To demonstrate that one single fixed dose of pegfilgrastim (PEG) was not inferior compared to daily doses of filgrastim after high-dose chemotherapy (HDC) and autologous peripheral stem cell transplant.

Comparisons between two different granulocyte colony-stimulating factors (G-CSFs) (i.e., PEG and filgrastim) were highlighted in this article. The researcher wanted to reveal that PEG is the same high quality as filgrastim after receiving HDC and peripheral blood stem cells starting from day 1. A single fixed dose of PEG was given 24 hours after stem cell infusion.  In the control arm, 5 mcg/kg/day of filgrastim was given from day 1 until absolute neutrophil count (ANC) recovered to greater than .5x 10⁹/l.  Each setting followed its own supportive care and prophylaxis guidelines; however, all patients received quinolone prophylaxis.

• Seventy-seven of 80 patients were enrolled (three were excluded).
• Patients included were older than 18 years.     
• Fifty-six percent of patients were male and 44% were female. 
• Key disease characteristics were multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, acute leukemia, and solid tumors.
• Other key sample characteristics were duration of severe neutropenia, ANC recovery days, febrile days, requirement of antibiotics, disease status, and conditioning regimen.

• Multi-site (three)  
• Inpatient and outpatient 
• The locations were not specified.

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

This was an open-label, randomized study with a noninferiority design.

• Duration of severe neutropenia (ANC <.5x10⁹/l)
• Number of days to achieve ANC greater tha 1.0x10⁹/l
• Number of days with fever greater than 38°C
• Duration of antibiotic and antimycotic therapy
• Number of documented infections
   

This study illustrated that the use of a single fixed dose of PEG was not inferior to the use of daily filgrastim. There were no significant differences in measured outcomes between the two groups and no differences in treatment side effects.

PEG can be use alternately to filgrastim as it is only given as one single fixed dose of 6 mg as compared to daily doses of filgrastim.  Infection-related outcomes studied were not different between these two treatment approaches.

• Small sample (<100)
• No blinding, with risk of bias. 
• Other prophylactic treatments varied at different study settings, so care to prevent infections was not consistent for all patients in the study.

Use of a single dose of PEG rather than daily injections of filgrastim may be a useful alternative for these types of patients in order to avoid multiple injections.  Findings of this study were limited by sample size, study design issues, and the fact that other prophylactic treatment was not consistent throughout the sample.  Further research in this area will be helpful to confirm differences in the relative equivalency of these two approaches.

To compare placebo to sucralfate for prevention of mucositis in high-dose chemotherapy and bone marrow transplant (BMT)

Treatment was started one day before the regimen. Patients received one 2 g dose pack every three hours during the day and once during the night if awakened for a maximum of 7 per 24 hours until bone marrow (BM) recovery or end of mucositis.

The study reported on 102 patients hospitalized for allogeneic or autologous BMT.

The study was conducted between April 1991 and November 1993.

This was a prospective, randomized, double-blind study.

Patients were examined twice weekly by two physicians only, recorded prospectively, according to adapted Oral and Maxillofacial Surgeon (OMS) criteria for grafted patients.

• Slightly less patients in the sucralfate group (84%) experienced any grade mucositis compared to placebo (88%).
• Incidence of grade 3-4 mucositis was lower in the sucralfate group (29%) versus placebo (47%) (p = 0.07).
• The rate of severe mucositis was decreased possibly because of mechanical mouth rinses.
• When adjusted for total body irradiation (TBI), the p value for frequency of grade 3–4 mucositis in patients who received sucralfate versus placebo was 0.06.

• Long-term administration of sucralfate was not possible in this patient population because of nausea and vomiting.
• This study was conducted more than 20 years ago.
• The summary claims effectiveness for oral and intestinal mucositis; however, data does not support this claim.

To evaluate the safety and potential efficacy of acupuncture in the treatment of arm lymphedema in women with breast cancer-related lymphedema

Each patient was given acupuncture treatment twice weekly for four weeks. Treatments lasted 30 minutes, as 14 needles were inserted at apecific points determined on the basis of history and consensus of experienced acupuncturists.  Arm circumference was measured before and after each treatment.

• The study consisted of 33 patients with a mean age of 55 years.
• All of the participants were female and had breast cancer-related arm lymphedema.
• Time from surgery was a median of 3.9 years. 
• Most patients were reported to be on standard lymphedema therapy prior to enrollment.

This was a single-site, outpatient study conducted at Memorial Sloan-Kettering Cancer Center in New York.

This study has clinical applicability for late effects and survivorship.

This was a prospective trial.

• Arm circumference was measured.
• The percent change in lymphedema was calucated by taking the largest pretreatment difference between arms minus the same site posttreatment difference and dividing that number by the largest pretreatment difference.

• Just more than three-fourths of the patients (76%) received all intervention sessions. Of these, 33% showed reduction of 30% or more in lymphedema and 55% showed reduction of 20% or more. Mean reduction in the extent of lymphedema was 0.90 cm (95% confidence interval [CI], 0.72–1.07, p < 0.0005). 
• A segment of patients (12%) reported sustained improvement for four months during follow up; however, the method of obtaining this information was not clearly described. 
• Additionally, 36.4% of patients reported mild bruising or minor pain or tingling in the arm or shoulder at least once. One patient experienced a transient increase in lymphedema.

Findings suggest that acupuncture can be safely provided to patients with arm lymphedema. However, the benefit is unclear because of study design limitations and the fact that the mean change in lymphedema was very small.

• The sample size was small with fewer than 100 patients.
• A risk of bias exists because no control group, blinding, or random assignment was used.
• Unintended interventions or applicable interventions that were not described could have influenced results.
• The measurement methods were not well described.
• The measurement validity and reliability was questionable.
• The method of lymphedema measurement was not as rigorous as possible. The actual “standard” treatments used are not described, and it is not known if any changes occurred in the standard approaches during the study period, such as activity changes. 
• The report of duration of effect on follow-up was not clearly described.

This study provides insufficient evidence to support efficacy of acupuncture for lymphedema management.

To evaluate the safety and effectiveness of acupuncture in women diagnosed with chronic lymphedema

Women with chronic lymphedema after breast cancer surgery received acupuncture twice a week for four weeks using Acupoint prescription, chosen by consensus from members of the Memorial Sloan Kettering Cancer Center Integrative Medicine Service certified acupuncturists.

• The study sample (N = 9) was comprised of female patients aged 18 years or older.
• Median age of patients was 54 years.
• All patients had lymphedema (arm circumference greater than 2 cm in comparison to unaffected arm) for at least six months and no more than five years as a result of surgery or radiation therapy for breast cancer.
• Patients were excluded from the study if they had previous acupuncture treatment for lymphedema or current use of diuretics.

The study took place at the Integrative Medicine Service and Department of Epidemiology and Biostatistics at the Memorial Sloan-Kettering Cancer Center in New York.

The study has clinical applicability for late effects and survivorship.

The study used a prospective pilot design.

• Upper extremity volume was measured at two places on both the affected and unaffected extremities. The site with the greater difference between the affected and unaffected arms was used to determine the baseline measurement and assess outcome by comparing changes in the baseline measures.
• Positive response was considered to be 30% reduction in the difference in size between affected and unaffected upper extremities after four weeks of treatment.

After nine subjects were treated, four women demonstrated a 30% reduction in limb volume after four weeks of treatment, with no significant adverse events occurring. Some patients did experience minor toxicities, such as slight bruising or minor pain at acupuncture site shortly after treatment.

The pilot study suggests that acupuncture for women with arm lymphedema may be practical and was not associated with significant adverse effects. Further research in this area to establish safety and begin to evaluate effectiveness is planned.

• The sample size was small with less than 30 patients.
• Sample characteristics present a risk of bias.
• Measurements and methods were not well described.

Additional robust randomized controlled trials are needed to evaluate the use of acupuncture for the treatment of lymphedema.

• Massage therapy (i.e., Swedish, light touch, foot); manipulation of soft tissue
• Average time: 20 minutes for inpatients and 60 minutes for outpatients
• Tactile stimulation is essential to development and survival.

• N = 1,290 patients
• No demographics were provided.
• KEY SAMPLE CHARACTERISTICS: Fatigue was a presenting symptom in 312 patients.

• SETTING TYPE: Inpatient and outpatient settings
• LOCATION: A large, specialized cancer center

• PHASE OF CARE: Active treatment, long-term follow-up

• Retrospective review of clinical data from first massage episode

• Numeric rating scale (0–10) of extent to which fatigue was experienced as bothersome (0 = not at all bothersome; 10 = extremely bothersome) on a 5\" x 8\" card
• Other measures: Pain, nausea, anxiety

• Mean fatigue improved from 4.7–2.7, which is a 40.7% reduction.
• When patients with a fatigue score of more than 4 were included, fatigue decreased from a mean of 6.6 (SD = 1.8) to a mean of 3.8 (SD = 2.6).
• Effects were smaller and less persistent in inpatients.

• No control or randomization was included.
• The sample was not described.
• Fatigue change scores were reported for the total sample at baseline and post-treatment only; however, in a subgroup followed at 12-, 24-, and 48-hours post-massage, the effects of massage on symptom distress were sustained in outpatients. The effects of massage were smaller and less persistent for inpatients, but the researchers noted that inpatients tended to receive shorter massage treatments in less comfortable settings than did outpatients. The relationship between the length of massage treatment and the size and duration of effects is worthy of further study.   
• Weak or cachectic patients may only tolerate foot massage.
• A licensed massage therapist is needed; otherwise, the intervention is inexpensive.

Promising results warrant a controlled trial.

Patients received one of three types of massage therapy and were asked to report their symptoms posttherapy. Massages were provided by 12 licensed massage therapists. Patients were referred by physicians, nurses, or self. Patients received Swedish, light touch, or foot massage according to their preference. On average, sessions lasted 20 minutes for inpatients and 60 minutes for outpatients.

In total, 1,290 patients were included. 

Inpatient and outpatient

Patients reported the level of symptom distress (0–10) on a card prior to and following massage therapy. Comparisons were analyzed by analysis of covariance, with the baseline score as the covariate.

The effect of massage on symptom relief was demonstrated as a positive response with respect to depression.

• Participants were not randomized.
• The information about the study demographics or participants did not include enough detail.
• There was no standard procedure for length of massage or specific type of session. Patients had a choice of three techniques.
• Patients were referred to massage therapy, including self-referral. Self-referral may skew the posttherapy reports because patients expect a benefit.
• No standardized assessment tool was used to measure the results because symptoms were rated on a card.
• There was no way to differentiate which of the massage techniques was the most beneficial.

Patients with cancer received light touch, Swedish, or foot massage. No control group was included.

• The study consisted of 1,290 participants. Of these, 1,255 reported on the nausea question.
• Researchers were unable to ascertain which patients were receiving chemotherapy.
• Patients were self-referred or referred by a physician.

The study was conducted in Inpatient and outpatient settings.

A visual analog scale (VAS) was used to measure nausea and vomiting, pain, fatigue, stress, anxiety, and depression.

Just more than half (51%) experienced a decrease in nausea.

A risk of bias exists for nontraditional treatment.

To describe reported incidence and triggering factors related to development of lymphedema in patients with lymphedema

Questionnaires were sent to 1,020 patients with lymphedema. The names were taken from the Lymphedema Association of Australia. The questionnaire asked about many aspects of their disease. One of the questions was “What triggered your lymphedema?\" Answer choices were infection, insect bite, plane flight, burn, other, or unknown.

Questionnaires were sent to 1,020 patients with lymphedema. A total of 749 responded to the survey, and 531 of these answered the question about what triggered the lymphedema. Responses were as follows: 41 had the condition since birth, 163 had postmastectomy lymphedemas, 136 had primary and 191 had secondary leg lymphedemas. Of those who did not have the condition since birth (n = 490), 27 claimed that it started during an aircraft flight (15 legs and 12 arms). In addition, flying was the identified cause of existing lymphedema to permanently worsen in 23 arms and 44 legs.

Fifty-two patients with advanced colorectal cancer who were treated with a bimonthly oxaliplatin-based regimen were randomized to receive glutathione (GSH) (1,500 mg/m² over a 15-minute infusion period before oxaliplatin) or normal saline solution. Chemotherapy regimen was given as follows: oxaliplatin 100 mg/m² on day 1 concurrent with leucovorin 250 mg/m² followed by 5-FU 1,500 mg/m² per day for two consecutive days every two weeks. GSH was administered at a dose of 1,500 mg/m² in 100 ml of normal saline over 15 minutes immediately before each oxaliplatin administration. The placebo-randomized patients received normal saline. Disease response was assessed after four cycles of therapy. Those with responsive or stable disease received four additional cycles of treatment.

• Fifty-two patients with histologically verified advanced colorectal carcinoma were randomized to receive combination chemotherapy; 26 with and 26 without GSH.
• Patients were excluded if they had established clinical neuropathy, diabetes, alcoholic disease, other neurologic disease or brain involvement.
• Those who received vitamin B1, B6, or B12 supplements also were excluded.

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

• A neurologic examination, including measures of strength and reflexes, assessment of neurologic symptoms, position and vibratory sensation, and neurophysiologic evaluations of sural nerves were conducted at baseline, 4, 8, and 12 cycles of chemotherapy.
• The presence of signs and symptoms of peripheral nervous system involvement and the assessment of position and vibratory sensations also was performed.
• Neurotoxicity was expressed according to National Cancer Institute Common Terminology Criteria for Adverse Events.
• Neurophysiologic evaluation of sensory nerve conduction in the sural nerves was performed by the same examiners who were blinded to the group affiliation.

At baseline, no patients suffered from clinical neuropathy in either arm. At the time of second the neurologic exam (four cycles) seven patients had clinical neuropathy in the GSH arm and 11 in the placebo arm. After eight cycles of chemotherapy, nine patients had clinical neuropathy in the GSH arm compared with 15 patients in the placebo arm with an incidence of moderate to severe (grade 2–4) clinical neurotoxicity present in 11 of 19 assessable patients in the placebo arm, as compared to 2 of 21 assessable patients in GSH arm. No grade 3–4 neurotoxicity was present in GSH arm while grade 3–4 neurotoxicity was reported in five patients in placebo arm. Only 18 patients received 12 cycles of chemotherapy, 10 in the GSH arm and 8 in the placebo arm. Grade 2–3 neurotoxicity was observed in three patients in GSH arm and eight patients in the placebo arm.

The study was performed on patients who had received preliminary date on a small number of patients with no true control group.

Fifty patients with advanced gastric cancer were randomized to receive either 1.5 g/m² GSH in 1 L of normal saline or normal saline 1 L as a placebo infusion given over 15 minutes before cisplatin-based chemotherapy. GSH also was given by intramuscular injection on days 2 and 5. One cycle consisted of nine weekly treatments. Patients who showed responsive or stable disease received an additional six weeks of therapy.

• Fifty patients with advanced gastric cancer; 25 received GSH treatment and 25 received placebo infusions of normal saline.
• Sample size was determined to detect a 40% difference in the occurrence of grade 1–4 (World Health Organization [WHO] scale) neurotoxicity between the two treatment arms.
• Exclusion criteria includes previous chemotherapy, established clinical neuropathy, diabetes, alcoholic disease, brain involvement, or use of vitamins B1, B6, or B12.

The study had a randomized, placebo-controlled clinical trial design.

• Complete neurologic examination (strength, deep tendon reflexes, symptoms of peripheral nervous system involvement, position, and vibratory sensation); neurophysiologic assessment of the medial, ulnar; and sural nerves also were performed.
• Toxicity scores (using the WHO criteria) were evaluated weekly by the same examiner who was blinded to treatment group assignment.

Seven patients in the placebo group were unable to complete the study (six with progressive disease and one from grade 3 neurotoxicity). Only one patient in the GSH group was not able to complete the study. At nine weeks, no patients who received GSH had clinical evidence of neuropathy, compared to16 patients (66%) in the placebo-control group. After 15 weeks, 4 of 24 (17%) patients in the GSH arm showed clinical evidence of neurotoxicity compared to 16 (88%) in the placebo-control group. Most common symptoms included distal parasthesias and numbness in legs, decreased sense of vibration, and reduced or absent deep reflexes. No changes in mean latency and sensory amplitude potentials were noted in the group that received GSH but were significantly affected at 9 and 15 weeks in the control group. No patients reported ototoxicity.

• The study is almost 20 years old.
• Well-described methods and measures recorded higher than expected levels of neurotoxicity in the control arm, but could be from specific attention to the symptom.
• This study did not examine potential delayed toxicity. This could lead to an inaccurate conclusion about the benefits of GSH if it delays rather than prevents toxicity.