To determine the effectiveness of early exercise intervention programs on the quality of life, physical function, and arm volume for breast cancer survivors immediately following breast cancer surgery

Participants were randomized into a control group and an intervention group. The control group received patient education only (tips about lymphedema awareness and prevention exercises from a general newsletter). The intervention group underwent a tailored comprehensive program (the RESTORE program), which consisted of a structured exercise regimen, a lymphedema prevention module, patient and diet education, and counseling sessions. The intervention occurred every 3 months, beginning from 4–12 weeks after breast cancer treatment. The final session occurred at 18 months.

• The sample (N = 82) was comprised of female patients.
• Mean age was 53.6 years with a range of 32–82 years.
• Patients were within 4–12 weeks of surgery and had stage I–III breast cancer.
• Of the sample, 46% had breast-conserving surgery, 79% had axillary node dissection, 59% received chemotherapy, 64% received radiation, and 71% had a mass body index of equal or greater than 25 kg/m².

The study took place across multiple in-patient and home settings in association with Wake Forest University Health Center.

Patients were undergoing transition from breast cancer treatment to active treatment for lymphedema.

The study used a single, blinded, randomized controlled design.

The effectiveness of the RESTORE program was measured using the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B), distance traveled during a six-minute walk (measured by a pedometer), and arm volumes measured at three-month intervals using the water displacement method. The FACT-B was a survey that assessed physical, social, and functional well-being of the participants.

Those in the exercise intervention had a significantly higher distances walked in the six-minute walk test than in the control group by the end of all the study (p = 0.00098). However, there was no statistical difference between the average FACT-B scores from the control and intervention groups. (p = 0.57). There also was no statistical significance between groups in terms of arm volume when compared with measurements at baseline and 18 months (p = 0.54).

There appears to be a positive correlation between the RESTORE program and physical function in individuals immediately after breast cancer treatment. Unexpectedly, this did not translate into a decrease in lymphedema-related symptoms (like edema) or social perceptions of the disease.

• The sample was small (N < 100).
• The intervention was expensive, impractical, or required extensive training for a long period of time.
• Subject withdrawals were greater than or equal to 10%.

Nurses should be aware of the symptoms that patients can present with after breast cancer remission. Nurses should encourage their patients to seek regular visits to their healthcare providers because this study showed that physical function can improve with more vigorous self-maintenance and early intervention. Further research should be conducted to determine the effectiveness of the RESTORE program as a standalone therapy.

To systematically review the literature on the prevention and palliation of multikinase inhibitor (MKI)-associated hand-foot syndrome (HFS) to identify areas for further clinical study and to provide a foundation for evidence-based guidelines for HFS management

DATABASES USED: PubMed, Cochrane Database of Systematic Reviews, BIOSIS, and CANCERLIT

KEYWORDS: Hand foot syndrome, hand foot skin reaction, acral erythema, palmar-plantar erythrodysesthesia, acral erythrodysesthesia, Burgdorf reaction, toxic erythema of the palms and soles. Medical subject headings (MeSH) included skin disease, hand injuries, chemically induced, antineoplastic agents, and protein kinase inhibitors. Names of specific agents also were entered into the MeSH search.

INCLUSION CRITERIA: English language clinical studies; meta-analysis, reviews, or practice guidelines; literature through August 31, 2008. Literature was categorized (C) according to the type of agent and cutaneous reaction.

• C1—Articles pertaining to MKI-associated HFS containing histology, pathogenesis, incidence, quality of life, impact, treatment, or prevention
• C2—Articles focused on MKI-associated skin reactions other than HFS
• C3—Articles focused on antineoplastic agents other than MKIs and HFS
• C4—Articles that did not focus on clinical details of pathophysiology or treatment of HFS (e.g., health policy, study design issues)

EXCLUSION CRITERIA: Conditions other than HFS, topics unrelated to antineoplastic therapy

TOTAL REFERENCES RETRIEVED = 2,069 abstracts 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: After screening for inclusion, 350 abstracts (17%) met criteria for inclusion in C1–C4 categories.

• FINAL NUMBER STUDIED INCLUDED = 56 articles categorized as C1 were reviewed and evaluated. Only those that fell into this category were discussed in this review. None of the citations on prevention or palliation approaches to HFS were randomized, controlled trials.

Prevention approaches for MKI-associated HFS included

• Screening for preexisting plantar hyperkeratosis (e.g., podiatry care)
• Prophylactic removal of hyperkeratotic areas (e.g., manicure or pedicure before and during treatment to remove hyperkeratosis)
• Use of prophylactic skin care (e.g., emollients, topical exfoliating products applied to calluses, pedicures, manicures)
• Protection of pressure-sensitive areas of the hands and feet (e.g., wearing well-fitting, soft shoes; cushioning of callused areas by soft or padded shoes)
• Use of prophylactic systemic treatments (e.g., administration of prophylactic pyridoxine [vitamin B₆], glucocorticoids, cyclooxygenase-2 inhibitors).

The following are recommendations on patient education prior to MKI therapy.

• Providers are encouraged to listen to patient concerns, offer options to enhance patient comfort, and identify treatment issues early.
• No studies were found that tested efficacy of patient education approaches for preventing hand-foot skin reactions (HFSRs) (e.g., written materials, videos).

Treatment and palliation for management of HFS symptoms:

• Grade 1 HFS
  • Dermatology referral and management, as appropriate
  • Use of keratolytics (e.g., 40% urea and/or salicylic acid) to aid in exfoliation of callused areas
  • Cushioning of affected regions with gel inserts in shoes or use of loose-fitting shoes or slippers
  • Frequent application of emollients and creams, especially to palms and soles, to maintain moisture and prevent breaks in skin integrity
  • Analgesics
  • Local/regional cooling (e.g., cool compresses)
  • Foot soaks in magnesium sulfate to soften calluses and reduce pain upon pressure
• Grade 2 HFS
  • All interventions as outlined for grade 1
  • Dosage or regimen adjustments of MKIs
  • Continue to control symptoms and relieve patient discomfort
• Grade 3 HFS
  • Topical therapy to reduce symptoms and prevent further progression (e.g., frequent use of creams and lotions, especially to palms and soles of feet; wet disinfectant to treat blisters and erosions; cortisone creams and topical antibiotics for severe forms of HFSRs)
  • Systemic strategies to reduce symptoms and prevent further progression (e.g., pyridoxine may be beneficial in doses of 50–150 mg/day)
  • Dosage or regimen adjustments of MKIs (e.g., interruption of MKI therapy for a minimum of seven days until toxicity is resolved to grade 0 or 1)

Authors stated that no evidenced-based treatment algorithms exist for cutaneous toxicities of the MKIs in the dermatologic or oncologic literature. It was noted that none of these recommendations were based upon strong evidence-based data and that none of the C1 articles were randomized, controlled trials designed to test HFS reactions management. It was revealed that clinical approaches to HFS are largely anecdotal, from case reports, based on practices during clinical trials of antineoplastic treatment, obtained from post-marketing practices, or extrapolated from approaches often used with chemotherapeutic treatments.

No actual convincing evidence was found in this review for any recommendation identified.

• Among all the C1 articles reviewed, none were randomized, controlled trials designed to test HFS management approaches.
• None of the ancillary, observational, or case control studies described in the literature reviewed were designed to test the effectiveness of HFS management interventions.
• Most information being used is anecdotal or based upon individual provider experience and preference.

This review points to the need for research to test and compare various recommendations for prevention and management of HFS on clinical and patient-centered outcomes.

Research is needed in the following.

• Appropriate and effective patient education for prevention
• How often the patient should be seen and assessed for HFS
• How to accurately diagnose mild HFS and recognize subsequent skin complications
• How to effectively treat without leading to increased HFS damage and symptoms
• Providing guidance on the best types of gel inserts, cushions, and soft footwear
• Identifying treatment strategies that are most effective at all grades of HFS
• Testing specific emollients or creams for preventive or reactive treatment of MKI-associated HFS

To determine if a mindfulness-based stress reduction (MBSR) intervention improves sleep quality in postoperative patients with breast cancer.

An MBSR intervention was implemented using a standardized MBSR manual and was led by trained instructors. The intervention included eight weekly MBSR group sessions lasting two hours each. Sessions included psychoeducation on stress response, gentle yoga, and mindfulness meditation. No additional content was added in regard to sleep problems. All participants were encouraged to practice MBSR at home for 45 minutes daily and were given CDs and meditation guides for home practice. All participated in a five-hour retreat after week 7. Assessments were performed postintervention and at 6 and 12 months.

• The study included 336 women in the intention-to-treat (ITT) analysis. The final sample was comprised of 264 women.
• Mean (standard deviation [SD]) age was 53.9 years (SD = 10.1 years) in the MBSR group and 54.4 years (SD = 10.5 years) in the control group.
• Participants had breast cancer and were 3 to 18 months postoperative.

• Multisite 
• Denmark

Participants were undergoing the transition phase of care after active treatment.

The study was a randomized, controlled trial with repeated measures.

• Medical Outcome Study (MOS) Sleep Scale (not validated in patients with breast cancer)
• Symptom Checklist-90-revised (SCL-90-R)
• Hot Flush Score (stated as validated, but no further information was provided on validity or reliability)

Sleep quality improved from baseline to postintervention for both groups, with statistically significant differences in mean scores for sleep quality for the MBSR group in two indices of the sleep problem index (p = 0.03). There were no significant differences between groups at the 6- and 12-month follow-ups. Change in overall sleep quality was also significantly better in the MBSR group from baseline to postintervention (p = 0.05) but with a small effect size (<0.3). Further quantile regression analysis revealed that those who participated in MBSR had a significantly smaller increase in sleep disturbances from baseline than the control group in the twenty-fifth percentile, although this effect was not significant across quartiles. The effects of MBSR on sleep quality were not modified by hot flushes or psychological distress.

MBSR has limited short-term but no long-term effects on sleep quality in postoperative patients with breast cancer. Effects on sleep quality are small and are not modified by hot flushes or psychological distress. Further study is needed to determine if MBSR is effective for patients with significant sleep problems immediately after surgery and if booster MBSR sessions have longer-term effects.

• The study had risks of bias due to no blinding and no appropriate attentional control condition.
• Measurement validity/reliability was questionable.
• Subject withdrawals were 10% or greater.
• Of the patients, 7% in the intervention group were either lost to follow-up or discontinued the intervention and about 15% in the control group were lost to follow-up. No analysis of differences was performed on those lost to follow-up and those who continued. Although not statistically significant, baseline sleep disturbance data showed lower results for disturbance in the intervention group, and ITT analysis was the last value carried forward. ITT analysis may have overstated the effects of MSRB in this case.

Further study is needed to determine if MBSR is effective for improving sleep quality in patients with breast cancer. Nurses should assess for sleep problems in patients with breast cancer across treatment and especially after treatment.

To evaluate whether a six-week supervised multimodal exercise intervention can reduce cancer-related fatigue levels.

The intervention involved having patients exercise for 2.25 hours for four days per week for a total of six weeks in a group session of dynamic exercises using heavy resistance, cardiovascular training, relaxation techniques, body awareness (i.e., stretching, breathing, yoga, and Pilates), and massage.  The study was wait-list controlled.

• The sample was comprised of 213 patients.
• Mean age was 47.5 years (range 20–65).
• In the control, 28% of patients were male and 72% were female. In the intervention, 20.8% of patients were male and 79.2% were female. 
• Mean days since diagnosis was 82/86.5, and 52% to 58% of patients had no evidence of disease at baseline.
• Of the patients, 103 had breast cancer and 29 had bowel cancer.
• Of the patients, 83.7% of the control and 82.7% of the intervention reported some kind of exercise at baseline.

• Single site 
• Outpatient 
• Copenhagen

Patients were undergoing the active antitumor treatment phase of care. 

This was a randomized, controlled trial.

Functional Assessment of Cancer Therapy-Anaemia Questionnaire (FACT-An) 

Improvement occurred in fatigue score in the intervention compared to the control (p = 0.002; effect size = 0.44).  FACT-An subscale score (13 items were related to fatigue, and seven were indirectly related) was also improved in the intervention compared to the control (p = 0.015). FACT-An improved (p = 0.009), and Anemia-ANS improved (p = 0.002). Well-being scores of Quality of Life (QOL) scores showed no difference.

Supervised exercise can have an effect on fatigue levels for patients during chemotherapy. Specific diagnoses and fatigue after treatment were not evaluated.

• There were risks of bias due to no blinding, lack of an appropriate attentional control condition, and sample characteristics [patients were self-referred to the program, suggesting a highly motivated group]).
• Participant withdrawals were 10% or greater.

 Patients experiencing fatigue during active treatment may benefit from supervised multimodal exercise.

To evaluate the effect of a multidimensional exercise program on managing symptoms in patients with cancer undergoing chemotherapy

Patients receiving chemotherapy participated in a structured, supervised exercise program, consisting of resistance-fitness training, massage, relaxation, and body-awareness training held in a workout room within the hospital, two to three times per week for a six-week period. Participants trained in mixed groups of seven to nine. Physiotherapists and a specially trained nurse, who participated in the physical training, supervised the program. Participants selected a total package of high or low intensity physical activity. They were not able select one activity over another.

• The study consisted of 54 patients with cancer.
• Participant ages ranged from 18-65 years.
• All patients had been diagnosed at least one month prior receiving chemotherapy for adjuvant or advanced disease and had World Health Organization (WHO) performance statuses of 0-1 (0-5 scale).
• Patients were excluded from the study if they had documented brain metastases, had received anticoagulation treatment or treatment for arrhythmia or myocardial infarction within the past three months, had dementia and psychotic conditions, or were unable to read and write in Danish.

The study was conducted at university outpatient and inpatient settings in Denmark.

This was a prospective, exploratory study.

Using semi-structured diaries, patients rated 12 symptoms, including lack of appetite, nausea and vomiting, diarrhea, paraesthesia, constipation, physical fatigue, treatment-related fatigue, muscle pain, arthralgia, and other pain, defined by Common Toxicity Criteria (CTC) daily using a 0-4 scale.

• During the intervention, patients reported decreases in 10 of 12 symptoms.
• Patients with evidence of disease scored symptoms higher than those without evidence of disease.
• Both groups responded positively to the intervention based on sum of symptom scores.

A six-week, multidimensional exercise intervention administered while patients were simultaneously receiving chemotherapy led to reductions in symptoms.

• The use of daily diaries is time consuming for patients.
• Some data was missing.
• Because this continued over time, participants may have recorded the previous score just to fill it in.
• An exercise program takes commitment. The length of time for classes varied between high- and low-intensity groups.
• Providing space for workout rooms accessible to inpatients and outpatients may be an issue for some centers.
• Each symptom was given equal weight whereas some symptoms may be perceived as more problematic for patients.
• This intervention requires a high level of knowledge and specific skills on the part of the individual who trains and supervises patients.

The guideline provides an algorithm for the screening and assessment of anxiety, a care map for anxiety in adults with cancer, an algorithm for the screening and assessment of depression, a care map for depression in adults with cancer, the Patient Health Questionnaire (PHQ 9) symptom depression scale and generalized anxiety disorder (GAD) items, and selected measures for depression and anxiety (modified).

• Before the implementation of guidelines, referral systems and resources should be identified and available in each institution.
• The guidelines are designed for healthcare providers, patients, family members, and caregivers to guide in the screening, assessment, and treatment approaches of adult patients with cancer who have anxiety and depression at any stage of the cancer continuum, regardless of cancer type, disease stage, or treatment modality. 
• All patients with cancer and cancer survivors should be evaluated for the symptoms of anxiety and depression with validated instruments at periodic times during the cancer care. Treatment recommendations are based on the levels of symptoms. Follow-up care and reassessment are important in this setting to monitor for follow-through, compliance with referrals, and pharmacologic management. If compliance is poor, develop a plan. After eight weeks of treatment, if symptoms are not improved or poor compliance is noted, alter the treatment course and add a psychological or pharmacologic intervention. The guidelines recommend that individual psychological interventions be delivered by a licensed mental health professional, which may include cognitive and behavioral strategies, education and relaxation strategies, group psychosocial interventions, and physician-prescribed antidepressants. 

• A guideline that has been adapted from another country often can't lend itself to different policies or cultural influences.
• Some of the recommendations were removed from the original guideline because of references to the Edmonton Symptom Assessment Scale screening measure, which is not widely used in the United States.

Nurses play a vital role in the early screening, assessment, and treatment of patients who may have significant symptoms of anxiety and depression. By screening and making appropriate referrals, we can impact the emotional, interpersonal, and financial costs for patients and reduce the economic impact for providers and the healthcare system.

To test the hypothesis that increased exposure to morning bright light would result in less fatigue during chemotherapy.

Women were randomly assigned to bright white light or dim red light groups. Light was administered via a light box. Sixty LED lights were used (red LEDs for the dim light groups and lights with a distribution of energy concentrated in the middle and long wavelengths for the bright light group). The light box was placed on a table or countertop at a distance of about 18 inches and was to be used for 30 minutes every morning on awakening. The boxes were modified to include an integrated meter that recorded the duration of light box use each day. Study measures were obtained at baseline, during cycle 1 treatments, the last week of cycle 1, a treatment week of cycle 4, and the last week of cycle 4.

• The study included 39 women, primarily Cacausian, with a mean age of  53.92 years (range 32–70).
• All patients were newly diagnosed with breast cancer who were set to receive four cycles of chemotherapy containing araC.

Patient homes in California

Patients were undergoing the active antitumor treatment phase of care.

The study was a repeated-measures, randomized, controlled trial.

• Wrist actigraphy
• Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF)

No significant changes were observed in fatigue scores for women in the bright light group. Those in the dim light group showed an average increase in fatigue of 11.7 points (p = 0.003) to the last week in cycle 1, and a 22.2-point increase (p < 0.001) by the last week of cycle 4. Scores on the emotional fatigue subscale showed improvement in the bright light group compared to baseline over all study time points, with significant differences shown at the end of cycle 1 (p = 0.006). All other subscales showed increased fatigue in both groups over time. No relationship existed between fatigue scores and actigraphy results. Patients adhered to light box use for an average of 48.7% of the days in the study, with no difference in compliance between groups.

Findings suggested that light therapy may be of some benefit to prevent worsening of fatigue during chemotherapy treatment.

• The study had a small sample size, with less than 100 patients.
• The study had a risk of bias due to no blinding.
• Unintended interventions or applicable interventions not described could influence the results.
• Patient withdrawals were 10% or greater.
• No other interventions that could have influenced fatigue were described or mentioned.

Light therapy may be helpful to patients in reducing fatigue during chemotherapy, particularly in the area of emotional fatigue. This is a low-risk intervention that might be useful. Patients could increase light exposure by spending more time outdoors or by using a light box.

The study analyzed the relative effectiveness and safety of azole antifungal prophylaxis with particular attention to the tri-azoles compared to fluconazole/itraconazole.

Patients at the Royal Melbourne Hospital with AML/MDS undergoing remission-induction chemotherapy from December 1998–January 2010 who received one day or more of azole prophylaxis were included.  Prophylaxis consisted of fluconazole 400 mg daily, itraconazole sodium 2.5 mg/kg twice daily, voriconazole 200 mg twice daily or posaconazole 200 mg three times daily with fatty food. These were started 1–2 days prior to chemotherapy and continued until neutrophil recovery (greater than 0.5 cells/L), occurrence of a confirmed or suspected invasive fungal infection, drug-related toxicity/intolerance, or the patient’s condition becoming palliative. Oral administration was preferred, fluconazole or voriconazole could be given via IV when a patient’s gastrointestinal absorption was considered inadequate.

216 patients were evaluated (57 in the fluconazole group, 59 in the itraconazole group, 82 in the voriconazole group, and 68 in the posaconazole group).

The median age per group was: fluconazole, 57 (range = 20–79); itraconazole, 55 (range = 20–79); voriconazole, 51 (range = 17–81); posaconazole, 51 (range = 19–78).

Regarding key disease characteristics, 197 patients had AML and 18 had transformed MDS. Median duration of neutropenia ranged from 13–16 days. 

Patient receiving TPN per group: fluconazole, 38%; itraconazole, 40%; voriconazole, 21%; posaconazole, 31%.

Fluconazole was used from December 1998 to September 2008, itraconazole was used from May 1999 to January 2003, voriconazole was used from November 2002 to August 2008, posaconazole was used from September 2006 to January 2010.
 

• Single site 
• Inpatient 
• Royal Melbourne Hospital

Active antitumor treatment

The study was a retrospective review.

• Receipt of total parenteral nutrition (TPN) was a marker of severe mucositis.
• Invasive fungal infection onset was defined as the first day of suspicious CT abnormality or positive microbiology or pathological test.  
• Breakthrough invasive fungal infections were defined as occurrence of invasive fungal infection in patients during \"-azole\" prophylaxis or within seven days of drug cessation.   
   

The majority of patients (213/216) underwent chemotherapy for remission-induction or re-induction or relapsed disease. The median duration of neutropenia for fluconazole/itraconazole was significantly longer than voriconazole/posaconazole (16 days versus 14 days, p = 0.003). TPN requirement was 39% versus 26% (p = 0.001), and median duration of prophylaxis was 18 days versus 22 days (p < 0.001).   
Breakthrough invasive fungal infection occurred in 27 patients comprising of probable/proven (11) and possible (16). The incidence of breakthrough invasive fungal infection was significantly lower in the voriconazole/posaconazole group (10 of 125; 8%) versus fluconazole/itraconazole (17 of 85; 20%) (p = 0.011). All probable/proven invasive fungal infections were molds, most commonly aspergillosis.  
Sub-therapeutic drug levels were common in itraconazole (42%), voriconazole (38%), and posaconazole (69%).  
 

In this institution, the use of voriconazole/posaconazole coincided with a significant decrease in the incidence of breakthrough invasive fungal infections.

Risk of bias:

• No control group
• No blinding
• No random assignment
• No appropriate attentional control conditions
• Sample characteristics*
• Findings not generalizable*

*Findings generalizable to only hematologic malignancies. The retrospective nature is not as strong in this study and, although some good information was shared, the results are not as useful to change practice.

This study compared different agents used for antifungal prophylaxis. There is always the need for education of patients and staff of the signs on infection while on prophylactic therapy and the education of taking the medication correctly and changing to an alternate therapy if the risk of impaired gastrointestinal function is greater for particular patients (i.e., severe mucositis).

To determine if electro-acupuncture (EA) is an effective adjunct treatment to manage postoperative pain, nausea, vomiting (PONV), and recovery in patients after a supratentorial tumor resection

In group A, acupuncture needles were inserted into the LI4, SJ5, BL63, LR3, ST36, and BG40 points, then EA stimulation was used with frequencies of 2 and 100 Hz alternating every three seconds at a level of maximum tolerance for each patient. The duration of the intervention was from the induction of anesthesia till the surgery ended. In group C, no needle was inserted.

• N = 88  
• AGE = Group A: 40.7 years (SD = 12.1 years), Group C: 39.1 years (SD = 10.9 years)
• MALES: 47%, FEMALES: 53%
• KEY DISEASE CHARACTERISTICS: Patients who received supratentorial tumor resections
• OTHER KEY SAMPLE CHARACTERISTICS: Patients received a needling test to exclude those who were resistant to acupuncture. Patients who developed a postoperative hematoma or infection were excluded. In addition, patients were excluded if they were obese, pregnant, taking any medications, or had cardiovascular or respiratory diseases.

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Operation room

• PHASE OF CARE: Multiple phases of care

• Double-blinded, randomized, controlled trial

• Postoperative pain on a 0–10 scale
• Incidence of PONV
• Dizziness and feelings of fullness in the head
• Appetite

After six hours of surgery, the Visual Analog Scale scores, the mean total bolus administration, and the effective number of PCIA bolus administrations in the EA group was statistically significantly lower than the control group. During the 6–48 hours, there were no differences in the mean total bolus administration, the effective number of bolus administrations, and the total fentanyl dose between the two groups. There were no differences in PONV between the two groups. Patients in the EA group experienced a lower incidence and degree of dizziness and feelings of fullness in the head compared to patients in the control group. Patients in the EA group could eat more on a liquid diet than patients in the control group 24 hours postoperatively.

EA can reduce postoperative pain, decrease the number of effective PCIA bolus administrations, improve appetite, and decrease dizziness and feelings of fullness in the head for patients who received supratentorial tumor resections.

• Small sample (< 100)
• Measurement/methods not well described
• Measurement validity/reliability questionable

These study findings show that EA may be used as an adjunct treatment to reduce postoperative pain, decrease the number of effective PCIA bolus administrations, improve appetite, and decrease dizziness and feelings of fullness in the head for patients receiving supratentorial tumor resections.

To investigate the analgesic efficacy of venlafaxine and gabapentin on acute and chronic pain after breast cancer surgery

Patients were randomized prior to surgery to one of three groups. The venlafaxine group received 37.5 mg of extended release venlafaxine once daily and a second placebo capsule at bedtime. The gabapentin group received 300 mg of gabapentin daily and another placebo capsule at bedtime, and the placebo group received placebo capsules daily and at bedtime. Medications were started the evening before surgery and continued for the first 10 postoperative days. Anesthesia was standardized. When patients complained of pain in recovery they were given a titrated dose of morphine until the VAS pain score was 30 or less. For the first 24 hours postoperatively, IV morphine at 20–50 mcg/kg was given to maintain Visual Analog Scale (VAS) at or below 30. For the remaining time to postoperative day 10, all patients were given acetaminophen and codeine every six hours and as necessary. Pain scores were recorded at rest and with movement at four, 12, and 24 hours on the first postoperative day, then daily for 10 days, then six months later.

• N = 150 
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had either radical or partial mastectomies with axillary dissections.

• SITE: Single site  
• SETTING TYPE: Multiple settings  
• LOCATION: Egypt

• PHASE OF CARE: Multiple phases of care

Double-blinded, randomized, placebo-controlled trial

• Visual Analog Scale (VAS) for pain
• Morphine consumption

Compared to the control group, VAS scores from the second to the tenth day postoperatively were significantly lower in the gabapentin group (p < 0.0003). Compared to controls, VAS scores for pain with movement were significantly reduced for those receiving venlafaxine during days 8–10 (p < 0.0002). Total morphine consumption in the first 24 hours was lower in the gabapentin group compared to both other groups (p < 0.0001). Significantly more patients in the control and gabapentin groups were using opioids for pain at six months (p < 0.05). There were differences among groups in the type of pain reported at six months, but there were no consistent or significant differences in overall pain results. Patients who received venlafaxine had lower prevalence of burning and stabbing or pricking pain. There were no differences between groups in terms of side effects.

The perioperative administration of gabapentin was associated with decreased pain during the acute phase after breast cancer surgery, but it did not appear to have an effect on the incidence of chronic pain after six months postoperatively. The administration of perioperative venlafaxine may have had a beneficial effect on chronic postmastectomy pain syndrome.

• Other limitations/explanation: There was no description or analysis of differences by type of surgery, and it could be expected that individuals who had more extensive procedures could have had more acute and chronic pain.

The findings of this study showed that perioperative gabapentin was associated with reduced pain in the acute postoperative period among women with breast cancer. The use of venlafaxine may have some benefit for long-term neuropathic pain postmastectomy, but these findings were not definitive. This adds to a growing body of evidence regarding the efficacy of gabapentin in reducing acute surgical pain and points to the need for additional research regarding interventions and the potential role of venlafaxine for postmastectomy pain syndrome.