidence, including regional cooling, behavioral rules, and lower-dose pegylated liposomal doxorubicin (PLD), in patients with gynecologic malignancies.

Intervention Characteristics/Basic Study Process:

PLD doses ranged from 30 to 50 mg/m2 every 21 to 28 days. All patients received premedication with oral dexamethasone 8 mg (12 hours before PLD) and pyridoxine 300 mg PO daily. All patients were advised to follow strict behavioral rules: keep skin well hydrated, avoid sunlight, minimize trauma to the hands and feet, avoid contact with warm water, and avoid hot foods and liquids. Patients who were enrolled from 2001 to December 2003 were in the non–regional cooling group (n = 25), whereas patients who were enrolled from January 2004 to 2006 were in the regional cooling group (n = 28). Patients received regional cooling (application of ice packs around wrists and ankles) and icicles during PLD infusion.

Sample Characteristics:

  • The study reported on a sample of patients who received PLD as a single therapy (n = 33), PLD plus carboplatin (n = 17), or PLD plus paclitaxel (n = 3).
  • All patients were women with gynecologic cancers (N = 53).

Setting:

Obstetrical/Gynecological Department at San Raffaele Hospital in Milan, Italy

Study Design:

This was a prospective, observational, single-center, nonrandomized study.

Measurement Instruments/Methods:

Skin toxicity was graded according to National Cancer Institute (NCI) and Gynecologic Oncology Group (GOG) criteria.

Results:

The incidence of PPE was significantly higher in the non–regional cooling group (n = 9, 36%) compared to the regional cooling group (n = 2, 7%; p = 0.0097).

Conclusions:

Multivariant analysis revealed the use of a regional cooling protocol and lower PLD dosage were significant factors in reducing the onset and incidence of PPE. The authors estimated the probability of developing PPE in a patient who receives 30 to 35 mg/m2 of PLD and follows the regional cooling protocol is 1.42%. Conversely, a patient who does not adapt this regional cooling protocol and receives 40 to 50 mg/m2 of PLD every three weeks has a 60.41% estimated probability of developing PPE.

Limitations:

  • The sample size was small.
  • This was a prospective, observational, nonrandomized study. Efficacy needs to be proven in a controlled and randomized study.
  • A combination of interventions was used in this study. All patients were given oral dexamethasone and oral pyridoxine as premedication. Therefore, determining the effectiveness of the individual interventions is difficult.

Molpus, K.L., Anderson, L.B., Craig, C.L., & Puleo, J.G. (2004). The effect of regional cooling on toxicity associated with intravenous infusion of pegylated liposomal doxorubicin in recurrent ovarian carcinoma. Gynecologic Oncology, 93, 513–516.

doi: 10.1016/j.ygyno.2004.02.019
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Study Purpose:

To evaluate the effectiveness of regional cooling on palmar-plantar erythrodysesthesia (PPE).

Intervention Characteristics/Basic Study Process:

Patients received pegylated liposomal doxorubicin (PLD) every 28 days, with dosages ranging from 30 mg/m2 to 50 mg/m2.

Group 1 (n = 17) used regional cooling. The regional cooling protocol (RCP) included administration of ice packs to the wrists and ankles, and iced liquids were available for consumption during PLD infusion. In addition, patients were encouraged to use the ice packs for up to 24 hours after completion of the PLD infusion.

Group 2 (n = 3) did not use RCP. Patients were instructed to avoid ingestion of hot foods or liquids, avoid contact with hot water and direct sunlight, and minimize friction to the hands and feet for 72 hours post-PLD treatment.

Sample Characteristics:

  • The study reported on a sample of 20 female patients with recurrent epithelial ovarian cancer who received PLD.
  • The median number of PLD cycles was five.

Setting:

University of Nebraska Medical Center in Omaha

Study Design:

This was a retrospective analysis of 20 patients’ records.

Measurement Instruments/Methods:

PPE was graded from 1 to 4; however, the authors did not specify what grading system was used.

Results:

The frequency and severity of PPE was reduced in 17 women who used the RCP, compared to three women who did not use those measures (p = 0.047).

Conclusions:

Regional cooling around the wrists and ankles was well tolerated and had a high degree of compliance during chemotherapy administration.

Limitations:

  • This was a retrospective review of records.
  • The sample size was small.
  • The description of the measurement method used to grade PPE symptoms was insufficient; reliability and validity were unclear.

Scotte, F., Banu, E., Medioni, J., Levy, E., Ebenezer, C., Marsan, S., . . . Oudard, S. (2008). Matched case-control phase 2 study to evaluate the use of a frozen sock to prevent docetaxel-induced onycholysis and cutaneous toxicity of the foot. Cancer, 112, 1625–1631. 

doi: 10.1002/cncr.23333
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Study Purpose:

To assess the efficacy and safety of cold therapy in the prevention of docetaxel-induced onycholysis and skin toxicity of the foot

Intervention Characteristics/Basic Study Process:

Patients wore an Elasto-Gel (Akromed, France) flexible frozen sock (FS) containing glycerin, which has thermal properties that allow its use in cold or hot therapies. The FS covered participants' right foot up to the ankle. The FS was refrigerated for at least three hours at –250 C to –300 C. The FS was worn at each docetaxel infusion for a total of 90 minutes (from 15 minutes before administration to 15 minutes postdocetaxel hourly infusion). Two FSs were used successively (45 minutes each) to maintain coolness. The left foot was not protected and acted as the control.

Sample Characteristics:

  • N = 48   
  • MEDIAN AGE = 62 years (range = 36–80 years)
  • MALES: 36 (75%), FEMALES: 12 (25%)
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: Variety of tumor types; undergoing docetaxel at 70–100mg /m2 every three weeks for one-hour infusions, alone or in combination therapy
  • OTHER KEY SAMPLE CHARACTERISTICS: No prior taxane therapies, absence of skin and nail disorders, life expectancy of at least three months and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. All patients provided written informed consent.

Setting:

  • SITE: Single site   
  • SETTING TYPE: Not specified    
  • LOCATION: French center

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment
  • APPLICATIONS: Elder care

Study Design:

Prospective, convenience, case-controlled, phase II study of 50 consecutive patients (unblinded)

Measurement Instruments/Methods:

  • Two-sample Wilcoxon matched-pairs rank test adjusted for tied values to determined statistical difference
  • Kaplan–Meier and log-rank methods were used to estimate and compare differences in time to toxicity occurrence.
  • Common Terminology Criteria for Adverse Events (CTCAE), version 3, for onycholysis and skin toxicity
  • Four-point satisfaction scale for patient comfort

Results:

The FSs led to a significant reduction in nail toxicity with 0% versus 21% (p = 0.002). Overall skin toxicity existed in 2% of FS-protected feet but only 6% of others, which was insignificant (p = 0.18). Time until nail toxicity occurrence for an unprotected foot was associated with the number of cycles (HR of 0.36, 95% confidence interval [0.17, 0.77], p = 0.008). Fifty-eight percent were satisfied and even very satisfied (19%) with the FS protection. Only 2% of patients were dissatisfied because of FS-related cold intolerance.

Conclusions:

Cold therapy using FSs significantly reduced the incidence of docetaxel-induced foot nail toxicity, as previously demonstrated on hands using frozen gloves.

Limitations:

  • Small sample (< 100)
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Risk of bias (sample characteristics)
  • Findings not generalizable
  • Convenience sample of consecutive patients

Nursing Implications:

Greater than half (58%) the patients were satisfied with wearing the FS, with 19% being very satisfied. This would assist nursing education for the intervention. This intervention is easy to apply with no major side effects. Because the use of FSs did not significantly affect skin toxicity, a study using a type of FS that only covers toes and nails should be tested. This intervention should also be tested with patients receiving other chemotherapy agents associated with nail and skin toxicities.

Scotté, F., Tourani, J.M., Banu, E., Peyromaure, M., Levy, E., Marsan, S., . . . Oudard, S. (2005). Multicenter study of a frozen glove to prevent docetaxel-induced onycholysis and cutaneous toxicity of the hand. Journal of Clinical Oncology, 23, 4424–4429. 

doi: 10.1200/JCO.2005.15.651
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Study Purpose:

To determine if frozen glove (FG) treatment prevents docetaxel-induced onycholysis and skin toxicity

Intervention Characteristics/Basic Study Process:

  • Patients received docetaxl 75mg/m2.
  • FG = ElastoGel (84400 APT Cedex, Akromed, France), a gel-filled sock that can supply heat or cold that was used to cover the hand to the wrist
  • The glove was refrigerated for at least three hours (–25 to –30 C), then placed on right hand for 90 minutes (intervention) 15 minutes before infusion, 1 hour of infusion, and 15 minutes after infusion. Two FGs were used sequentially to maintain a consistently low temperature.
  • The left hand was unprotected (control).
  • Onycholysis and skin toxicity were assessed at each cycle via National Cancer Institute's (NCI's) Common Terminology Criteria of Adverse Events (CTCAE) and were photo documented.

Sample Characteristics:

  • N = 45 patients
  • MEDIAN AGE = 62 years
  • AGE RANGE = 41–80 years
  • MALES: 78%, FEMALES: 22%
  • KEY DISEASE CHARACTERISTICS: Prostate cancer (58%), non-small cell lung cancer (24%), breast cancer (11%), other cancers (6%)
  • OTHER KEY SAMPLE CHARACTERISTICS: Docetaxel regimen (monotherapy, combination therapy in 58% of sample); 31% had prior chemotherapy.

Setting:

  • SITE: Multicenter    
  • SETTING TYPE: Not stated   
  • LOCATION: Paris and Poitiers

Phase of Care and Clinical Applications:

PHASE OF CARE: Active treatment

Study Design:

  • Phase-II, multicenter, matched-case controlled trial

Measurement Instruments/Methods:

  • Onycholysis/skin toxicity was assessed at each cycle by a medical investigator and repeated by another observer using NCI CTCAE, version 2. 
  • Ad-hoc rating scale: Patient global comfort assessment

Results:

  • Median number of docetaxel cycles was six
  • Median cumulative docetaxel dose was 810 mg
  • Overall occurrence of nail toxicity was lower in those with the cooling glove (11% versus 51%, p = 0.0001). None of the hands with the cooling glove developed higher than grade 1 nail toxicity. Overall skin toxicity occurred in 24% of the glove-protected hands compared to 53% of the control hands (p = 0.0001).

Conclusions:

The findings suggest that regional cooling may be of benefit to prevent nail toxicity associated with docetaxel treatment.

Limitations:

  • Small sample (< 100)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Findings not generalizable
  • Intervention expensive, impractical, or training needs
  • Questionable protocol fidelity

 

Nursing Implications:

Regional cooling may have some benefit to reduce the incidence of nail and skin toxicities associated with chemotherapy. Nurses need to be aware of patients who have cold intolerance because of peripheral neuropathies or other reasons, but this appears to be a low-risk intervention that can be helpful.

Tanyi, J.L., Smith, J.A., Ramos, L., Parker, C.L., Munsell, M.F., & Wolf, J.K. (2009). Predisposing risk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer. Gynecologic Oncology, 114, 219–224.

doi: 10.1016/j.ygyno.2009.04.007
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Study Purpose:

To evaluate the efficacy and safety profile of pegylated liposomal doxorubicin (PLD) (Doxil®) at different doses, as well as predictive factors of palmar-plantar erythrodysesthesia (PPE).

Intervention Characteristics/Basic Study Process:

The regional cooling mechanism comprised application of ice packs to the wrists and ankles during PLD administration.

Sample Characteristics:

  • The study reported on a sample of 330 women who received PLD as treatment for recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinomas.
  • Median patient age was 60 years.

Setting:

University of Texas MD Anderson Cancer Center in Houston

Study Design:

This was a retrospective chart review.

Measurement Instruments/Methods:

National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE); version not specified

Results:

  • The proportion of patients with PPE was significantly higher among those who used a cooling mechanism compared to those who did not (39% versus 26%, p = 0.0067).
  • Median overall survival and median progression-free survival did not differ between patients who received different doses of PLD.

Conclusions:

Higher doses and additional cycles of PLD were associated with a higher incidence of adverse reactions, including PPE. Potential predictors of PPE were use of cooling mechanisms, higher numbers of PLD cycles given, occurrence of mucositis, neutropenia, and peripheral neuropathy.

Limitations:

This was a retrospective study only.

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