To assess the usefulness of gabapentin in the treatment of cancer-related neuropathic pain

Patients who met the eligibility criteria of a score of 5 or greater on a numeric pain rating scale were entered. Gabapentin was begun at baseline at 200 mg and titrated to a maximum dose of 2,400 mg per day. Patients were asked to keep a pain diary and were assessed by a clinician throughout the 15-day study period.

• Twenty participants (10 men, 10 women) with a median age of 62 years (range of 31–74 years) were included in this study.
• Participants had a variety of tumor types, with the most common being colon and lung cancers.
• Of the total sample, 83% were inpatients, all were on opioids, 46% also were receiving nonsteroidal anti-inflammatory drugs, 79% were taking anticonvulsants, and 67% were on antidepressants.
• The range of the opioid dose was 6–600 mg.
• Fifty-four percent had pain from the tumor rather than from the treatment, and only 29% had actual peripheral neuropathy.

The study was conducted in a single-site inpatient setting in Japan.

This was an open-label, prospective study.

Measurements included a numeric pain rating scale using the Brief Pain Inventory, the McGill Pain Questionnaire, a numeric pain relief scale, and the Patient Global Impression of Change scale.

A significant reduction was noted at various time points for worst, least, and average pain on the numeric scale (p < 0.004). Mean change in scores from baseline ranged from 0.6 to 1.3. No differences were found in any other outcome measure.

A statistical reduction in pain occurred as measured on the five-point numeric rating scale; however, the change was relatively small.

• The study had a small sample size, with less than 30 participants.
• Neuropathic symptoms were found to be related to treatment in only 46% of patients in the study.
• Pain was measured by various means, but no direct measures were specific to neuropathy.
• No discussion took place as to whether there were any changes in analgesic regimens provided during the study.
• No appropriate control or comparison groups were used.

The study findings do not provide strong support for the effectiveness of gabapentin for the management of cancer-related neuropathic pain or other symptoms.

To evaluate the efficacy and safety of aprepitant plus standard therapy (granisetron and dexamethasone) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in Japanese patients with cancer undergoing treatment with chemotherapy including a highly emetogenic cisplatin-based regimen (≥ 70 mg/m²)

Patients were allocated to three groups.

• The aprepitant 125/80 mg group received 125 mg on day 1 and a dose of 80 mg on days 2–5.
• The aprepitant 40/25 mg group received of 40 mg on day 1 and a dose of 25 mg on days 2–5.
• The standard therapy group received an oral administration of placebo on days 1–5.

All patients received standard therapy consisting of 40 µg/kg IV granisetron on day 1 and dexamethasone. Concomitant use of other antiemetics was prohibited from 48 hours before day 1 to the morning of day 6, except for rescue therapy for CINV.

• The study looked at 439 participants.
• Mean age for the 125/80 group was 60.5 years (SD = 9.7 years); for the 40/25 group, 63.3 years (SD = 9.4); and for the standard group, 62.2 years (SD = 9.8).
• Gender of patients was 24% female and 76% male.
• Patient diagnoses were
  • 72% respiratory
  • 15% urogenital
  • 5% digestive
  • 5% eyes/ears/nose/throat
  • 3% other
• Mean cisplatin dose (mg/m²) for the 125/80 group was 76.9; for the 40/25 group, 76.9; and for the standard group, 76.2.
• Percentage of patients with a history of morning sickness was 42%; 8% of patients had a history of motion sickness.
• Patients receiving cisplatin chemotherapy was 17%; chemotherapy except cisplatin, 21%, and CINV except cisplatin chemotherapy, 40%.

The study was conducted at multiple sites in Japan.

Study participants were in active treatment.

This was a phase II, placebo-controlled, double-blind, randomized parallel comparative study.

• Patients recorded in a symptom diary the onset of vomiting and nausea intensity on a 4-point scale, and the name and dose of any rescue therapy used along with the date and time from day 1 to the morning of day 6.
• Safety was evaluated based on physical examination findings (vital signs, weight, general lab tests, lab values).
• Toxicity was evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTAE).

In the three study groups, the percentage of patients with complete response (no emesis and no rescue therapy) was 50.3% (standard therapy), 66.4% (aprepitant 40/25 mg), and 70.5% (aprepitant 125/80 mg). Efficacy was significantly higher in the aprepitant 40⁄25 mg and 125/80 mg groups than in the standard therapy group (p = 0.0053 and p = 0.0004, respectively), and efficacy was the highest is the aprepitant 125/80 mg group. The delayed phase efficacy was similar to the overall phase efficacy, indicating that aprepitant is effective in the delayed phase when standard therapy is not very effective. Aprepitant was generally well tolerated.

Aprepitant was shown to be more effective in the overall phase, including both acute and delayed, when compared to the standard group, irrespective of sex, age, or previous treatment with cisplatin.

• Limited information was provided regarding measurement tools.
• The potential for anticipatory nausea was not addressed, especially in patients who had received previous emetogenic therapies.

Aprepitant used in combination with 5-HT₃ receptor antagonists and a corticosteroid is effective in preventing CINV associated with highly emetogenic agents.

To compare the effectiveness of oral versus IV 5-HT₃s for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving R-CHOP or CHOP chemotherapy

Data were obtained from medical records of patients who received CHOP or R-CHOP as initial chemotherapy from 2006–2012. Symptoms for five days from the start of treatment were investigated. Risk factors influencing CINV were also investigated. CINV prophylaxis was an 5-HT₃ alone.

• N = 72   
• MEAN AGE = 68 years (SD = 12.1)
• MALES: 45.33%, FEMALES: 44.66%
• KEY DISEASE CHARACTERISTICS: Non-Hodgkin lymphoma

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Japan

PHASE OF CARE: Active antitumor treatment

Retrospective cohort comparison

Complete response (CR) defined as no vomiting and no use of rescue medication.

CR was observed in 80.6% of patients. No significant differences were observed in the CR rate between those who were given oral or IV antiemetics. Female gender and an age younger than 70 years were independent predictors of CINV.

IV and oral 5-HT₃ had similar efficacy for CINV prevention; however, 5-HT₃ alone may not be sufficient for prophylaxis for individuals with greater risk.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Oral and IV 5-HT₃ achieved similar results for CINV prophylaxis. Female gender and younger age were independent risk factors for CINV.

To evaluate the effects of alvimopan on postoperative gastrointestinal (GI) function and length of hospitalization.

Alvimopan is an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier and, therefore, acts on the peripheral opioid receptors in the GI tract without affecting analgesia in patients taking opioids. Doses used in the study were 1 mg and 6 mg by mouth. On the day of surgery, patients were randomly assigned in equal proportions to one of three arms using computer-generated randomization stratified according to type of surgery. The three arms were 1 mg of alvimopan, 6 mg of alvimopan, or an identical appearing placebo. Patients took the drug or placebo two hours before surgery and then twice daily postoperatively until the first bowel movement, until discharge from the hospital, or for a maximum of seven days. Patients were seen twice daily by the research team, from 6 am to 8 am and then from 4 pm to 6 pm.  At each visit, patients were asked about time of first passage of flatus and first bowel movement. Oral intake was measured until patients could tolerate regular meals. Subjects were considered ready for discharge if they had adequate oral intake to discontinue IV fluids, GI function had returned (defined as passage of flatus), they were afebrile, and they were free of major complications.

• The study reported on a sample of 78 patients who were generally healthy or had well-controlled systemic disease.
• Patient age ranged from 18 to 78 years.
• Patients were undergoing abdominal surgery (partial colectomy: n = 15; total abdominal hysterectomy: n = 63) with general anesthesia.
• Patients were included in the study if they were receiving opioids postoperatively for pain.
• Patients were excluded if they had received epidural administration of analgesia, had used corticosteroids or immunosuppressive drugs concomitantly within two weeks or opioid analgesics within four weeks before surgery, were likely to receive nonsteroidal anti-inflammatory drugs (NSAIDs) after surgery, had Crohn disease, or had a history of abdominal radiation therapy or treatment with vinca alkaloids. 

• Washington University in St. Louis, MO
• January 4 to July 22, 2000

This was a randomized, placebo-controlled study.

• Enrollment of 26 patients per group provided 95% power to identify a significant difference of one day in time to fitness for discharge between the 6-mg dose group and the placebo group at an alpha level of 0.05 with a two-tailed logrank test.
• Time to events (time in hours since end of surgery) was compared among groups using the logrank test. Other statistical analyses were described in detail.
• For patients who withdrew, administration of the drug or placebo was stopped; however, evaluation of the patients continued and all available data were entered into the analysis.
• Demographic data and type and duration of surgery were recorded.
• Primary efficacy outcomes were time to first passage of flatus, time to first bowel movement, and time until patient was ready for discharge.
• Secondary outcomes were time to first ingestion of solids, time until actual discharge, and visual analog scores (VAS) for nausea, abdominal cramping, itching, and pain.
• Severity of nausea, abdominal cramping, pain, and itching were also recorded using 100 mm VAS.
• Total daily use of opioids was also recorded.

• Twelve patients withdrew from the study (four in the placebo group and eight in the 1-mg dose group); however, none were from the 6-mg arm of the study.
• Time to recovery of GI function was significantly shorter in the 6-mg dose group than the placebo group.
• Median time to first passage of flatus decreased from 70 to 49 hours (p = 0.03), time to first bowel movement decreased from 111 to 70 hours (p = 0.01), and the time until patients were ready for discharge decreased from 91 to 68 hours (p = 0.03).
• Oral consumption and actual discharge occurred significantly earlier for the 6-mg dose group.
• VAS scores for pain, itching, and abdominal cramping were similar in the three groups. In contrast, nausea scores were significantly reduced in the 6-mg dose group compared with the 1-mg dose and placebo groups (p = 0.003).
• No vomiting occurred in the 6-mg dose group compared with 23% and 26% in the placebo and 1-mg dose groups, respectively (p = 0.03).

The 6-mg dose of alvimopan improved all major outcomes, with or without correction for the type of surgery. Analgesic efficacy of opioids was not affected by the study drug, and no adverse events occurred.

• The study was funded by the pharmaceutical company Adolor Corporation, a grant from the National Institutes of Health (NIH), and two other local funds.
• Two authors were employees of Adolor Corporation and contributed to the study design and statistical analysis.

To explore the effectiveness of colchicine in patients with slow-transit constipation not relieved with previous treatment.

Patients with refractory constipation were referred from gastroenterology clinics affiliated with Shiraz University of Medical Sciences in Iran. Patients initially were screened to rule out structural constipation, and transit time was measured. Patients were randomly assigned to colchicines 1 mg daily for two months (group A) or placebo starch capsule daily for two months (group B). Study assessments were done every two weeks for eight weeks.

• The study reported on a sample of 60 patients.
• Mean patient age was 38.94 years in group A and 35.47 years in group B.
• The study comprised 26 women and 4 men in group A, and 21 women and 9 men in group B.
• Patients had a diagnosis of constipation and slow-transit time; history of unsuccessful treatment with bulking agents, stimulant laxatives, and osmotic agents; and Rome II criteria validation of constipation diagnoses.

• Single site
• Outpatient
• Shiraz University of Medical Sciences in Iran

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

Knowles Eccersley Scott Symptom (KESS) scoring system

• A significant difference (p = 0.0001) existed in two-month mean KESS scores for the colchicine group (11.67, SD = 3.91; baseline: 18.13, SD = 5.43) compared to the placebo group (18.66, SD = 3.72; baseline: 20.13, SD = 3.86).
• No significant side effects were reported in the treatment or placebo groups. 
• Open-label follow-up for one month with the placebo group showed a 90.48% significant symptom improvement (p = 0.0001) compared to original response rates.
• No relapse in symptoms were reported from the original colchicine group.

Colchicine administration showed effectiveness in select populations.

• The sample size was small (fewer than 100 patients).
• The study took place at a single site, used a selective referral source, and did not assess efficacy of colchicine in conjunction with chronic pain or chronic opioid use.

Colchicine may be effective for short-term use in the treatment of slow-transit constipation, but further studies are needed to assess its effectiveness in an oncology population with chronic opioid use.

STUDY PURPOSE: To summarize systematic reviews that compared the efficacy, tolerability, and safety of cannabinoids with placebo or other antiemetics among patients of any age with any type of cancer

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 6 systematic reviews
• TOTAL PATIENTS INCLUDED IN REVIEW = Not reported
• SAMPLE RANGE ACROSS STUDIES: Not reported
• KEY SAMPLE CHARACTERISTICS: All age groups were included (ages 3.5–82 years) with all types of cancers; cannabinoids included dronabinol (7.5–30 mg), levonantradol (1.5–3 mg), nabilone (1–7 mg), or whole plant extracts.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Pediatrics, elder care, palliative care

Moderate quality evidence exists that pharmaceutical cannabinoids are less tolerated and less safe than placebo or conventional antiemetics. Insufficient evidence exists to determine if cannabinoids are more efficient than newer antiemetics. The number needed to treat with cannabinoid compared to placebo or conventional antiemetics to achieve complete control of CINV is four patients. The number needed to harm with cannabinoid compared to placebo or conventional antiemetics is six patients.

A narrow range of patients achieve complete control of CINV with cannabinoid versus patients who experience harm with cannabinoids. Insufficient evidence exists regarding the efficiency of cannabinoids versus newer antiemetics.

• Mostly low quality/high risk of bias studies

Cannabinoids should be considered for the treatment of uncontrolled or breakthough CINV but not as a first-line antiemetic for CINV.

PHASE OF CARE: Multiple phases of care

This update includes information from 14 clinical trials (eight randomized) involving 2,899 patients published since 2009. The quality of evidence and the strength of recommendations were guided by criteria from the Infectious Diseases Society of America and the United States Public Health Service grading systems and are presented in table format.

Only eight of the 14 studies considered were randomized, controlled trials.

Unlike previous versions, the newest guidelines provide separate recommendations for allogeneic HSCT in the pre- and postengraftment phases and in the presence or absence of GVHD. If GVHD is present, posaconazole is considered the drug of choice while fluconazole use is discouraged. Because the labeling of antifungal compounds can vary by country, the guidelines may not necessarily follow approved indications. They do, however, reflect published evidence.

To determine the overall symptom benefit of various physical therapy (PT) modalities applied on patients with head and neck cancer and lymphedema

This was a retrospective chart review of 32 patients with head and neck cancer who participated in physical therapy from August 2008 to July 2010. Patients were excluded if three or more variables were missing from the chart.

• N = 20  
• AVERAGE AGE = 54 years (SD = 12 years)
• MALES: 80%, FEMALES: 20%
• KEY DISEASE CHARACTERISTICS: All patients received surgical treatment with radiation and/or chemotherapy. Patients had head and neck cancer-related lymphedema. 
• OTHER KEY SAMPLE CHARACTERISTICS: Information gathered included body mass index, alcohol use, tobacco use, chief complaints, physical examinations of lymphedema, measurements of head and neck pre- and post-PT, presence or absence and intensity of pain, PT modalities, and number of sessions. The average time span from diagnosis to the start of physical therapy was 65.4 months (SD = 26 months).  

• SITE: Brazilian Institute of Cancer Central
• SETTING TYPE: Outpatient physical therapy
• LOCATION: Brazil

• PHASE OF CARE: After physical therapy

This was a retrospective study. The authors conducted a chart review of 20 patients who participated in physical therapy for complaints of swelling and pain related to head and neck surgery.

• Physical examination for assessment of lymphedema with a tape measure
• Occurrence and intensity of pain (Visual Analog Scale [VAS] from 0–10)
• Physical therapy modalities
• Number of physiotherapy sessions

• 100% of patients received program education.    
• 85% of patients experienced pain. This measure reduced to 70% by the end of the study.  
• Pain intensity reduced from 7.8 (SD = 2.2) to 3.6 (SD = 1.6) on the VAS (p < 0.001).
• Lymphedema volume reduction was successful (p < 0.05).  
• Modalities varied and included strategic manual lymphatic drainage versus physiologic manual lymphatic drainage (85%).
• Facial exercises were done by 75% of patients.
• Shoulder and neck exercises included stretching (80%), strengthening (55%), and range of motion (45%). 
• The average number of sessions was 23.9 (SD = 14.8) twice per week.  
• Compression therapy recommendations were documented for 70% of patients.

This study examined variables retrospectively to assess which practices might prove meaningful in a prospective study of patients with head and neck cancer. Pain would be an important symptom to study because of the interval between diagnosis and referral to physical therapy. Multiple physical therapy modalities were used, and a study supporting this would be useful. The findings from this study provided valuable information regarding designing future prospective studies.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 

The duration between diagnosis of disease and referral to physical therapy was greater than two years in most cases. Excellent pain assessment skills are needed for this patient population because stiffness and tightness are usually caused by fibrosis. Fibrosis is progressive and needs to be addressed early. Physical therapy might be beneficial in the management of lymphedema.

To assess the efficacy of Biafine cream in preventing grade 2 acute radiodermatitis.

• Biafine cream was applied twice daily to the skin within the treatment field, starting on first day of radiation therapy (RT) treatment and ending two weeks after RT.
• No application of ointment within four hours prior to RT was allowed.
• No other prophylactic agents were to be applied to the RT field during the course of RT.
• Application of ointment was permitted within four hours before RT.
• Patients were given general skin care recommendations at the start of RT.
• Patients who developed grade 2 radiodermatitis had the option to withdraw from study and be treated with other topical agents or to continue with Biafine cream.

• The sample was comprised of 60 women.
• Median age was 49 years (range 25–77).
• Patients had breast cancer and were treated with lumpectomy.
• Treatment lasted for five weeks, with a total dose of 5,000 cGy in 200 cGy fractions and no boost.
• Patients were treated on a 6-mv photon accelerator.
• All patients wer treated with concomitant adjuvant chemotherapy.

Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada

Skin within the RT field was examined before the initiation of RT, at weekly intervals, and at two and four weeks after treatment by a radiation oncologist or a dedicated radiation technologist.

The Skin Assessment Questionnaire was scored according to the National Cancer Institute of Canada skin radiation toxicity criteria.

The self-administered questionnaire incorporated items from the instrument developed for the Ontario Clinical Oncology Group trial of hypofractionated RT after lumpectomy in women with node-negative breast cancer.

The study was an exploratory, phase II, intervention trial.

• Maximum skin toxicity observed during the five-week course of treatment was:
  • Less than grade 2 toxicity (15%; n = 9)
  • Grade 2 (83%; n = 50)
  • Grade 3 (2%; n = 1)
  • Grade 4 (0%; n = 0).
• The majority of dermatitis was observed after three weeks of RT.
• Eight patients started Flamazine™ (Smith & Nephew, Inc.) cream with grade 2 desquamation.
• Most patients subjectively felt that Biafine cream was soothing.
• No treatment delays or interruptions were observed due to skin toxicity.

The majority of patients who underwent concomitant chemotherapy and RT for breast cancer developed grade 2 radiodermatitis with the use of Biafine cream.

• There was a wide range of RT start times from the start of chemotherapy.
• It was not possible to compare to a control group to determine comparative effects.

To provide a prospective evaluation of pneumatic compression therapy in patients with breast cancer-related lymphedema

During phase I, adjunctive intermittent pneumatic compression (IPC) was assessed for its role as a component of the initial decongestive therapy with previously untreated lymphedema. Phase II was a prospective study to evaluate adjunctive benefit to IPC for maintenance. All patients received standard decongestive lymphatic therapy, which included MLD, compressive wrapping, and decongestive exercises. Each patient received 10 days of daily decongestive lymphatic therapy. The study group had IPC applied to the affected arm daily for 30 minutes, in addition to the treatment as noted previously.

• Patients were included in the study if they presented with lymphedema related to breast cancer, defined as greater than 20% in volume compared to the other arm.
• There was a 12-week interval between cancer treatment and enrollment to study.
• Patients were excluded from the study if there was evidence of bilateral disease, breast cancer recurrence, active clinical infection, or clinically evident venous occlusion.

The study took place at Stanford University in California.

The study used a randomized prospective design.

• Assessments of limb volume, tissue elasticity, and joint mobility were performed at enrollment and on days 10 and 40 of the study.
• Water displacement volumetry was used.
• Skin tonometry was used to determine tissue elasticity.
• Goniometry was used to assess shoulder, elbow, and wrist joints range of motion.
• Data analysis was done using both paired and unpaired t-tests and analysis of variance.

In phase I, 23 women were recruited; 12 patients were randomized to group receiving DLT and IPC, while 11 were randomized to the group receiving DLT alone. After two weeks of treatment, reduction in volume of edematous arm was 45.3% for group 1 and 26% for group 2 (p < 0.05). Both groups showed no sign of improvement in skin elasticity study pre- or post-treatment. Also, 48% of patients had objective evidence of impaired range of motion at baseline. After initial therapy, joint mobility improved uniformly (p < 0.011) between both groups. In phase II, 27 patients were recruited. During a month of self-administered treatment, there was a mean increase in volume of the treated limb in group 1 with DLT alone. During the month of therapy, which included self-administered DLT and IPC, there was a mean volume reduction (p < 0.05). Skin elasticity showed no difference between the groups. Data collected poststudy showed that 20 of the 25 patients elected to continue using the IPC. Measurements showed additional reduction of limb volume.

IPC, when used as an adjunct to the other established elements of DLT, provides an enhancement of the therapeutic response.

Initial cost of pneumatic pumps might limit applicability, but researchers noted that documented improvement of lymphedema may offset the cost of care.