To evaluate the effects of a stellate ganglion block (SGB) and steroids on breast cancer-related lymphedema

Patients were randomly assigned to one of three groups using different substances injected for SGB, (1) bupivacaine alone, (2) bupivacaine and triamcinolone, or (3) triamcinolone alone. Patients were given three consecutive blocks every two weeks. Outcome measurements were obtained at two, four, and eight weeks.

• N = 32  
• MEAN AGE = 54.7 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer, and all but one received surgery with lymph node dissection

• SITE: Single site  
• SETTING TYPE: Outpatient    
• LOCATION: South Korea

• PHASE OF CARE: Transition phase after active treatment

Double-blinded, randomized, controlled study

• Forearm and upper arm circumference measurement
• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30)

Forearm circumference was significantly decreased in all groups one month after three treatments. Upper arm measures showed significant reductions at different time points across the three groups, but all showed a statistically significant reduction over time (p < 0.017). Those who received SGB with triamcinolone had a slightly larger reduction in upper arm circumference. There were no differences between groups in quality of life measures.

SGBs may be a viable alternative treatment for breast cancer-related arm lymphedema. The use of a corticosteroid for the block might produce the most effective results.

• Small sample (< 100)

SGBs may be an effective alternative treatment for breast cancer-related lymphedema. Additional research is needed to confirm these findings.

To demonstrate that DA-3031 is not inferior to daily filgrastim to manage neutropenia

Patients were randomly assigned to receive daily filgrastim or DA-3031. Daily filgrastim at 100mcg/m² began 24 hours after chemotherapy was started and continued until absolute neutrophil count was at least 5 x 10⁹, or for 10 days. Those in the experimental group received 6 mg DA-3031 by subcutaneous injection on day 2 of each chemotherapy cycle. Patients received TAC chemotherapy every three weeks up to six cycles. The noninferiority margin set was two days for the duration of grade 4 neutropenia.

• N = 74 for ITT analysis, 63 completed the protocol
• MEAN AGE = 6.44
• AGE RANGE = 30–67 years
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had breast cancer and were receiving TAC chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: Previous colony-stimulating factor exposure, prior hematopoietic cell transplantation, and prior treatment with antibiotics within 72 hours of starting chemotherapy were exclusions.

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Korea

PHASE OF CARE: Active antitumor treatment

Open-label, noninferiority, randomized, controlled trial

• Common Terminology Criteria for Adverse Events, version 4
• Time to absolute neutrophil count recovery to at least 2 x 10⁹/L

Mean duration of grade 4 neutropenia was 2.08 (SD = 0.85) days for the filgrastim group and 2.28 (SD = 1.14) days for the DA-3031 group. The difference between groups was 0.2 (SD = 1) days, supporting noninferiority of DA-3031. There were no significant differences between groups in absolute neutrophil coutn recovery time, incidence of febrile neutropenia, hospitalization, or requirement for intravenous antibiotics. There was no significant difference between groups in musculoskeletal symptoms associated with colony-stimulating factor administration. The findings were similar across all chemotherapy cycles. ITT and per protocol analysis were similar.

DA-3031, a once-per-cycle colony-stimulating factor, was not inferior to daily filgrastim.

• Small sample (< 100)
• Risk of bias (no blinding)
• ITT analysis had a 90% power.

DA-3031, a pegylated colony-stimulating factor was comparable to daily pegfilgrastim for neutropenia-related outcomes among women receiving TAC therapy. A once-per-cycle colony-stimulating factor can be more practical for patients because it does not require daily injections. Comparative costs of these two approaches was not discussed and may need to be considered in the selection of an approach.

To evaluate the safety and efficacy of once-per-cycle DA-3031 in patients receiving chemotherapy for breast cancer

Patients were randomized to daily injections of filgrastim 100 mcg/m² beginning 24 hours after chemotherapy until absolute neutrophil count (ANC) was 5x10⁹ after nadir or up to 10 days, or to one of two doses of pegfilgrastim (3.6 mg or 6 mg). The primary endpoint was duration of grade 4 neutropenia.

• N = 61
• MEAN AGE = 44.9 years
• AGE RANGE = 29–67 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer and were receiving chemotherapy consisting of doxorubicin, cyclophosphamide, and docetaxel. Chemotherapy was given every three weeks for up to six cycles.

• SITE: Multi-site 
• SETTING TYPE: Outpatient 
• LOCATION: South Korea

• PHASE OF CARE: Active antitumor treatment

• Randomized, open-label, phase II

• National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.01)

No significant differences were seen among groups in ANC nadirs or time to recovery. Overall incidence of febrile neutropenia was 9.8%, with no significant differences between groups. The most common adverse event was musculoskeletal pain, with no significant differences between groups, although pain was slightly higher in the 6 mg pegfilgrastim group.

Single-dose pegfilgrastim had similar efficacy and side effects to daily filgrastim.

• Small sample (less than 100)
• Risk of bias (no blinding)

Daily dosing of filgrastim had essentially the same efficacy and side effects as once-per-cycle pegfilgrastim. Severity of musculoskeletal pain appeared to be slightly higher with the higher dose of pegfilgrastim. Reducing the need for daily injections may be an important consideration for some patients and has been shown to have essentially the same effects. Higher doses may be associated with increased musculoskeletal pain. Although not statistically significant, this can be an important consideration to promote patient quality of care.

Primary Aim:  To evaluate the effectiveness of author-defined intensive use (three times daily [TID] use starting two or three weeks before radiotherapy [RT] and continuing this frequency throughout RT) application of a lotion preparation made of 3% urea, polidocanol, and hyaluronic acid for preventing the appearance of acute radiodermatitis and controlling its severity in patients actively undergoing RT for breast cancer.

Secondary Aim:  To study effectiveness, the authors compared the incidence and grade of toxicity with 174 patients with breast cancer treated in the same clinic the previous year. These patients used skin-support measures at the beginning of RT or when radiodermatitis occurred.

Ureadin cream was used TID for two to three weeks prior to the start of external beam RT (EBRT) and continued for the entire treatment period. This use was considered intensive compared to other studies and the standard use schedule of twice daily (BID) cream application at the start of RT or 10 days before starting RT.

• The sample was comprised of 98 women with breast cancer.
• Mean age was 59 years (range 57–61).
• Patients were treated with conservative surgery and scheduled to start EBRT with a 10-week follow-up period. 
• The RT field included the entire mammary gland; maximum dose was 50 Gy in 25 fractions of 2 Gy each day, followed by an electron boost to the surgical bed to a total dose 60 to 70 Gy.
• One patient had RT to the internal mammary lymph nodes.
• RT was interrupted in two patients; one was due to grade 3 radiodermatitis (14-day interruption) and one required vertebroplasty (40-day interruption).

• Single site  
• Outpatient
• Radiation Oncology Department, Hospital General de Catlunya, Spain

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for late effects and survivorship.

This was a prospective, observational study performed over 14 months.

• Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) acute toxicity scale:  weekly evaluation
• Visual analog scale (VAS) for patients to rate pain, itching, redness, desquamation, and effect on quality of life (QOL)
• Numeric scale (0–3) for patients and physicians to rate effectiveness, tolerability, and cosmetic properties of the lotion (0 = poor; 1 = moderate; 2 = good; 3 = excellent). Also, patients were asked to give an overall score out of 10.

The overall rate of radiodermatitis was 72.4%, with 51% of patients being toxicity grade 1; 20% grade 2, and 1% grade 3. The first case of skin toxicity appeared in third week of treatment; in >87% of patients, radiodermatitis appeared between weeks 5 and 7. The severity of radiodermatitis with the intensive use of the lotion was significantly lower (72.4% vs. 84.5%; p < 0.05). The grade of toxicity was significantly lower in intensive-use patients (p < 0.001), and grade 2 toxicity or higher was significantly lower (21.4% vs. 50%; p < 0.01). Severity of clinical symptoms of pain, itching, redness, desquamation, and impact on QOL was reported as negligible by patients.

For patients with breast cancer who undergo conservative surgery and will receive RT to a dose of 60 to 70 Gy, use of Ureadin on an intensive basis (TID beginning two to three weeks prior to the start of RT) compared to BID use is considered effective at reducing the incidence and grade of skin toxicity during RT and is well tolerated by patients.

•  The study had a small sample size, with less than 100 patients.
•  The study lacked an appropriate control group.

1. Intensive use of skin care preparation two to three weeks prior to starting RT seems effective at reducing the incidence of skin toxicity and probably increases better tolerance to RT for patients with breast cancer.
2. The ingredients in this lotion (urea, hyaluronic acid, and polidocanol) seem effective in keeping irradiated skin hydrated and lessening reports of pain, redness, and itching experienced by patients undergoing EBRT to the breast.
3. It is possible that these findings could be useful for other cancer diagnoses for patients undergoing EBRT.
4. The cost burden to patients would need to be studied; if patients are starting a prophylactic skin care regimen two to three weeks before RT, during the six to seven weeks of RT, and for one to two weeks after RT, is it cost-effective to prescribe this regimen routinely? (Online search of amazon.com showed Ureadin-Iralfaris-lotion supplied as 250 mL for $30.95).
5. Depending on the type of cancer, date of simulation, and start date for RT, it may not be feasible to start this skin care regimen two to three weeks prior to start of RT.
6. It would be interesting to compare the effectiveness of Ureadin to US commercial preparations containing hyaluronic acid (i.e., XClair, Miaderm, or Biafine).

• FINAL NUMBER STUDIES INCLUDED = 11 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,091 
• KEY SAMPLE CHARACTERISTICS: Women who received either modified radical mastectomies or breast conservation surgery along with different axillary node management

PHASE OF CARE: Late effects and survivorship
 
APPLICATIONS: Elder care

Weight training exercise with low to moderate intensity (no trials used high-intensity weight training) and relatively slow progression significantly improved upper limb strength (SMD = 0.93, 95% CI 0.73–1.12) and lower limb strength (SMD = 0.75, 95% CI 0.47–1.04) without increasing arm volume or the incidence of breast cancer-related lymphedema. No significant effects were noted for body mass index (SMD = -0.10, 95% -0.31–0.11). Some aspects of quality of life may have improved with weight training. Participants in all trials used pressure garments and received supervision.

Weight training appeared to be safe and beneficial in improving limb strength and the physical components of quality of life in women with or at risk of lymphedema. Pressure garments, supervision, and limiting the intensity of the weight training may be important, but this could not be confirmed with this review.

A potential selection bias of the studies reviewed may exist because no blinding methods were employed among authors and affiliations. Heterogeneity among the studies reviewed limited the scope of the statistical analysis, so a narrative synthesis and meta-analysis were conducted. Heterogeneity may also limit the generalizability of the overall study results.

This review indicated that low-intensity exercise was recommended to protect the arm from adverse events. However, supervision and compression garments were featured in the reviewed studies, and their impact and effectiveness need to be confirmed. In addition, no evidence was available to suggest that high-intensity weight training was harmful to the arm. Research efforts need to be made in this area.

• FINAL NUMBER STUDIES INCLUDED = 10
• TOTAL PATIENTS INCLUDED IN REVIEW = 192
• SAMPLE RANGE ACROSS STUDIES = 1–45 patients
• KEY SAMPLE CHARACTERISTICS: Adults with lung cancer

• PHASE OF CARE: All phases
• APPLICATIONS: Elder care, palliative care

Three of the 10 studies showed a significant reduction in fatigue with exercise, one using aerobic exercise, one using chest physiotherapy, and one using pulmonary rehab. The other studies showed improvement but did not reach statistical significance. All studies were level 4 or 5 evidence (low). Studies with significant results, however, were not similar in their exercise intervention. Exercise was safe and feasible for adults with lung cancer. All studies provided exercise under supervision, and most included aerobic and interval training

\"This current review shows that exercise is beneficial and safe in lung cancer-related fatigue; however, the studies are small and, without any control groups, are lacking clinically significant effects. Thus, exercises could be used in the management of cancer-related fatigue in lung cancer in view of the available evidence in other cancer cohorts with due caution. There is an urgent need of further research with adequate sample size, preferably randomized controlled trials, to evaluate the effect of exercise in this cancer cohort” (p. 10).

• Small number of studies
• Small sample sizes
• Most studies without randomization or control groups
• Studies retrieved and reviewed by one student and advisor

In light of studies on the effects of exercise in other diseases, exercise can be considered for the management of fatigue in patients with lung cancer with attention to performance status. Patients perhaps should undergo individual testing and exercise prescription. Additional research is needed.

Patients rinsed with 30 ml of calcium phosphate at least four times per day. Patients also received four topical treatments of 1% fluoride as neutral 2% sodium fluoride gel administered by tray at the screening visit and completed prior to hospitalization.

Patients in the control group received an aqueous 0.01% sodium fluoride rinse. Prior to transplantation, the control group received four topical treatments with a placebo gel administered with the same technique as the experimental group. During transplantation, patients used the sodium fluoride rinse at least four times daily, 30 ml each time.

Patients who developed severe mucositis were instructed to rinse up to 10 times per day with their solution.

All patients received acyclovir and antifungal prophylaxis per protocol.

• The study reported on 95 patients undergoing hematopoietic stem cell transplantation (HSCT).
• Patients receiving autologous HSCT had peripheral stem cells and granulocyte colony-stimulating factor (G-CSF).
• Patients receiving allogenic HSCT had bone marrow cells and methotrexate (MTX).
• The experimental group had 50 patients, and the control group had 47 patients.

This was a randomized, controlled trial.

The National Institute of Dental and Craniofacial Research scale was used.

The following were measured and recorded.

• Days to absolute neutorphile count (ANC) greater than 200 mm³
• Days to ANC greater than 500 mm³
• Days of mucositis
• Peak mucositis level
• Peak pain level
• Days of pain
• Milligrams of self-administered morphine
• Days of morphine
• Average length of stay (ALOS)

• Duration of mucositis was 7.2 days in the control group and 3.72 days in the caphosol group (p = 0.00096).
• The control group had a smaller percentage of patients experiencing no mucositis (19% versus 40%).
• Peak mucositis was significantly higher for the control group (p = 0.004).
• The experimental group experienced fewer days of pain, milligrams of morphine, and days of morphine.

• The study had an adequate sample size according to power analysis.
• Frequency, duration, and severity of oral inflammatory processes were significantly lower in the experimental group.

• Use of fluoride may have decreased infection.
• No comparison was provided between allogeneic and autologous transplantations and the presence of mucositis.

• Patients were instructed to swish around crushed ice cubes in their oral cavity from 5 minutes before until 30 minutes after IV administration of 5-fluorouracil (5-FU).
• Physician evaluators were blinded.
• Patients received five consecutive days of leucovorin (20 mg/m² per day) plus 5-FU (600 mg/m² per day) administered over a few minutes (Mayo regimen).
• Patients were evaluated for three consecutive cycles.

• The cryotherapy group consisted of 36 patients. Mean age was 62.6 years, with a range of 50–82 years. 
• The control group consisted of 40 patients. Mean age was 61 years, with a range of 42–78 years.
• Patients with head and neck cancer were excluded.
• Nine patients were unwilling to join the cryotherapy group because of tolerance to oral ice.

• Patients were instructed to complete a questionnaire one month after cryotherapy prior to the following course.
• Two blinded otorhinolaryngologists graded patients on a 0–4 scale.

• The percentage of patients free from oral toxicity was significantly higher in the cryotherapy arm (p < 0.01) based on physician evaluations.
• The percentage of patients not suffering from mucositis was significantly higher in the cryotherapy arm following the first and third cycles (p < 0.05) but also after the second chemotherapy cycle (p < 0.01).

• Researchers were unable to double blind cryotherapy.
• The sample size was small.
• Results depended on assessment at completion of cycles, so some changes may have been missed. This study would have benefited from having additional, earlier assessment times.

Assess efficacy of gabapentin in controlling hot flashes in women with breast cancer

Patients were randomized to placebo, gabapentin 300 mg/day, or gabapentin 300 mg three times a day for eight weeks.

• Women with breast cancer having an average of two or more hot flashes per day (N = 420).
• Evaluable data for 371 patients at four weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at eight weeks (113 placebo, 114 gabapentin 300 mg, 120 gabapentin 900 mg).
• Mean age: 55 years old
• Inclusion: Adult women with history of breast cancer and were having an average of two or more hot flashes per day; adjuvant tamoxifen use was permitted
• Exclusion: Currently receiving chemotherapy; use of venlafaxine, clonidine, or anticonvulsants not permitted; pregnancy, breastfeeding, use of steroidal contraception, coronary insufficiency, recent history of myocardial infarction, symptomatic cardiac disease, peripheral or cerebrovascular disease, stroke, syncope, or symptomatic hypotension; hepatic dysfunction (aspartate aminotransferase concentration above twice the upper limit of normal or bilirubin concentration above the upper limit of normal), renal dysfunction (serum creatinine concentration above 1–25 times the upper limit of normal); allergy to gabapentin

University community clinic oncology program

Randomized, double-blind, placebo-controlled multi-institutional trial.

• Hot flash diary one week prior to study and during weeks 4 and 8 of treatment
• Symptom inventory pretreatment, weeks 4 and 8 of treatment.

Decreases in hot flash severity scores between baseline and weeks 4 and 8, respectively were: 21% and 15% in the placebo group; 33% and 31% in the group assigned gabapentin 300 mg; and 49% and 46% in the group assigned gabapentin 900 mg. The differences between the groups were significant (p = 0.0001 at four weeks and p = 0.007 at eight weeks by analysis of covariance for overall treatment effect).

Gabapentin was effective in control of hot flashes at a dose of 900 mg/day but not at a dose of 300 mg/day.

• Long-term use of gabapentin not assessed 
• Withdrawal rate of 12% at four weeks and 17% at eight weeks

The study evaluated oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes.

Participants received oral clonidine hydrochloride 0.1 mg daily or placebo at bedtime for eight weeks.

The study enrolled 198 postmenopausal women (mean age 71 years) with breast cancer taking tamoxifen and stratified by time since menopause (less than three years, more than three years), duration of tamoxifen use (less than one year; longer than one year), and baseline frequency of hot flashes (less than 10 per day, more than 10 per/day). One hundred forty-nine (149) completed the study. Of the participants, 99 received clonidine and 99 received the placebo.

• Inclusion criteria:
  • Postmenopausal women who had been receiving adjuvant tamoxifen therapy for breast cancer for at least one month and reported at least one hot flash per day
  • Normal hepatic and renal function
• Exclusion criteria:
  • Premenopausal women 
  • Women receiving concurrent chemotherapy or endocrine therapy for breast cancer, hypertension therapy or concurrent treatment with monoamine oxidase inhibitors; L-dopa, piribedil, tricyclic antidepressants, or sedatives
  • Coronary insufficiency, recent history of myocardial infarction (within three months), symptomatic cardiac disease, peripheral or cerebrovascular disease, syncope, or symptomatic hypotension
  • Allergy or adverse reaction to clonidine

A community oncology clinic conducted the study.

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

Measures included:

• Daily hot flash diary for one week at baseline, during the weeks 4 and 8 during treatment, and four weeks after the end of treatment
• Symptom checklist

One hundred forty-nine (149) of 198 completed 12 weeks of follow-up (73 in clonidine group and 76 in placebo group.) Oral clonidine was shown to be effective. The mean decrease in hot flash frequency was greater in the clonidine group after week 4 (37% to 20%) and week 8 (38% to 24%). The clonidine group had more difficulty with sleep (41%–21%). A significant difference was seen in the mean change in QOL scale (p = 0.02) at 8 weeks.

Limitations included:

• Evaluation for eight weeks
• No evaluation of long-term effectiveness