To treat breast cancer-related lymphedema based on clinical audit results

Clinical audit of effective and ineffective treatment programs Inform the decision-making process regarding focus of care and funding efforts. The study surveyed three years of treatment data on onset and duration of swelling, severity (size and extent), lymphedema treatment received, and changes in severity over time. of 2,486 treatment sessions, 65% (1608) were manual lymph drainage (MLD) optimal intensive offered to all with moderate to severe lymphedema. Only 19 patients were willing to commit to the program. This was followed by MLD and compression garments. All patients with moderate to severe lymphedema were taught daily skin care, exercise, 

• Of the patients at London Haven, 268 patients were eligible.
• Patients were excluded if they had advanced disease or bilateral lymphedema.
• Ninety-five patients declined treatment.
• The sample was comprised of 168 patients.
• Seventy-four (44%) had follow-up data for 12 months for analysis.

The study took place at London Haven.

• Severity of swelling at first presentation measured by perometer excess limb volume (percentage excess limb volume [ELV])
• ELV mild swelling was less than 20%, ELV moderate 20%-40%, and ELV severe more than 40%.
• Breast and trunk swelling clinically determined by observation and palpation and patient report. 

Of patients with mild, uncomplicated lymphedema, 75% (39/52) received standard self-care regimen of hosiery, exercise, and skin care. Those patients had a mean reduction of 30% ELV was achieved by 13 patients for whom 12-month data were available. Thirteen (25%) received a short course of MLD (six sessions over two weeks). Mean reduction was 20% ELV, which is less than that achieved by self-care measures alone. Some patients in self-care group had stopped wearing their hosiery because at three and six months they had such improvement. Thirty-nine patients presented with breast or trunk edema and were treated with MLD and also taught self-massage. Of the 20 patients for whom 12-month data were available, 14 had complete resolution of edema. Moderate-to-severe lymphedema Intensive therapy was offered to 77 patients. Only 19 (25%) underwent one or more courses of intensive therapy. Twelve-month data was available on only 16 patients. At 12 months, swelling had reduced by 40% and six patients had little or no remaining edema. For those patients unable to do intensive therapy, mean reduction was 25%.

Breast edema treatment showed most improvement with MLD, self-care

• The results are based on cohort, observational data.
• The study only reflects the experience of one institution. 
• Costs of intensive therapy in terms of time, finances, and access were not fully addressed.

The audit reinforced the need for programs to offer full-service intensive therapy for patients with moderate to severe lymphedema. For patients unable or unwilling to commit to multilayer bandaging, MLD and self-care hosiery provided 25% reduction in ELV and warrants further investigation. Early treatment is advocated because almost 60% of patients developed symptoms within the first year postsurgery; only half had sought assistance from a lymphedema specialist within three months of onset of symptoms.

• FINAL NUMBER STUDIES INCLUDED = 2 
• TOTAL PATIENTS INCLUDED IN REVIEW = 22
• KEY SAMPLE CHARACTERISTICS: Various types of cancer, primarily lung cancer; study 1 age range was 63–80 years, study 2 mean age was 66 years

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

In the two studies included in this review, neither study showed any benefit to nebulized furosemide for dyspnea when compared to controls. Both studies used different doses of nebulized furosemide. Neither study reported adverse effects.

Nebulized furosemide was not beneficial for the relief of dyspnea in patients with cancer.

• Only included two studies
• Sample size was extremely small
• Measured outcomes varied significantly between studies
• Different doses of nebulized furosemide were used in each study
• High attrition rates in included studies
• Difficulty recruiting reported for included studies

Many patients with cancer experience feelings of dyspnea. Nurses should assess patients for the underlying causes of dyspnea and use appropriate interventions to treat these causes. In both intervention studies and in systematic reviews, nebulized furosemide has not been shown to be beneficial for patients with cancer who experience dyspnea.

To examine the effect of modafinil on patient-reported fatigue in patients with cancer who were undergoing chemotherapy.

Assessments were conducted at baseline after randomization and shortly after cycle two of therapy. Modafinil or placebo was started at 100 mg on day 10 or day five of study cycle two, then increased to a full dose of 200 mg after three days. This regimen then was continued until day seven of treatment cycle four, at which time all patients discontinued medication.

• A total of 877 participants were enrolled, and 631 were analyzed.
• Mean ages for the study groups were 60 and 61 years (range 18–90), and 66% to 68% were female.
• The most common sites were gastrointestinal, breast, and lung. The sample also included genitourinary, gynecologic, hematologic, and other cancers.
• Participants were required to be beginning a cancer treatment course of at least four planned cycles of chemotherapy with at least two weeks apart, with no concurrent radiation or interferon treatment.
• Patients were excluded if they had taken modafinil or any psychostimulant within the past 30 days.
• Participants had at least a score of 2 on the Brief Fatigue Inventory (BFI) question 3 (worst level of fatigue).
• Of the patients, 57% had received prior chemotherapy, and 22% to 24% had received prior radiation therapy.
• Most (67%–70%) participants were married, and about half had some college education.

This multisite study was set in 23 geographical areas across the United States among University of Rochester Cancer Center Community Clinical Oncology Program (URCC CCOP) affiliates.

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

• BFI, question 3
• Epworth Sleepiness Scale (ESS) to measure excessive daytime sleepiness
• Profile of Mood States depression subscale (POMS-DD)
• Missing scores at cycle four were replaced with scores from cycle three for those who completed the study and only had evaluable data through cycle three (n = 58 for modafinil; n = 29 for placebo).

ANCOVA for BFI fatigue score showed an interaction between treatment effects and baseline BFI score (p = 0.017). A significant difference existed between the study groups for those who had severe fatigue at baseline (BFI of 7 or greater), with average score in the modafinil group. No differences in fatigue were observed between the study groups for those who had mild or moderate baseline fatigue. Daytime sleepiness on ESS showed significant improvement in the modafinil group (p = 0.002). No significant differences existed in depression outcomes between the groups. In the modafinil group, 11% of patients experienced adverse events, and in the placebo group, 9% had adverse events. Only three adverse events were judged to be definitely associated with treatment with modafinil: allergic reaction, dyspnea, and headaches.

The findings supported the use of 200 mg of modafinil as an effective treatment for severe cancer-related fatigue in patients undergoing chemotherapy. Modfinil was not effective for patients with less severe fatigue.

• It is not clear what the statistical effect was of the replacement of missing cycle four data with data from cycle three. The authors analyzed multiple data replacements to test this and found no differences. This suggests that the time frames of the study measures were irrelevant.
• The study demonstrated effectiveness for the short term during active treatment with only chemotherapy; the findings may not be the same for other groups of patients or other time frames of observation.
• Diversity of the sample in terms of racial and some other demographic findings was limited.
• Although no significant differences existed between study groups that would have affected the study results, the findings may not be applicable to other patients with different demographic characteristics.

To evaluate the effect of honey and 0.15% benzydamine hydrochloride on the onset and severity of radiation mucositis when compared to 0.9% normal saline

• Patients in group I were instructed to rinse their mouths and swish 20 mL of honey for 5 minutes and slowly swallow. This was to be done 15 minutes before, 15 minutes during, and 6 hours following radiation therapy (RT).
• Group II was instructed to rinse and then spit with 15 mL of 0.15% benzydamine hydrochloride for 5 minutes. This was to be done 15 minutes before, 15 minutes during, and 6 hours following RT.
• Group III (control group) was instructed to rinse with 20 mL of 0.9% normal saline for five minutes and then spit. This was to be done 15 minutes before, 15 minutes during, and 6 hours following RT.  
• The clinical grading of mucositis followed the World Health Organization (WHO) mucositis grading scale on day 1 of RT, daily during treatment, and weekly for two weeks following completion of RT.

• The study reported on 60 patients with an age range of 49–55 years.
• The sample was 70% male and 30% female.
• All patients had oral malignancies and were being treated with RT.

This was a single site, outpatient study conducted in Chennai, India.

Patients were undergoing the active antitumor treatment phase of care.

 This was a three-group, randomized, controlled trial.

Patients were assess via clinical exam.

The onset of mucositis and progression to grades 2, 3, and 4 were noted for each group. Group I had a later onset of grades 1, 2, 3, and 4 mucositis compared to Groups II and III. The difference was statistically significant (p < 0.001).

Honey can be an effective agent in managing radiation-induced oral mucositis. It is simple, inexpensive, and readily available. Further randomized studies are essential to validate the findings.

• The sample size was small with fewer than 100 patients.
• A risk of bias exists because of the lack of blinding.
• A risk of bias exists because of the variations in sample characteristics. For example, the duration of RT varied from 6000-7000 centiGray, and this variation was explained by time not the total dose. The authors did not describe if this difference between groups was statistically significant.
• Although the authors acknowledged that the intensity of mucositis can be altered by fractionation schedules, concurrent chemoradiotherapy, and comorbid medical conditions, including bacterial colonization of the oral mucosa, the study did not address these variables.
• The authors did not discuss how well the patients tolerated the honey.
• Subject withdrawal was not addressed. 
• Pain measurement was not addressed.

Mucositis during RT for oral malignancy is a continuing challenge for patients. Further testing of honey is needed. The availability and cost are benefits. The treatment is not complex or impractical.

To attempt to confirm the benefit of the antibiotic tetracycline in decreasing the severity of epidermal growth factor receptor (EGFR)–inhibitor-induced rash.

Eligible patients who were starting an EGFR inhibitor and were rash free were randomly assigned to tetracycline 500 mg orally BID for 28 days, versus placebo. Rash development and severity, quality of life, and adverse events were monitored during the four-week intervention and for an additional four weeks. The primary objective was to compare the incidence of grade 2 or worse rash between the study arms.

• The study reported on a sample of 65 patients aged 18 years or older.
• The sample was 63% male and 36% female.
• All patients had a cancer diagnosis and were starting an EGFR inhibitor.

Patients were undergoing the active treatment phase of care.

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

• Patients were monitored for rash severity by physician report using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.   
• Patient-reported questionnaire regarding rash
• Patient-reported quality of life as per the Skindex-16 questionnaire
• Patient-reported series of linear analogue self-assessment (LASA) scales
• Adverse events reported by the patient and physician
• Patient diary regarding compliance with EGFR inhibitor consumption

• The cumulative incidence of grade 2 or worse rash was comparable across study arms.
• Quality of life also was not significantly different between study arms.

This randomized, double-blinded, placebo-controlled study did not find that tetracycline decreased rash incidence or severity in patients who were taking EGFR inhibitors.

The sample size was small (fewer than 100 patients).

Quality of life was comparable and tetracycline was well tolerated, but the current results did not support what prior studies had suggested.

To compare the effectiveness of tetracycline 500 mg orally BID versus placebo for 28 days starting on day 1 of treatment with any epidermal growth factor receptor–inhibitor (EGFRI) agent to prevent or reduce EGFRI-induced rash in patients with cancer.

Patients were randomized to either the tetracycline arm (500 mg orally BID for 28 days) or the placebo arm.

• The study reported on a sample of 61 adult men and women with cancer.
• Thirty-one patients were randomized to the tetracycline arm, and 30 patients were randomized to the placebo arm.
• Median patient age was 71 years in the tetracycline arm and 63 years in the placebo arm.

This study was a collaborative effort of the North Central Cancer Treatment Group (including centers in Illinois, Iowa, Kansas, South Dakota, and Ohio) and the Mayo Clinic (Rochester, MN).

This was a placebo-controlled, doubled-blind trial.

Three patient-reported assessments were used.

• A brief rash incidence questionnaire
• SKINDEX-16 questionnaire relevant to rash development and its implications on patients' quality of life (this tool was previously validated)
• Questionnaire regarding patient compliance with EGFRI therapy

Those three questionnaires were completed at baseline and weekly for eight weeks after initiation of tetracycline or placebo. Oncologists performed an evaluation at the end of four weeks and eight weeks. The evaluation included a history and physical examination, an assessment of patient performance status, and an assessment of adverse events (e.g., gastrointestinal toxicity, rash development) as per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.

• At week 4, 70% of patients in the tetracycline arm (n = 16) and 76% of patients in the placebo arm (n = 22) developed a rash (p = 0.61).
• At week 8, 87% of patients in the tetracycline arm (n = 13) and 84% of patients in the placebo arm (n = 16) developed a rash (p = 0.84).
• By week 4, physician-reported grade 2 rash or rash covering more than 50% of body surface area (BSA) occurred in 17% of patients in the tetracycline arm (n = 4) and 55% of patients in the placebo arm (n = 16) (p = 0.04).
• By week 8, when 44% of the cohort had dropped out, physician-reported grade 2 rash or rash covering more than 50% of BSA occurred in 27% of patients in the tetracycline arm (n = 4) and 47% of patients in the placebo arm (n = 9) (p = 0.5).
• Of note, the worst physician reported rash (grade 3) occurred in one patient in the tetracycline arm.
• Results of the SKINDEX-16 questionnaire did not demonstrate uniform, statistically significant differences, with a few exceptions. Tetracycline exerted positive effects on quality of life in four questions (skin itching, skin burning or stinging, skin irritation, and being bothered by a persistence or recurrence of the skin condition). Tetracycline exerted a negative effect on one question (bothered about being annoyed about your skin). No statistical significance was found for the remaining 11 questions.
• Tetracycline was well tolerated with no significant difference in adverse events between study arms.

Administration of tetracycline prophylactically did not significantly affect the incidence of rash development in patients receiving EGFRI drugs. Indicators suggest administration of tetracycline prophylactically may have a favorable influence with regard to rash severity in patients receiving EGFRI drugs. In addition, the results suggested these rashes bother patients, who must contend with itching, burning, and other types of skin irritation.

• The sample size was relatively small.
• The measurement method for clinician grading of rash symptoms was not described.
• Six patients, including three patients from each study arm, stopped taking EGFRI medication within the first month because of the development of skin rash.

The study was conducted to test oral donepezil and oral vitamin E in patients with small-cell lung cancer after completion of all cancer therapy and prophylactic cranial irradiation.

A randomization procedure was conducted after participant stratification in the following ways.

• Baseline cognitive function on the Mini-Mental State Examination (MMSE) placed participants in three impairment groups: normal, mild to moderate, and severe.  
• Participants were categorized by age into two groups, 60 years or younger or older than 60 years.

The treatment group received 5 mg/day of oral donepezil, which increased to 10 mg/day after one month of therapy if tolerated well. Treatment group participants also received 1000 IU/day of oral vitamin E. The control group was given an identical oral placebo. Assessments were performed at study enrollment, one month, and every three months until cancer recurrence or treatment failure.

• The total number of participants enrolled over 15 months was 9.
• There were 4 participants in the treatment group and 5 participants in the control group.  
• All participants had a diagnosis of small-cell lung cancer.
• All participants had a limited disease status and similar prophylatic carnial irradiation.  
• All participants had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2.
• The mean age of the treatment group was 67, with a range of 65–69.
• The mean age of the control group mean was 67, with a range of 60–76.
• The treatment group was 100% male; the control group was 80% male and 20% female.

The study took place at the North Central Cancer Treatment Group and the Mayo Clinic.

The study was a double-blind, placebo-controlled trial.

• The Mini-Mental State Examination (MMSE) was used to measure global cognitive functioning. A three-point drop indicated treatment failure.
• A five-point drop on the Blessed Dementia Scale indicated treatment failure.
• The Common Terminology Criteria for Adverse Version 2.0 was also used. 

There were no notable differences in cognitive stability, adverse events, or quality of life between treatment arms. Only one patient, who received donepezil and vitamin E, manifested a three-point drop in cognitive scores as measured by the MMSE. There was a slight trend of increased gastrointestinal side effects among patients treated with donepezil and vitamin E.

The median time spent in the study was 42 or 69 days for the treatment or control group, respectively.

Due to low enrollment and retention, the effect of oral doses of vitamin E and donepezil on cognitive function could not be determined. 

• The study had a small sample size.
• Inclusion criteria seriously limited eligibility and enrollment.
• Participant withdrawal tended to occur sooner in the study for those receiving the medication intervention than among those in the control group. No explanation for subject withdrawals was provided.

To evaluate the efficacy of megestrol acetate versus dronabinol, as well as a combination of these treatments

This was a randomized, controlled, three-arm trial using a double-blind procedure. The first arm evaluated the efficacy of 800 mg/day of oral megestrol acetate plus a capsule placebo; the second arm evaluated the efficacy of 2.5 mg of oral dronabinol twice daily plus a liquid placebo; and the third arm combined both medications. Evaluations were taken at noted doses.

The final sample included 469 patients. The sample was stratified for confounding factors, including age, gender, cancer type, estimate of survival, performance status, severity of weight loss, concomitant radiation therapy, treatment center, and planned or ongoing treatment. Sample size calculations included a power analysis and accounted for attrition.

All participants shared the following characteristics:

• Adults with an incurable malignancy, with the exception of brain, breast, ovarian, and endometrial cancers 
• An estimated life expectancy of three months or more, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 
• A self-reported weight loss of at least five pounds and/or physician-estimated caloric intake of 20 or fewer calories/kg of body weight/day.

North Central Cancer Treatment Group (NCCTG) trial involving 20 NCCTG institutions, including the Mayo Clinic

A double-blind, randomized controlled trial design was used.

• Weight was measured using home scales and office scales.
• Anorexia was assessed using validated NCCTG questionnaires.
• Quality of life was assessed using a single-item Uniscale and a 13-item, anorexia-specific Functional Assessment of Anorexia/Cachexia Cancer Therapy (FAACT) instrument. The validity and reliability of these instruments was previously reported.

No differences between groups at baseline were noted. A greater percentage of patients treated with megestrol acetate reported appetite improvement (75% versus 49%; p = 0.0001) and baseline weight gain (11% versus 3%, p = 0.02) for ≥ 10%) compared with dronabinol-treated patients. Combination treatment conferred no additional benefit.

FAACT demonstrated improved quality of life among megestrol acetate–treated and combination-treated patients. Uniscale scores were similar for both groups. Toxicity among groups was comparable, with the exception of a greater incidence of impotence among men who received megestrol acetate.

• The study lacked a constitutive definition of anorexia.
• Eligibility criteria used self-reported weight loss and physician estimates of caloric intake.
• Outcome measures used weight measurement in the oncologist’s office; accuracy and precision of the scale used to assess weight were not explicated.
• Validity and reliability of instruments was not included.
• Recruitment sites were listed, but these settings were not described.
• Cost implications were not discussed.

To evaluate the efficacy of ecosapentaenoic acid (EPA) supplement plus placebo versus megestrol acetate plus placebo supplement versus combination of both EPA supplement and megestrol

The EPA dose was 1.09 g BID in supplement plus liquid placebo. The megesterol acetate dose was 600 mg/day plus placebo supplement BID. The combination dose was EPA 1.09 g supplement BID plus megesterol acetate 600 mg/day. Patients were stratified and randomized to one of three treatment arms. Median number of days on study was relatively equal for all three arms at slightly more than three months. Megesterol acetate served as the control arm secondary to its proven efficacy.

• The study reported on 421 patients.
• Inclusion was based on age 18 years or older with incurable malignancy other than brain, breast, ovarian, prostate, or endometrial cancer; life expectancy of three months or more; Eastern Cooperative Oncology Group performance status of 2 or better; and self-reported two-month weight loss of five or more pounds and/or physician-estimated daily intake of less than 20 calories/kg/day.
• All patients had to perceive that weight loss was a problem, and the physicians had to view weight gain as a beneficial outcome.
• Exclusion criteria other than previously listed tumor types were use of tube feedings or parenteral nutrition; edema or ascites; use of adrenal steroids (other than short-term dexamethasone with chemotherapy), androgens, progestational agents, or other appetite stimulants within the past month; brain metastases; insulin-requiring diabetes; pregnancy; lactation; poorly controlled hypertension or congestive heart failure; history of thromboembolism; and obstruction in alimentary tract, malabsorption, or intractable vomiting.

The study was a collaborative effort of the North Central Cancer Treatment Group (NCCTG) and the National Cancer Institute of Canada, conducted at 26 primary treatment centers.

A double-blinded, randomized, three-armed trial design was used.

• Weight measured at MD’s office at baseline and monthly
• NCCTG questionnaire to measure appetite and weight loss at baseline, weekly, for four weeks, and then monthly 
• Functional Assessment of Anorexia/Cachexia Therapy (FAACT) administered at same intervals as above
• Single-item uniscale question to measure global quality of life administered at same intervals as above

The primary endpoint was weight gain of 10% or more (chosen because of previously proven efficacy of megesterol acetate). Among the three arms, 6% of patients achieved this in the EPA arm, 18% in the megesterol arm, and 11% in the combination arm. There was a p value of 0.01 showing greater efficacy with single-agent megesterol acetate. Appetite results using the NCCTG questionnaire were comparable for all three groups, showing varying degrees of favorable effects in all treatment arms. Appetite results using FAACT showed that the megesterol acetate and combination arms provided better appetite stimulation than EPA alone: 40 for EPA, 55 for megesterol acetate, and 55 for combination.

There was no significant difference for survival times or quality of life between the three arms. Recommendation of authors is not to use EPA alone or in combination.

Sample size was very good, and statistical analysis was very thorough.

• The study did not include a true placebo arm; therefore, the orexigenic effects of EPA cannot be determined but rather only suggested since there was an equivalent result on the NCCTG questionnaire when compared to megesterol acetate.
• No definition of anorexia was provided.

To determine whether sunscreen prevents or mitigates epidermal growth factor receptor–inhibitor (EGFRI)-induced rashes.

Patients were stratified based on (a) first-line cancer therapy versus other therapy, (b) type of EGFRI prescribed or anticipated (e.g., small molecule inhibitor versus monoclonal antibody), and (c) use of a concurrent medication that increases sun hypersensitivity.   

Patients were randomly assigned to sunscreen with a sun protection factor (SPF) of 60 to be applied to the face, trunk, and extremities BID for 28 days versus an identical-appearing  placebo. The sunscreen included 7.5% titanium dioxide and 7.5% zinc oxide, and was shown to block more than 90% of both ultraviolet A and ultraviolet B light in preclinical trials. All patients were instructed to stay indoors or in a covered area from 10 AM to 3 PM to avoid peak sun exposure. 

• The study reported on a final sample of 89 patients. Initially, 54 patients were in the sunscreen arm and 56 patients were in the placebo arm.
• Median patient age was 63 years (range 36–90) in the sunscreen arm and 62 years (range 37–88) in the placebo arm.
• The sample was 54% female and 46% male in the sunscreen arm, and 52% female and 48% male in the placebo arm.
• In the sunscreen arm, 22 patients (41%) had lung cancer, 22 patients (41%) had gastrointestinal cancer, and 10 patients (19%) had another type of cancer. In the placebo arm, 17 patients (30%) had lung cancer, 23 patients (41%) had gastrointestinal cancer, and 16 patients (29%) had another type of cancer.
• EGFRI characteristics were as follows. In the sunscreen arm, 21 patients (39%) received erlotinib (or another small molecule inhibitor) and 33 patients (61%) received cetuximab (or another antibody). In the placebo arm, 22 patients (39%) received erlotinib (or another small molecule inhibitor), and 34 patients (61%) received cetuximab (or another antibody).

• Multi-site
• Outpatient clinic
• United States

Patients were undergoing the active treatment phase of care.

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

• History and physical (baseline, end of week 4, and end of week 8)
• Performance status score (baseline, end of week 4, and end of week 8)
• Brief rash incidence questionnaire (weekly for eight weeks)
• Skindex-16 (quality-of-life tool) (weekly for eight weeks)
• Previously used questionnaire on patient compliance with EGFRI therapy (weekly for eight weeks)
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (end of week 4 and end of week 8)

• During the four-week intervention, physician-reported rash occurred in 38  patients (78%) in the sunscreen arm and 39 patients (80%) in the placebo arm (p = 1.00). No statistically or clinically significant differences existed in physician-reported rash severity or patient-reported outcomes of rash. Adjustments for sun intensity by geographical zone, season, and use of photosensitivity medication did not yield a significant difference in rash across the study arms (p = 0.2). 
• The patient-reported Skindex-16 questionnaire did not reveal major differences between the study arms. Quality-of-life scores declined but remained comparable between arms. 
• The sunscreen was well tolerated with low and almost identical rates of adverse events in the two study arms.
   

The use of sunscreen (SPF of 60) did not prevent or decrease the severity of EGFRI-induced rash.

• The sample size was fewer than 100 patients. 
• No tool was available to measure the actual degree of sun exposure for each patient.  
• The generalizability of the results is limited. This study primarily included patients who were receiving erlotinib or cetuximab. Other small molecule inhibitors (e.g., lapatinib) and monoclonal antibodies (e.g., panitumumab) exist, and patients receiving those drugs might respond to sunscreen differently.
• Patients were not to be in the sun from 10 AM to 3 PM, so their sun exposure was greatly limited. In addition, actual patient compliance with avoidance of sun exposure and application of sunscreen or placebo was not evaluated or reported.

No evidence existed to support the use of sunscreen to prevent or decrease the severity of EGFRI-induced rash.