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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. 

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.

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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. 

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.

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Scott, A. (2014). Polymeric membrane dressings for radiotherapy-induced skin damage. British Journal of Nursing, 23, S24–S31.

Study Purpose

To determine whether a polymeric membrane dressing is effective for radiation skin reactions in patients who scored between 1-2.5 on the Radiation Treatment Oncology Group's (RTOG's) acute radiation morbidity scoring criteria over a four-week period

Intervention Characteristics/Basic Study Process

All patients were provided with aqueous cream to use at the start of treatment prior to application of the Polymem® polymeric dressing. They were also provided with paraffin gauze for moist desquamation. It was unclear when the patients started using Polymem and paraffin gauze. An evaluation form was developed to capture baseline details and weekly assessments for up to four weeks including “patient’s age, gender, radiotherapy dosage, nutritional status, cancer type and location, RTOG rating, wound size, location, and description, wound-pain score, and pain at dressing change.” In addition, dressing wear time, prescribed analgesia, and healing rates were documented. Part of the intervention included patient diaries that captured a daily record of wound-pain scores using the Wong and Baker FACES® scale, a log of whether the pain was related to cancer or dressing change, pain medications, sleep patterns, and free text. It did not report randomization. The four particular performance criteria that were assessed were improving skin integrity, managing dry and moist desquamation, relieving pain and inflammation, and improving quality of life (sleep patterns). Patients and clinicians rated dressing satisfaction and performance.

Sample Characteristics

  • N = 20
  • MEAN AGE = 56.8 years
  • MALES: 17 (85%), FEMALES: 3 (15%)
  • KEY DISEASE CHARACTERISTICS: Primary diagnosis was head and neck cancer
  • OTHER KEY SAMPLE CHARACTERISTICS: 30% were diagnosed with squamous cell carcinoma of the larynx

Setting

  • SITE: Single-site (assumed, not clearly described)
  • SETTING TYPE: Cancer center
  • LOCATION: Mount Vernon Cancer Centre, Middlesex, United Kingdom

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active treatment

Study Design

Observational, quasiexperimental trial

Measurement Instruments/Methods

  • RTOG Morbidity Scoring Scale
  • Wong and Baker FACES® Scale
  • Malnutrition Universal Screening Tool (MUST)
  • World Health Organization's (WHO's) Analgesic Ladder

Results

Sixteen (80%) patients applied either aqueous cream or paraffin gauze prior to applying Polymem dressing.
  • 13 (65%) RTOG = 2
  • 5 (25%) RTOG = 2.5
  • 2 (10%) RTOG = 1
  • 0 (0%) RTOG = 3 or 4
Improving skin integrity
  • Patient response and clinical observation: Within the first week of treatment, skin reactions were reduced in both dry and moist desquamation.
  • First week: Eight patients healed.
  • Second week: Five patients healed.
  • Third week: Two patients healed but stopped using dressing.
  • Fourth week: Two patients were healing but had not completely healed.
  • 15% of patients' skin reactions healed.
Managing dry and moist desquamation
  • Patient response and clinical observation: Within the first week of treatment, skin reactions were reduced in both dry and moist desquamation.
Relieving pain and inflammation
  • Through days 1 to 14, pain levels declined with mean self-reported pain scores being 6–7 (day 1) and 1–2 (day 14)
  • During the first 14 days, patients took a combination of codeine, co-codamol, and paracetamol.
  • Patients reported a significant reduction in wound pain and increased comfort with dressings usage.
Improving quality of life (sleep patterns)
  • No patients were taking sedative medications or practicing relaxation techniques. By the sixth day, patients that kept pain diaries reported sleeping four to eight hours out of a 24 hour day.
  • Journal diaries reported increased sleeping hours.
Patients and clinicians rated dressing satisfaction and performance.
  • Journal diaries reported that patients and their caregivers were able to change the dressings.

Conclusions

In this setting, because of the results of this small study, Polymem dressings have replaced paraffin gauze and aqueous creams for patients with head and neck cancer. Polymem dressings reduced pain and inflammation, improved sleep patterns, and improved healing rates and quality of life. However, there were many limitations.

Limitations

  • Small sample (< 30)
  • Baseline sample/group differences of import
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Risk of bias (no appropriate attentional control condition)
  • Selective outcomes reporting
  • Measurement/methods not well described
  • Measurement validity/reliability questionable
  • Findings not generalizable
  • Intervention expensive, impractical, or training needs
  • Other limitations/explanation: Patients and clinicians should have been trained in assessment as there may have been discordance in reporting. This method was not clearly described.
 

 

Nursing Implications

Polymeric dressings may reduce the severity of radiodermatitis, promote healing, and reduce associated pain. This report had numerous limitations and does not provide strong evidence for the efficacy of these dressings. Additional, well designed research is warranted.

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Scott, D.A., Mills, M., Black, A., Cantwell, M., Campbell, A., Cardwell, C.R., . . . Donnelly, M. (2013). Multidimensional rehabilitation programmes for adult cancer survivors. The Cochrane Database of Systematic Reviews, 3, CD007730. 

Purpose

STUDY PURPOSE: To conduct a systematic review of studies examining the impact of multidimensional rehab programs

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: MEDLINE, EMBASE, CINAHL through February 2012, Cochrane Register of Controlled Trials (CENTRAL)

KEYWORDS: Extensive listing of search terms per database is provided.

INCLUSION CRITERIA: RCT or quasi RCT, interventions included a physical and psychological component, sample is adults who have completed cancer treatment, at least two treatments of the intervention were provided

EXCLUSION CRITERIA: Not specified

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 25,824

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Used a checklist of study characteristics for risk of bias. Nine studies had insufficient information to evaluate risk of bias.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 12 (6 studies that used the SF36 for outcome measures were included in meta-analysis)
  • SAMPLE RANGE ACROSS STUDIES: 24–543
  • TOTAL PATIENTS INCLUDED IN REVIEW = 1,669
  • KEY SAMPLE CHARACTERISTICS: Prostate and breast cancer were most prevalent patient types. One study involved head and neck, and four studies included multiple cancer types.

Results

Two studies showed no benefit of the intervention, seven showed benefit in one domain, and three reported significant improvement in physical and psychosocial domains. Three studies specifically reported fatigue outcomes with combinations of CBT or psychoeducational and exercise interventions. All of these had moderate-to-high risk of bias. Duration of interventions that was longer than 12 weeks showed no additional improvement over interventions delivered up to 12 weeks. Interventions delivered face-to-face appeared to be more effective, and additional telephone follow-up “boosters\" improved results. Meta-analysis of physical and mental components of SF36 measures showed no statistically significant overall effect of the intervention. The nature, timing, and duration of interventions varied substantially across studies.

Conclusions

There is insufficient evidence to assess the efficacy of multidimensional rehab programs to improve fatigue in individuals with cancer. Programs with a single focus may be more successful in improving outcomes that are the focus of the intervention. Face-to-face delivery with follow-up boosters appear to be most effective.  Beneficial effects seen appear to plateau after about six months.

Limitations

Meta-analysis was possible on only a few studies. Few studies used objective measures of physical component outcomes. Program adherence by patients was not often reported in studies.

Nursing Implications

Findings here do not show sufficient evidence to fully evaluate the effectiveness of multidimensional rehab programs to improve fatigue or physical and psychological outcomes for cancer survivors. Such programs may have short-term benefit for some patients, and it appears that interventions delivered face-to-face with follow-up may be more effective.

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Scope, A., Lieb, J.A., Dusza, S.W., Phelan, D.L., Myskowski, P.L., Saltz, L., & Halpern, A.C. (2009). A prospective randomized trial of topical pimecrolimus for cetuximab-associated acnelike eruption. Journal of the American Academy of Dermatology, 61, 614–620.

Study Purpose

To determine the ability of topical pimecrolimus to reduce the severity of cetuximab-related facial rash.

Intervention Characteristics/Basic Study Process

Patients aged 18 years or older with metastatic colorectal cancer who were on cetuximab treatment and experienced a rash were eligible for randomization. Open-label pimecrolimus 1% cream was to be applied to one side of the face BID for five weeks. Patients completed a daily dairy. Physicians queried patients about side effects and compliance during study visits. Complete skin examinations were performed by dermatologists who were blinded to study applications. Digital photos were used for review. Patients were asked about the presence and perceived severity of rash-associated symptoms on either side of the face. Counts of facial lesions on both sides of the face were performed by blinded dermatologists at weeks 2, 5, and 7. The study took place over five weeks.

Sample Characteristics

  • The study reported on a sample of 16 patients with metastatic colorectal cancer.
  • Patients were aged 18 years or older.
  • Gender was not reported.

Setting

  • Single site
  • Outpatient
  • New York City Hospital in New York

Phase of Care and Clinical Applications

Patients were undergoing the active treatment phase of care.

Study Design

This was a single-blind, randomized, prospective clinical trial, with patients used as their own controls.

Measurement Instruments/Methods

  • Baseline evaluation    
  • Skin assessment by dermatology
  • Digital photography of faces
  • Clinical and skin assessment at weeks 2, 5, and 7
  • Counts of facial lesions at weeks 2, 5, and 7
  • Patient-completed daily study diary

Results

  • A statistically significantly greater decrease in lesion counts existed for the treatment versus observational sides of patients' faces by week 2. This result was maintained by week 5, but was nonsignificant after stopping cream by week 7.
  • No significant differences existed in rash severity.
  • No difference existed in the frequency of patient-assessed itch, burning, and dryness or perceived degree of facial erythema between treated and untreated sides of the face, per patients’ report.
  • Of note, a bilateral decrease in rash severity was reported at week 7.

Conclusions

Pimecrolimus application did not translate into clinically significant benefit in patients with cetuximab-related facial rash.

Limitations

  • The sample size was small (fewer than 30 patients).
  • The study was not placebo controlled.

Nursing Implications

Rash may improve without interventions.

Print

Scope, A., Agero, A.L., Dusza, S.W., Myskowski, P.L., Lieb, J.A., Saltz, L., . . . Halpern, A.C. (2007). Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. Journal of Clinical Oncology, 25, 5390–5396.

Study Purpose

To compare the effectiveness of placebo versus minocycline 100 mg every day for eight weeks, beginning on day 1 of cetuximab infusion, to prevent or reduce cetuximab-induced rash in patients with metastatic colorectal cancer.

To compare the effectiveness of receiving tazarotene cream BID for eight weeks on one side of the patient’s face versus not receiving the topical treatment on the other side of the patient’s face.

Intervention Characteristics/Basic Study Process

Twenty-four patients were randomized to the oral minocycline (100 mg per day) arm, and 24 patients were randomized to the oral placebo arm. Treatment was administered starting on day 1 of cetuximab therapy and continued for eight weeks.

All patients received open-label, topical tazarotene 0.05% cream (Tazorac®) application to one side of their face, starting on day 1 of cetuximab therapy and continuing for eight weeks.

Sample Characteristics

  • The study reported on a sample of 48 adult men and women with stage IV metastatic colorectal cancer, who were preparing to initiate treatment with cetuximab.
  • Mean patient age was 61 years (range 39–83 years).

Setting

  • Single center
  • Memorial Sloan-Kettering Cancer Center

Study Design

This was a randomized, double-blind, placebo-controlled trial.

Measurement Instruments/Methods

Follow-up clinical assessment was completed at weeks 1, 2, 4, and 8, with questionnaires and skin examination, including skin lesion counts and digital photos.

Results

  • Initially, 48 patients were randomized in this study. At the end of the eight-week trial, 35 patients were included in the final analysis (18 patients in the minocycline arm and 17 patients in the placebo arm).
  • A significant overall difference existed in log lesion counts between the minocycline arm (fewer lesions) and the placebo arm (p = 0.005). The difference was apparent by week 1, peaked at weeks 2 and 4, and tapered by the end of the study (week 8).
  • At week 4, a decreased proportion of patients in the minocycline arm reported moderate-severe itch compared to those in the placebo arm.
  • Patients in the minocycline arm trended toward decreased frequency of moderate-severe rash compared to those in the placebo arm. Those differences diminished by week 8.
  • In four patients in the placebo arm (8%), cetuximab treatment was interrupted because of grade 3 dermatologic adverse events. Cetuximab treatment was not interrupted for any patients in the minocycline arm.
  • Topical treatment with tazarotene did not translate into a meaningful clinical benefit.
  • Of the 43 patients available for at least one clinical evaluation, 14 (33%) discontinued tazarotene prematurely as a result of local irritation.
  • Three additional patients (7%) reported stopping tazarotene after one month because of subjective lack of efficacy compared to the control side of the face.
  • In a review of facial photography at week 4 (n = 39), no difference existed in rash severity between the tazarotene and observation sides of the face (n = 34, 87%), and the rash was assessed as more severe in four patients (10%) who received tazarotene.

Conclusions

Prophylactic treatment with minocycline appears to significantly decrease the severity of acneform rash during the first eight weeks of cetuximab therapy. Continuation of this therapy beyond eight weeks is not beneficial.

Results suggest that topical tazarotene has no role in the management of cetuximab-induced rash.

Limitations

  • The sample size was small (48 at the start of the study; reduced to 35 by the end of eight weeks).
  • The measurement tool or method used to grade rash symptoms was not described.
  • A combination of interventions was used; therefore, determining the effectiveness of the individual interventions is difficult.
Print

Scope, A., Agero, A.L., Dusza, S.W., Myskowski, P.L., Lieb, J.A., Saltz, L., . . . Halpern, A.C. (2007). Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. Journal of Clinical Oncology, 25, 5390–5396.

Study Purpose

To compare the effectiveness of placebo versus minocycline 100 mg every day for eight weeks, beginning on day 1 of cetuximab infusion, to prevent or reduce cetuximab-induced rash in patients with metastatic colorectal cancer.

To compare the effectiveness of receiving tazarotene cream BID for eight weeks on one side of the patient’s face versus not receiving the topical treatment on the other side of the patient’s face.

Intervention Characteristics/Basic Study Process

Twenty-four patients were randomized to the oral minocycline (100 mg per day) arm, and 24 patients were randomized to the oral placebo arm. Treatment was administered starting on day 1 of cetuximab therapy and continued for eight weeks.

All patients received open-label, topical tazarotene 0.05% cream (Tazorac®) application to one side of their face, starting on day 1 of cetuximab therapy and continuing for eight weeks.

Sample Characteristics

  • The study reported on a sample of 48 adult men and women with stage IV metastatic colorectal cancer, who were preparing to initiate treatment with cetuximab.
  • Mean patient age was 61 years (range 39–83 years).

Setting

  • Single center
  • Memorial Sloan-Kettering Cancer Center

Study Design

This was a randomized, double-blind, placebo-controlled trial.

Measurement Instruments/Methods

Follow-up clinical assessment was completed at weeks 1, 2, 4, and 8, with questionnaires and skin examination, including skin lesion counts and digital photos.

Results

  • Initially, 48 patients were randomized in this study. At the end of the eight-week trial, 35 patients were included in the final analysis (18 patients in the minocycline arm and 17 patients in the placebo arm).
  • A significant overall difference existed in log lesion counts between the minocycline arm (fewer lesions) and the placebo arm (p = 0.005). The difference was apparent by week 1, peaked at weeks 2 and 4, and tapered by the end of the study (week 8).
  • At week 4, a decreased proportion of patients in the minocycline arm reported moderate-severe itch compared to those in the placebo arm.
  • Patients in the minocycline arm trended toward decreased frequency of moderate-severe rash compared to those in the placebo arm. Those differences diminished by week 8.
  • In four patients in the placebo arm (8%), cetuximab treatment was interrupted because of grade 3 dermatologic adverse events. Cetuximab treatment was not interrupted for any patients in the minocycline arm.
  • Topical treatment with tazarotene did not translate into a meaningful clinical benefit.
  • Of the 43 patients available for at least one clinical evaluation, 14 (33%) discontinued tazarotene prematurely as a result of local irritation.
  • Three additional patients (7%) reported stopping tazarotene after one month because of subjective lack of efficacy compared to the control side of the face.
  • In a review of facial photography at week 4 (n = 39), no difference existed in rash severity between the tazarotene and observation sides of the face (n = 34, 87%), and the rash was assessed as more severe in four patients (10%) who received tazarotene.

Conclusions

Prophylactic treatment with minocycline appears to significantly decrease the severity of acneform rash during the first eight weeks of cetuximab therapy. Continuation of this therapy beyond eight weeks is not beneficial.

Results suggest that topical tazarotene has no role in the management of cetuximab-induced rash.

Limitations

  • The sample size was small (48 at the start of the study; reduced to 35 by the end of eight weeks).
  • The measurement tool or method used to grade rash symptoms was not described.
  • A combination of interventions was used; therefore, determining the effectiveness of the individual interventions is difficult.
Print

Science, M., Robinson, P.D., MacDonald, T., Rassekh, S.R., Dupuis, L.L., & Sung, L. (2014). Guideline for primary antifungal prophylaxis for pediatric patients with cancer or hematopoietic stem cell transplant recipients. Pediatric Blood and Cancer, 61, 393–400.

Purpose & Patient Population

PURPOSE: To provide healthcare providers with evidence-based recommendations on the use of primary antifungal prophylaxis in children with cancer and undergoing hematopoietic stem cell transplantation (HSCT)

TYPES OF PATIENTS ADDRESSED: Allogeneic and autologous HSCT recipients, children with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), and pediatric patients with anticipated neutropenia for longer than seven days

Type of Resource/Evidence-Based Process

RESOURCE TYPE: Evidence-based guideline 

PROCESS OF DEVELOPMENT: Literature search was done, and included studies were evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system. Recommendations were established by a panel discussion. Guidelines then were externally reviewed by another interprofessional expert panel and provided to Canadian pediatric tertiary hospitals for stakeholder review.

DATABASES USED: MEDLINE, EMBASE, Cochrane Collaboration, proceedings of the American Society of Clinical Oncology and American Society of Hematology    

KEYWORDS: Not stated

INCLUSION CRITERIA: RCTs involving patients of any age with cancer or undergoing HSCT that compared antifungal agents with another antifungal agent, placebo, or no prophylaxis; no language exclusions

EXCLUSION CRITERIA: Trials involving nonsystemic antifungal treatment

Phase of Care and Clinical Applications

  • PHASE OF CARE: Multiple phases of care            
  • APPLICATIONS: Pediatrics

Results Provided in the Reference

Initially, 7,869 references were retrieved and screened. A final set of 47 studies were included.

Guidelines & Recommendations

The following are strong recommendations.

  • Children one month to 19 years undergoing allogeneic HSCT should have fluconazole daily from the start of conditioning until engraftment (high-quality evidence).
  • When fluconazole is contraindicated, echinocandin should be used as an alternative (moderate-quality evidence).
  • Children undergoing autologous HSCT with anticipated neutropenia for longer than seven days should receive fluconazole daily from the start of conditioning until engraftment (moderate-quality evidence).
  • Children with AML or MDS should receive fluconazole daily during chemotherapy-associated neutropenia (moderate-quality evidence).

Additional weak recommendations also are outlined in the guidelines.

Limitations

Although these guidelines are aimed at pediatric patients, 17 studies included did not include children in the sample.

Nursing Implications

These evidence-based guidelines clearly recommend primary antifungal prophylaxis in at-risk children. Specific dosages recommended are identified in this reference.

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Schwartzberg, L., Jackson, J., Jain, G., Balu, S., & Buchner, D. (2011). Impact of 5-HT(3) RA selection within triple antiemetic regimens on uncontrolled highly emetogenic chemotherapy-induced nausea/vomiting. Expert Review of Pharmacoeconomics & Outcomes Research, 11(4), 481–488.

Study Purpose

To assess the likelihood of uncontrolled chemotherapy-induced nausea and vomiting (CINV) events following antiemetic prophylaxis with the 5-HT3 receptor antagonist (RA) palonosetron plus aprepitant or fosaprepitant and dexamethasone versus any of the other 5-HT3 RAs (granisetron, dolesetron, ondansetron) plus aprepitant or fosaprepitant and dexamethasone among single-day, highly emetogneic chemotherapy (HEC) cycles

Intervention Characteristics/Basic Study Process

This was a retrospective analysis of a healthcare claims database from January 2006 through June 2010 using data from International Classification of Diseases book 9 (ICD-9), Current Procedural Terminology (CPT), and pharmacy claims. Investigators evaluated two cohorts. The palonosetron cohort consisted of patients initiating antiemetic prophylaxis with palonosetron plus aprepitant or fosaprepitant and dexamethasone. The \"other 5-HT3 cohort\" consisted of patients receiving any other 5-HT3 RA plus aprepitant or fosaprepitant and dexamethasone.

Sample Characteristics

  • In all, 4,552 patients met the selection criteria; 3,574 for the palonosetron cohort and 978 for the other 5-HT3 cohort. Mean age was 53 years.
  • The sample was 23% male and 77% female.
  • To be included in the study, patients could be diagnosed with any cancer but must have received treatment with a single-day, HEC regimen (defined as chemotherapy administrations with at least a 5-day gap between two consecutive administrations). Breast cancer was the predominant malignancy (n = 2,313, approximately 50%) followed by “multiple cancers” (n = 1,282, approximately 30%). All HEC-treated patients were required to have received a prophylactic antiemetic regimen that included a 5-HT3 plus dexamethasone plus fosaprepitant or aprepitant regimen.
  • In the database, the payer-type distribution was 80% commercial, 15% other, 3% Medicaid, and 1.7% Medicare Risk. All patients included in the database were eligible for medical and pharmacy benefits.

Phase of Care and Clinical Applications

Patients were undergoing the active treatment phase of care.

Study Design

This was a retrospective data analysis.

Measurement Instruments/Methods

CINV was defined as at least one of the following during days 2–5 post chemotherapy: a diagnosis of nausea or vomiting (ICD-9 code); hydration procedure (CPT code); rescue medication use of any of the following: dexamethasone, diphenhydramine, olanzapine, promethazine, haloperidol, prochlorperazine, lorazepam, or metoclopramide; or antiemetic administration of palonosetron, ondansetron, granisetron, dolasetron and fosaprepitant/aprepitant by oral or IV routes.

Results

A total of 8,018 cycles for the palonosetron cohort and 1,926 cycles for the other 5-HT3-RA cohort were analyzed. Single-day HEC cycles received by the palonosetron cohort had a significantly lower unadjusted risk of an uncontrolled CINV event with a 17% lower risk for palonosetron-administered cycles versus 21% risk for other 5-HT3 RAs (p = 0.0010). Results in the breast cancer and multiple cancer subgroups were consistent with those for the overall population.

Conclusions

This study suggests that all 5-HT3 RAs may not be equivalent in preventing delayed CINV for patients receiving single-day HEC; however, the study design limits the strength of the evidence.  

Limitations

  • No appropriate control group was included.
  • The study is limited in its design because retrospective database analysis does not allow for assessment of potential differences between cohorts in terms of patient history of CINV-predictive factors such as alcohol use and motion sickness.
  • The study does not evaluate multiple-day regimens of HEC. 
  • The data were taken from claims with the assumption that patients billed for antiemetic medications, prescriptions, or hydration experienced an “uncontrolled CINV event” and patients that did not have this same associated claim data did not have an uncontrolled CINV event. However, this does not reflect the practice styles of prescribers or patient reports. Some prescribers routinely give patients oral rescue antiemetic prescriptions and have them filled prior to the start of treatment. Additionally, patients may have had unreported or untreated CINV or may have taken prophylactic treatment without actually experiencing uncontrolled CINV. 
     

Nursing Implications

Nurses may want to consider substituting palonosetron as 5-HT3 in antiemetic regimen for single day HEC.

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Schwartzberg, L., Morrow, G., Balu, S., Craver, C., Gayle, J., & Cox, D. (2011). Chemotherapy-induced nausea and vomiting and antiemetic prophylaxis with palonosetron versus other 5-HT(3) receptor antagonists in patients with cancer treated with low emetogenic chemotherapy in a hospital outpatient setting in the United States. Current Medical Research and Opinion, 27(8), 1613–1622.

Study Purpose

To compare the incidence of chemotherapy-induced nausea and vomiting (CINV) among patients with cancer receiving low emetogenic chemotherapy (LEC) when given an antiemetic prophylaxis treatment of palonosetron versus other 5-HT3 receptor antagonists. 

Intervention Characteristics/Basic Study Process

Using the Premier Perspective database, medical records were reviewed to identify patients with cancer who began LEC between the dates of 4/1/2007 and 3/31/2009. The medical records were then examined to determine the type of prophylactic antiemetic therapy prescribed and the patients were divided into two groups: patients prescribed palonosetron and patients prescribed other 5-HT3 receptor antagonists (ondansetron, granisetron, or dolasetron). For the time period encompassing either the first eight cycles of chemotherapy or the first six months of treatment (whichever occurred first), the medical records were examined to determine the rate of acute and delayed CINV events, CINV-related rescue medications used, and CINV-related admissions that occurred during the study follow-up period. Acute events were defined as occurring on day one of a chemotherapy cycle, and delayed events were defined as occurring on days two through seven of a chemotherapy cycle. Outcomes were compared for those patients who were prescribed palonosetron as antiemetic prophylaxis versus those who were prescribed other 5-HT3 receptor antagonists as antiemetic prophylaxis.

Sample Characteristics

A total of 2,439 patients were included in the study.

Mean age was 66.3 years (SD = 12.6 years).

The sample was 54.2% male and 45.8% female.

Cancer diagnoses were lung, gynecological, head and neck, noncolon gastrointestinal, breast, urinary tract, and other or unknown.

All patients were beginning LEC and receiving palonosetron or other 5-HT3 receptor antagonists as antiemetic prophylaxis.

Setting

This was a multisite, inpatient and outpatient review of data from more than 600 hospitals from across the United States.

Phase of Care and Clinical Applications

Patients were undergoing the active treatment phase of care.

Study Design

This was a nonexperimental, retrospective, longitudinal, observational study.

Measurement Instruments/Methods

  • Medical records were reviewed to identify any documented events of emesis, nausea, or volume depletion that occurred.
  • Medical records were reviewed to identify any documented rescue medications used to treat established nausea or emesis.
  • Medical records were reviewed to identify any documented hospitalizations due to nausea, emesis, volume depletion, dehydration, or hypovolemia.

Results

Patients receiving palonosetron experienced significantly fewer CINV events (nausea, vomiting, volume depletion) (p < 0.0001), used significantly fewer antiemetic rescue medications (p < 0.0001), and were emergently/urgently admitted to the hospital significantly fewer times (p < 0.0001) than patients taking other 5-HT3 antagonists.

Conclusions

Among patients with cancer receiving LEC, palonosetron may offer more relief from CINV compared to that offered by older-generation 5-HT3 antagonists.

Limitations

This was a retrospective study that compared palonosetron against a pool of other 5-HT3 antagonists, with no random assignment to antiemetic medication. This makes it difficult to attribute the study results to the effects of the target “intervention” (palonosetron) and not to other factors.

Nursing Implications

Palonosetron is a newer 5-HT3 antagonist with different receptor-binding characteristics and a longer half-life than older-generation 5-HT3 antagonists. It may offer more relief from the effects of CINV compared to standard prophylactic emetic therapy. However, one important issue that was noted was that, with LEC, delayed nausea and vomiting was more of an issue than acute. Current guidelines suggest antiemetics that address only nausea and vomiting that occur in the acute phase. Palonosetron could replace older generation 5-HT3 antagonists as standard prophylactic antiemetic therapy, but more research is needed.

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