To determine if baseline intervention in persons free of depression and anxiety can prevent development of depression or anxiety at 6 and 12 months after diagnosis

Subjects were randomized to either the immediate-intervention or delayed-intervention groups. Intervention consisted of a 90-minute face-to-face interview followed by two telephone interviews (45 minutes each) at two weeks and six weeks after the initial interview. Therapeutic intervention included storytelling about initial experiences with diagnosis, exploration of thoughts about cancer-related events and concerns, and use of a booklet for examples of ineffective coping strategies.

• At 6 months, 355 patients were evaluated for the outcome variable; at 12 months, 313 patients were evaluated for the outcome variable.
• Mean patient age was 51.4 years; age range was 18.6–70.9 years.
• Female: 321; male: 144. There were 48 men in each of the three groups. (Assignment of women and men was randomized, final sample was not described.) 
• Participants:
  • Had various cancer diagnoses.
  • Were newly diagnosed with first episode of cancer.
  • Had a judged life expectancy of at least two years.

• Single site
• Outpatient
• Manchester, Greater Manchester, England

Active treatment

Randomized controlled trial

• A concerns checklist, a 14-item checklist to measure level of concern (0–5) regarding the physical, practical, relationship, or existential aspects of cancer and its treatment. A score of 8 or above indicated risk of developing depression.
• Structured Clinical Interview for DSM-IIIR (SCID), administered by trained interviewers at 6 and 12 months.
• Hospital Anxiety and Depression Scale (HADS).

• At the 6- or 12-month follow-up, 71 patients were diagnosed with an anxiety or depression disorder. At both follow-up evaluations, 13 were diagnosed with such a disorder.
• The six-month evaluation revealed no difference between anxiety or depression development in the immediate intervention group (14.3%) and the delayed intervention group (12.3%). Therefore, the two groups were evaluated as one group in the final analysis.
• Patients in the high-risk group who received the intervention showed odds of developing anxiety or depression that were lower than those of patients in the usual-care group (p = 0.05).

The therapeutic psychological intervention demonstrated the potential to prevent disorders relating to depression and anxiety in cancer patients at high risk for development of depression.

• The study did not include an appropriate control group.
• The study confirmed inter-rater reliability of the two therapists but presented no external confirmation of the proficiency with which each adhered to the protocol.
• A large proportion of the initial sample was lost to follow-up.
• Risks of bias were due to no attentional control and an unblended design.

In-person or by-telephone cognitive behavioral intervention delivered by nurses trained in intervention delivery could help to reduce the prevalence of depression and anxiety in newly diagnosed cancer patients. Initial determination of risk for development of clinical depression and anxiety can be useful to identify those patients who may benefit most from such an intervention.

To test the hypothesis that a brief intervention would be superior to usual care to prevent anxiety or depressive disorders among newly diagnosed patients with cancer

The structured intervention was based on cognitive behavioral therapy geared toward coping and exploring beliefs and thoughts about illness. The first session was 90 minutes in person with a therapist, followed by two 45-minute sessions two and six weeks later via telephone.

• The sample was comprised of 465 patients with cancer.
• Mean patient age was 51.4 years ± 13.04.
• The sample was 69% female and 31% male.
• The most common diagnoses were breast cancer, lymphoma, and gynecologic cancers.
• Patients were excluded if they had an anxiety or depressive disorder, were taking antidepressant or anxiolytic medication, or were receiving psychological intervention.
• At baseline, 59.6% of patients were deemed to be at high risk for development of anxiety or depressive disorders.
• The majority of patients were receiving either chemotherapy or radiotherapy alone.
• Most (70%–77%) patients were married or cohabitating.

• Single site
• Outpatient setting
• Manchester, England, United Kingdom

Active treatment phase

A randomized controlled trial design was used.

• Structured clinical interview for DSM-III-R (SCII) to identify any episode of anxiety or depressive disorder
• Hospital Anxiety and Depression Scale (HADS)
• Concerns checklist: 14-item checklist of physical, practical, relationship, and existential concerns rated on a five-point scale

By the six-month time point, approximately 27% of participants were lost to follow-up or had dropped out of the study for various reasons. Those variables found to predict drop-out were age, gender, previous psychiatric history, and concerns score, some of which were the same variables reported to be predictive of developing an anxiety or depressive disorder.

At the 12-month follow-up, there was no difference between groups. In patients at high risk for developing an anxiety or depressive disorder, those in the intervention group were less likely to develop a disorder (p = 0.05). There was no difference in findings based on the timing of the intervention (immediate – within one week of starting treatment, versus delayed – eight weeks after starting treatment).

The brief intervention studied may have potential for preventing development of anxiety or depressive disorders only in those patients who were at initial high risk for development of those disorders.

• The study had no attentional control.
• The study had increased risk of bias because patients self-selected to either the intervention or control group.

To produce an evidence-based report that reviews empirical literature about depression in patients with cancer and focuses on occurrence, assessment, and treatment

Authors examined literature published January 1966–September 2000. Authors found literature by searching PubMed, PsycINFO, CINAHL, and BiOSIS Citation Index.

The most common intervention for depression is behavioral/cognitive counseling. Because hundreds of articles exist on this topic, the review was limited to several meta-analyses of psychosocial interventions; some measured emotional adjustment or distress rather than depression. All studies cited were conducted prior to 1998. Tools for measuring depression included the Hamilton Rating Scale for Depression, Clinical Global Impression, Hospital Anxiety and Depression Scale, and Montgomery-Asberg Depression Rating Scale. Descriptive reports were found on complementary treatments but no randomized controlled trials (RCTs).

Authors identified 11 RCTs of medication treatment for depression in patients with cancer. The RCTs included data about 755 patients, an average of 58 patients per study.

Some data support the efficacy of psychosocial and pharmacologic treatments for depression in people with cancer. Studies, using antidepressant medications, that conformed to usual practices for antidepressant trials did demonstrate benefit. (The studies that lasted for fewer than five weeks tended to show less benefit than did longer studies.)

RCTs of alternative or complementary interventions were not found.

To provide an evidence-based review of empiric literature, about depression in patients with cancer, that focuses on occurrence, assessment, and treatment

The search examined literature published January 1966–September 2001 and cited in PubMed, PsycINFO, CINAHL, or BIOSIS Citation Index.

Common interventions for depression are behavioral and cognitive counseling. Because hundreds of articles exist about these topics, the review was limited to several meta-analyses of psychosocial interventions. Some measured emotional adjustment or distress rather than depression. All studies cited were conducted prior to 1998. Eleven randomized, controlled trials of medication treatment for depression in patients with cancer were identified. Tools for measuring depression included the Hamilton Depression Rating Scale, Clinical Global Impression, Hospital Anxiety and Depression Scale, and Montgomery-Asberg Depression Rating Scale. Descriptive reports—but no randomized, controlled trials—were found regarding complementary treatments.

Eleven randomized, controlled trials of medication treatment for depression in patients with cancer included data from 755 patients, averaging 58 patients per study.

Some data exist regarding the efficacy of psychosocial and pharmacologic treatments for depression in people with cancer. Studies conforming to usual practices of antidepressant trials demonstrated benefit. Studies measuring at less than five weeks tended to show less benefit. Randomized, controlled trials of alternative or complementary interventions were not found.

Investigate the effect of receiving early palliative care (EPC) on changes in depression from baseline to 12 weeks and the possible impact that treatment of depression may have on survival.

For parent study patients in an outpatient thoracic oncology clinic were approached for study participation and assessed for eligibility by the clinic medical oncologists. Consented patients were randomly assigned to EPC with standard of care or standard care alone. Patients in EPC group met with a certified member of the palliative care team within 3 months of enrollment and monthly thereafter until death. The standard care group only met with palliative care upon request.

AGE  mean age 64.4 (9.6)

MALES (%) 48.3   FEMALES (%) 51.7  

KEY DISEASE CHARACTERISTICS  within 8 weeks of diagnosis with NSCLC

OTHER KEY SAMPLE CHARACTERISTICS  ECOG score of 0-2, English speaking, not already receiving palliative care
 

SITE Single site   SETTING TYPE Outpatient setting   LOCATION Massachusetts General Hospital; Boston MA
 

PHASE OF CARE End of life care

APPLICATIONS End of Life and Palliative Care
 

Secondary analysis of clinical trial data

• PHQ-9 (Depression questionnaire): Major depression syndrome (MDS) measured at baseline and 12 weeks.    
• Survival: calculated by time of enrollment until death or time of censoring data  
   

At baseline, 14% of the sample met criteria for Major Depressive Syndrome (MDS).  Median survival was shorter for patients with MDS at baseline. (5.4 months for those with MDS versus 10 months for those without MDS; p=.001). This remained after controlling for demographic variables (p=.02). PHQ-9 scores were also associated with survival, controlling for demographic factors (p<.001). Participants in the EPC group had greater improvement in PHQ-9 scores from baseline to 12 weeks compared to the standard of care group, with a mean score change of -0.96 ± 4.53 (SD). In patients with baseline MDS ( 21 patients ) those in the EPC group had greater rates of depression response at 12 weeks than the standard of care group (p=.04). Rates of new antidepressant prescriptions and mental health visits did not differ significantly between groups.

Depression is associated with survival in this sample of NSLC patients. EPC was shown to slightly improve depression score in patients with MDS scores at 3 months.

No appropriate control group

Due to the exploratory methods of the secondary analysis study causality of survival or the depression outcome cannot be inferred from the results. There is limited data to support that the intervention is associated with survival benefit related to depression.  The study was carried out at a single site which limits generalizabilty. The control group did not have any attention control intervention also limiting interpretation of study results. Impact on depression scores was only seen in 21 patients who had MDS at baseline, and the change in score was very small, with very high variability as shown by the standard deviation.  Standard care was stated to include palliative care upon patient request - the number of those who did request and also receive palliative care is not reported
 

Conclusions from this study are difficult to interpret into specific nursing intervention. Findings suggest that for those patients with a major depressive disorder, earlier and proactive involvement of a palliative care team might be of benefit in managing the depression.

To investigate the efficacy and side effects of the 186Re-hydroxyethylidene diphosphonate (HEDP) radiopharmaceutical for the treatment of pain from skeletal metastases in patients with different types of cancer

Whole-body scans and assessments were done, and patients' symptoms were evaluated to determine whether they had simple metastatic bone pain. Patients were admitted to the day-care unit and received 1,480–3,330 MBq of 186Re-HEDP in saline intravenously over 10 minutes. All patients received oral or intravenous hydration before and after infusion. Whole-body scanning was done 4–24 hours later, and external dosimetry was done at zero, one, two, four to six, and 24 hours after injection.

• N = 20  
• MEAN AGE = 55 years (range = 30–75 years)
• MALES: 40%, FEMALES: 60%
• KEY DISEASE CHARACTERISTICS: Breast, prostate, colon, renal cell, neuroendocrine, and synovial sarcoma
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were excluded if they had impending or actual fracture, impending or existing spinal cord compression, or had received hemi- or whole-body radiation in the previous three months.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Iran

• PHASE OF CARE: Late-effects and survivorship
• APPLICATIONS: Palliative care 

Phase-II observational study

• Visual Analogue Scale (VAS, 0–10)
• Dosage and type of pain medication graded from 0 (non opioids) to 3 (strong opioids) 
• Bone-scan index calculated as sum of scores of anatomic regions

The mean dose administered was 2,882 ± 675 MBq. The distribution of the tracer was seen within 4–24 hours and was correlated with the pretreatment whole-body scan. Pain relief began at around seven days after treatment. Response was observed for at least one week in 78.9% of patients and for two weeks in 63.2%. The mean duration of pain relief was 5.26 weeks (range = 1–8 weeks). There was a significant reduction of greater than three points in the first week (p = .0001) and, on average, the pain scale rating remained about 3 points below baseline at week 8 (p = .007). A transient decrease in platelets, white blood cells (WBC), and hemoglobin counts was seen. Four patients showed grade-3 platelet toxicity, 56% had at least grade-1 WBC toxicity, and 14.3% had at least a grade-2 decline in hemoglobin. A flare reaction, with a short-term worsening of bone pain, was seen in 53.5% of those who responded to the treatment and appeared to be dose-related.

186Re-HEDP may be an effective radiopharmaceutical for the palliation of metastatic bone pain.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Other limitations/explanation: The toxicity grading used was not described. Pain medications used are not described, and prior approaches in bone pain management are not described.

Pain from bone metastases is one of the most challenging areas in patients with advanced cancer. This radiopharmaceutical may provide another alternative option for pain management; however, further research is needed to determine its efficacy and toxicities and to determine the actual duration of effects. Patients receiving this agent need to be observed for bone marrow toxicities.

To identify appropriate prophylactic and therapeutic interventions for the assessment and management of skin toxicities including rash, dryness, pruritus, paronychia, hair abnormality, and mucositis in patients with cancer receiving treatment including epidermal growth factor receptor inhibitors (EGFR-Is) (e.g., cetuximab) alone or in combination with chemotherapy or radiotherapy.

In the absence of definitive evidence from clinical trials, a group of Italian expert clinicians produced recommendations for skin toxicity management in patients receiving EGFR-Is. The RAND Corporation/University of California, Los Angles (UCLA) Appropriateness Method was used for obtaining consensus on the expert opinions.

The consensus panel comprised an advisory board of nine expert clinicians from different clinical settings (six medical oncologists, two radiation oncologists, and one dermatologist). A group of 40 panelists was identified.

The database searched was MEDLINE (2005 to October 2009). Potentially relevant abstracts presented at annual meetings or gastrointestinal symposia of the American Society of Clinical Oncology and the European Society of Medical Oncology were examined.

Search keywords were EGFR inhibitors, cetuximab, skin toxicity, skin rash, and radiation dermatitis.

Studies were included in the review if they were

• In English language
• Observational, prospective studies about assessment and treatment
• Randomized, double-blind, placebo-controlled, or uncontrolled
• Retrospective and uncontrolled
• Systematic reviews and meta-analyses
• Consensus guidelines
• Reporting on available data for drugs tested in phase 3 (including abstracts).

Studies were excluded if they were published before 2005.

Patients were undergoing the active treatment phase of care.

General Prophylactic Measures Before Starting Cetuximab Treatment:

• Perform medical history and full-body skin evaluation with attention to xerosis, atopic dermatitis, and severe acne vulgaris.
• Education and general interventions may include the following.
  • Use sunscreens.
  • Avoid habits or products that can produce dry skin (e.g., hot water, alcohol-based cosmetics).
  • Enhance skin hydration (e.g., use bath oils).
  • Use alcohol-free moisturizing creams frequently.
  • Use tocopherol oil or gel.
  • Avoid tight shoes.
  • Avoid excessive beard growth, shaving with a regular shaving razor (e.g., sharp multiblade), using pre–shaving cream emollients and moisturizing aftershave, using alcohol and aftershave, or using an electric razor.

Rash

Management of Grade 1 Skin Rash (Adapted From the National Cancer Institute [NCI] Common Toxicity Criteria [CTC], Version 3):

• For skin lesions and symptoms including papules, pustules, or symptom-free erythema, do not modify cetuximab dose, interrupt treatment, or use topical or systemic treatment.
• Administer general educational and prophylactic measures.

Management of Grade 2 Skin Rash:

• Skin lesions include eruption with papules (grade 2A) or pustules (grade 2B) covering less than 50% of the body surface, with moderate symptoms and that do not interfere with daily activities.
• Do not modify cetuximab dose or interrupt treatment.
• Topical treatments include the following.
  • Antibiotics: clindamycin 1% gel, erythromycin 3% gel or cream, and metronidazole 0.75%–1% cream or gel, BID until improvement to grade 1.
  • Avoid benzoyl peroxide products.
  • Use erythromycin 2% lotion for lesions of the scalp.
• Systemic treatments include the following.
  • Prevalence of pustules (grade 2A): No systemic treatment is recommended.
  • Prevalence of pustules (grade 2B): Antibiotics include oral semisynthetic tetracyclines. Use minocycline or doxycycline 100 mg orally once per day for more than four weeks and until the rash is asymptomatic.

Management of Grade 3 Skin Rash:

• Skin lesions and symptoms include eruption with papules (grade 3A) or pustules (grade 3B) covering more than 50% of the body surface, with severe symptoms that interfere with daily activities.
• Cetuximab dose modification or treatment interruptions include the following.
  • First occurrence: Delay cetuximab infusion for less than 21 days until the skin rash improves to grade lower than 2. If the rash improves, continue at 250 mg/m². If the rash does not improve, discontinue therapy.
  • Second occurrence: Delay cetuximab infusion for less than 21 days until the skin rash improves to lower than grade 2. If the rash improves, continue at a reduced dose of 200 mg/m². If the rash does not improve, discontinue therapy.
  • Third occurrence: Delay cetuximab infusion for less than 21 days until the skin rash improves to lower than grade 2. If the rash does not improve, continue at a reduced dose of 150 mg/m². If the rash still does not improve, discontinue therapy.
  • Fourth  occurrence: Discontinue therapy definitively.    
• Topical treatment:
  • Antibiotics: Use clindamycin 1% gel, erythromycin 3% gel or cream, and metronidazole 0.75%–1% cream or gel BID until improvement to grade 1. Avoid benzoyl peroxide products. 
  • Use erythromycin 2% lotion for lesions of the scalp.
• Systemic treatment:
  • Antibiotics include oral semisynthetic tetracyclines. Use minocycline or doxycycline 100 mg orally once per day for more than four weeks and until the rash is asymptomatic.
  • Corticosteroids: Use methylprednisolone 0.4 mg/kg orally or prednisone 0.5 mg/kg orally for up to 10 days.
• Systemic treatment for grade 3, highly symptomatic or nonresponsive patients:
  • Retinoids: isotretinoin 0.3–0.5 mg/kg orally
  • Corticosteroids: methylprednisolone or dexamethasone via IV
  • Antihistamines: clorfenamine intramuscularly (IM) or via IV
  • Antibiotics: amoxicillin or clavulanic acid and gentamicin via IV

Management of Grade 4 Skin Rash:

• Skin lesions include generalized rash with severe symptoms that require emergency treatment.
• Discontinue therapy immediately and definitively.
• Topical treatment:
  • Antibiotics: Use clindamycin 1% gel, erythromycin 3% gel or cream, and metronidazole 0.75%–1% cream or gel BID until improvement to grade 1. Avoid benzoyl peroxide products.
  • Use erythromycin 2% lotion for lesions of the scalp.
• Systemic treatment:
  • Retinoids:  isotretinoin 0.3–0.5 mg/kg orally
  • Corticosteroids:  methylprednisolone or dexamethasone via IV
  • Antihistamines: chlorpheniramine IM or via IV
  • Antibiotics: amoxicillin or clavulanic acid and gentamicin via IV
  • Hydration via IV
  • Hospitalization

Xerosis, Fissures, and Eczema

Prevention:

• General educational and prophylactic measures are important.
• Regular use of emollient ointments, almond oil, and preparation of polyethylene glycol is recommended.

Management:

• For eczema, use topical treatment with medium-potency corticosteroids for one to two weeks.
  • Betamethasone dipropionate 0.05%–0.1% cream
  • Clobetasone 0.05% cream
  • Ointment fluocinolone acetonide
  • Hydrocortisone butyrate 0.1% cream
  • Consider simple or occlusive dressing for the extremities.
  • Topical antibiotic is recommended for superinfection.
    • Fusidic acid 2% cream
    • Bacitracin cream
    • Mupirocin 2% cream

Paronychia

Prevention:

• Avoid friction and pressure on the nail fold (e.g., avoid tight shoes).

Management:

• Wash with antiseptics including diluted hydrochloric acids solution or boric acid solution 3%.
• Use creams containing corticosteroids and antiseptics.
  • Betamethasone 0.05% plus clioquinol 3% ointment
  • Betamethasone 0.1% plus gentamicin 0.05% cream
  • Betamethasone 0.1% plus gentamicin 0.1% cream
  • Betamethasone valerate 0.1% plus fusidic acid 2% cream
  • Triamcinolone acetonide 3% plus chlortetracycline 0.1% ointment
  • Triamcinolone benetonide 2% plus fusidic acid 0.03% cream
• Use oral antibiotics for superinfection.
  • Amoxicillin or clavulanic tablets
  • Cefalexin tablets
  • Clindamycin capsules
• Use analgesic drugs (nonsteroidal anti-inflammatory drugs) orally.

The use of cetuximab in treating colorectal and head and neck cancer has significantly affected patient outcomes. A strategic approach to managing skin toxicities that includes consensus recommendations from experts will guide clinicians in minimizing the incidence of skin rash, improve compliance, and optimize patient outcomes.

Nurses who will be managing grade 1 and 2 skin toxicities should receive education. In addition, use of a multidisciplinary approach when managing skin rashes is paramount. Facilities may choose to create algorithms as an effective strategy to establish consistent processes for the assessment and management of skin toxicities induced by EGFR-I therapy.

The purpose of this meta-analysis and systematic review was to obtain pooled estimates of comparative efficacy of pegfilgrastim and filgrastim.

The PubMed and EMBASE databases were used.

Key words were neupogen, filgrastim, recombinant methionyl human granulocyte–colony-stimulating factor, G-CSF, CSF, longrastim, polyethylene glycol conjugated filgrastim and related terms

Studies were included if they were randomized, controlled trials (RCTs) if the patients were adults with non-myeoloid cancer, had a test of a single 6 mg dose or 100 mcg/ke of pegfilgrastim after start of chemotherapy, and a daily filgrastim comparator. Endpoints included grade 4 neutropenia, febrile neutropenia, and time to ANC recovery.

94 total references were retrieved.

• Five studies were included in the final analysis.
• The sample consisted of 617 patients, and size range across the five studies was 27–296.
• Key characteristics were breast cancer,  lymphoma, and non-Hodgkin lymphoma.

Active anti-tumor treatment

Standard mean difference (SMD) for time to ANC recovery showed mixed results across studies and pooled SMD to time to recovery was not statistically significant. There was no significant difference between drugs in rates of bone pain. Multiple different grouping and analyses of data were done to try to show differentiation of effect and when meta-analysis was limited to two phase III trials. Relative risk (RR) for febrile neutropenia for pegfilgrastim relative to filgrastim was 0.56 (95% CI [0.35, 0.89], p < 0.016).  Rates for neutropenia were not different.

Results suggest that daily filgrastim and single-dose pegfilgrastim provide essentially the same effect for time to ANC recovery, grade 4 neutropenia rates, and bone pain.

Some studies had very small samples, and heterogeneity with all studies was significant. Studies involved the use of different chemotherapy regimens which could have influenced findings here.

Both pegfilgrastim and filgrastim appear to provide similar clinical effects for prevention of neutropenia and febrile neutropenia. The side effect of bone pain was similar with both treatments. Pegfilgrastim dosing requires fewer subcutaneous injections.

To test the hypothesis that a home-based exercise intervention would improve fitness and physical activity and to determine the intervention effects on fatigue, self-reported physical functioning, and quality of life (QOL).

Those randomized to the exercise program received in-person instructions on how to exercise at a moderate intensity level, monitoring heart rate and how to warm-up and cool-down with exercise. Patients in the exercise group were asked to keep activity logs and were encouraged to exercise at least 10 minutes two days per week, increasing to 30 minutes per day, at least five days per week. Each received a weekly telephone call for the 12-week study to identify problems and reinforce participation, using cognitive-behavioral processes of change tailored to each patient. Patients in the control condition received weekly calls for 12 weeks for the administration of a symptom questionnaire and problem monitoring. Patients then received monthly telephone calls for three months. Telephone calls were audiotaped, and 25% of the tapes were reviewed for content to ensure fidelity to the study protocol. Study measures were obtained at baseline and at 3, 6, and 12 months.

• The sample was comprised of 46 patients (56.5% female, 43.5% male). 
• Mean age was 55.6 years (standard deviation [SD] = 8.24 years) in the control group and 59.5 years (SD = 11.2 years) in the exercise group. 
• All patients had colorectal cancer, with an average of three years since diagnosis.
• All patients had undergone surgery, and most did not receive radiation or chemotherapy treatment. 
• A majority of the patients had attended college and had a median income of greater than $60,000.

• Single site
• Home
• Rhode Island

Patients were undergoing multiple phases of care.

The study was a randomized, controlled trial.

• Seven-day Physical Activity Recall (7-day PAR)
• Treadwalk maximal fitness test
• Community Health Activities Model Program for Seniors (CHAMPS) questionnaire
• Functional Assessment of Cancer Therapy–Fatigue and Colorectal subscales (FACT-F and FACT-C)
• Short Form 36 (SF-36) physical functioning subscale

Both groups showed improvement in fitness and physical functioning over time, as well as increased physical activity. The exercise group showed a greater increase in physical activity at three months, but there was no difference from the control group at 6 or 12 months. During the first three months, the exercise group also showed significant improvement from baseline in CHAMPS energy expenditure and motivational readiness; however, these effects declined after three months. The intervention group demonstrated better submaximal aerobic fitness than the control group at all time points (p < 0.02). There were no significant intervention effects on fatigue, physical functioning, or QOL. These outcomes improved in all patients, and these improvements were sustained throughout the 12 months of follow-up. The authors speculated that the lack of apparent impact on fatigue may be associated with the fact that patients were highly functioning, although their baseline fatigue levels were lower than those seen in other studies in which exercise was effective.

The home-based exercise program improved patients’ physical activity, motivation, and fitness; however, it did not demonstrate an impact on fatigue or QOL. Activity and motivation were most improved during the first three months, when they received weekly telephone calls, suggesting that frequent contact may have been important in these results.

• The study had a small sample size, wth less than 100 patients.
• No information was provided regarding patient adherence to the recommended exercise program from patient logs.
• The lack of differences in CHAMPS between groups suggests that their actual activity levels were not substantially different.
• The majority of patients were highly educated and in a higher socioeconomic status and almost 100% were white, suggesting that these findings may not be applicable to other types of patients.

The findings suggest that a home-based exercise program can improve physical activity and aerobic fitness, but it did not appear that these improvements translated into reduced fatigue. Further research in the area of exercise and fatigue are needed to determine if exercise may be most effective in patients with greater fatigue at baseline.

To determine the efficacy of topical vitamin K1 as prophylaxis for cetuximab-induced skin rash (CISR) in patients with metastatic colorectal cancer

• N = 41
• MEAN AGE =  67.2 years (SD = 8.2 years)
• MALES: 25 (61%), FEMALES: 16 (39%)
• KEY DISEASE CHARACTERISTICS: Metastatic colorectal cancer (mCRC)
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were receiving cetuximab with or without chemotherapy. 61% of patients had a single metastatic site (mostly in the liver). Cetuximab was the first- or second-line treatment in nearly 73% of patients mainly in association with irinotecan; only one patient had a relevant skin comorbidity (e.g., previous temporal herpes zoster). 

• SITE: Single-site  
• SETTING TYPE: Outpatient  
• LOCATION: Turin, Italy

• PHASE OF CARE: Active antitumor treatment

Prospective, single cohort study design

• The investigators collected demographic data, the degree of disease extension, and occurrence and assessment data regarding the degree of cetuximab-induced skin reactions (CISR) including rash, xerosis, paronychia, and nail and hair changes.
• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI, CTCAE) v3.0

Overall, 34 patients (82.9%) experienced CISR of any grade. During the first eight weeks of treatment, the grade and incidence of patients’ skin toxicity was grade 0 (6 patients, 15%); grade 1 (18 patients, 45%); grade 2 (10 patients, 25%); and grade 3 (6 patients, 15%). No grade 4 CISR was reported. The mean time to development of the maximum grade of rash was 34.7 days, and the median time was 28 days (SD = 24.7). All patients with grades 2–3 rashes were managed with topical or systemic antibiotics. Dermatologic consultation was provided to all six patients with grade 3 rash.

Overall, this study found that patients with mCRC who were treated with cetuximab and used vitamin K1-based cream prophylactically experienced a lower proportion of grade 2 rash (25%) and grade 3 rash (15%), which corresponds to the lower limit reported in the literature. Also, patients tolerated this treatment well.

• 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
• Other limitations/explanation: Study involved only one disease type: mCRC. Forty-one consecutive patients were enrolled. No control.

The topical application of vitamin K1-based cream may reduce the risk of developing skin rashes to the lower limits of rash reported elsewhere in the literature. Prophylactic use of vitamin K1 cream is tolerated well by patients receiving cetuximab therapy.