The purpose of the study was to demonstrate the activity and safety of XM02 compared to filgrastim for the prevention of chemotherapy-induced neutropenia in patients with non-Hodgkin lymphoma.

Patients randomized in a 2:1 ratio of XM02 to filgrastim for the first cycle of chemotherapy (CHOP or R-CHOP [rituximab added per national guidelines and physician discretion]). All patients received XM02 in subsequent cycles, with a maximum of six cycles; three weeks per cycle. Subcutaneous injections given daily (5 mg/kg per day) for at least five days and a maximum of 14 days. Drug stopped with the absolute neutrophil count (ANC) of  10 x 10⁹/L or greater after nadir was reached (blood samples to evaluate ANC taken within 24 hours prior to start of chemotherapy and then daily from day 2 on in the first cycle and day 5 on in cycles 2–6 until day 15 or until ANC reached greater than 2.0 x10⁹/L). Body temperature measured daily until day 15 or until ANC reached greater than 2.0 x10⁹/L.

• 92 total patients were in the sample.
• Age ranged from 18-83 years.
• For women, were in the XM02 group and 12 were in the filgrastim group.
• For men, 31 were in the XM02 group and 17 were in the filgrastim group.
• Patients had aggressive NHL, defined as diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, follicular lymphoma grade 3, or anaplastic large cell lymphoma.
• Eligible patients had to be chemotherapy-naïve, have a life expectancy of six months or longer, an international prognostic index score of 3 or lower, an ANC greater than 15 x 10⁹/L, a platelet count greater than 100 x 10⁹/L, and adequate hepatic, cardiac, and renal function for the chemotherapy regimen.

Multiple inpatient and outpatient settings

Active treatment

Phase III, randomized, controlled trial

• Duration of severe neutropenia (DSN)    
• Febrile neutropenia    
• ANC
• Adverse events: musculoskeletal and connective tissue disorders (bone pain, arthralgia, back pain, musculoskeletal pain, jaw pain); general disorders and administration site conditions (pyrexia, fatigue, flu like illness); gastrointestinal (diarrhea); nervous system (HA), vascular (hot flush); and blood and lymphatic (anemia)
• Pharmacokinetics
   

XM02 was found to be pharmacokinetically similar to filgrastim and not statistically significantly different from filgrastim for febrile neutropenia (FN) in cycle 1 (11.1% for XM02 and 20.7% for filgrastim). ANC values in both groups reached a maximum at day 4 and decreased to a nadir on day 9 followed by an increase reaching a maximum on day 11, with a return to day 1 mean values reached on day 21 (similar to other filgrastim studies). Drug-related adverse events were not statistically different between XM02 and filgrastim.

The administration of G-CSFs for the prevention of chemotherapy-induced neutropenia and related adverse events has been proven effective in many trials. Use of XM02 has similar pharmacokinetics, safety, and efficacy compared to the established filgrastim. Other studies show greater efficacy with pegylated filgrastim that requires less dosing than the daily doses of filgrastim. The use of XM02 instead of filgrastrim does not seem favorable based on these results.

• Small sample size (less than 100 participants)
• This study was sponsored and funded by BioGeneriX AG, the manufacturer of XM02.
• Filgrastim was only compared to XM02 in the first chemotherapy cycle, then all patients received XM02; yet the results evaluated outcomes throughout the duration of all chemotherapy doses.
   

Based on this study alone, nurses can be aware that XM02 for patients 18 and older with aggressive NHL for the risk reduction of neutropenia and related adverse outcomes will be similarly effective to filgrastrim.

DATABASES USED: MEDLINE (1966–1996); the reference lists of retrieved articles also were reviewed.

• FINAL NUMBER STUDIES INCLUDED = 18 RCTs
• TOTAL PATIENTS INCLUDED IN REVIEW: 707
• KEY SAMPLE CHARACTERISTICS: Patients were undergoing chemotherapy for malignancy (primarily hematologic malignancies). Quinolone prophylaxis was compared with placebo (nine trials) or trimethoprim/sulfamethoxazole (nine trials). The article did not state whether patients received granulocyte colony-stimulating factors.

Without prophylaxis

• 82% of patients developed fever.
• 25% of patients developed gram-negative infections.
• 23% of patients developed gram-positive infections.
• 55% of patients developed any infection.

Compared with no prophylaxis, quinolone prophylaxis decreased the risk of

• Gram-negative infections by 79%
• Gram-negative bacteremia by 77%
• Microbiologically documented infections by 35%
• Total infections by 46%
• Fever by 15%.

Compared with trimethoprim/sulfamethoxazole prophylaxis, quinolone prophylaxis decreased the risk of

• Gram-negative infections by 70%
• Gram-negative bacteremia by 68%
• Microbiologically documented infections by 28%
• Total infections by 17%.

Quinolone prophylaxis did not affect the rate of

• Gram-positive infection or bacteremia
• Fungal infection
• Clinically documented infection
• Infection-related death.

The rate of quinolone-resistant gram-negative infections was 3.0%, and the rate of quinolone-resistant gram-positive infections was 9.4% among patients who received quinolone prophylaxis, but no data were provided regarding the rate of quinolone-resistant infections among the control group. Therefore, the effect of quinolone prophylaxis on the rate of quinolone-resistant infections is unknown.

To evaluate the effectiveness of pyridoxine to prevent palmar plantar erythrodysesthis (PPE) in patients receiving pegylated liposomal doxorubicin (PLD) (Doxil^®) in patients with advanced solid tumors

Patients were receiving a treatment regimen consisting of PLD (doses escalating in dose level 1–4 from 20–40 mg/m² every 21 days), in combination with paclitaxel (90 mg/m² in dose level 1, 135 mg/m² in dose levels 2–4), and cisplatin (60 mg/m²). All patients were given oral pyridoxine 50 mg three times daily on days 2–21 of each cycle. The study occurred from May 1997–March 2000.

• N = 23
• KEY DISEASE CHARACTERISTICS: Patients with advanced solid tumors
• OTHER KEY SAMPLE CHARACTERISTICS: Receiving PLD, paclitaxel, and cisplatin

• LOCATION: Department of Medicine, University of Chicago, Chicago, IL

• Phase I study

• National Cancer Institute Common Toxicity Criteria version 1.0

No episodes of grade 3–4 (dose-limiting) PPE were reported. Grade 1–2 PPE occurred in 4 of 18 patients (22%) who received more than two cycles of chemotherapy, resulting in no treatment-related interruptions or dose reductions.

Incidence of PPE was low in patients who received pyridoxine prophylactically and Doxil 20–40 mg/m².

• Small sample size
• This was not a randomized controlled trial.

To determine if the addition of midazolam and diphenhydramine to granisetron plus dexamethasone reduces chemotherapy-induced nausea and vomiting (CINV) in children receiving highly emetogenic chemotherapy (HEC)

Children were randomly assigned to receive one of two regimens on alternating cycles of chemotherapy. The first regimen was granisetron 0.04 mg/kg plus dexamethasone 0.2 mg/kg, and the second regimen was midazolam 0.04 mg/kg, diphenhydramine 2.5 mg/kg, and granisetron 0.04 mg/kg plus dexamethasone 0.2 mg/kg. The intervention drugs were diluted in 100 ml of 5% dextrose and administered via infusion one hour prior to chemotherapy. Patients and nurses tracked CINV symptoms in a daily diary, and CINV symptoms were assessed on day 1 (acute phase) and days 2–5 (delayed phase) of the chemotherapy cycle.

• N = 23  
• MEDIAN AGE = 7 years (range = 1–16 years)
• MALES: 56.5%, FEMALES: 43.5%
• KEY DISEASE CHARACTERISTICS: Neuroblastoma, germ cell tumor, rhabdomyosarcoma, Ewing's sarcoma, hepatoblastoma, adrenocortical carcinoma 
• OTHER KEY SAMPLE CHARACTERISTICS: Pediatric; all patients received cisplatin 

• SITE: Single-site    
• SETTING TYPE: Not specified    
• LOCATION: India

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Randomized, controlled trial

• Complete response = no nausea and vomiting
• Partial response = one to two emetic episodes but no rescue therapy
• No response = more than three emetic episodes or rescue therapy.

In the acute phase, of the children who received the first regimen, 84.4% had a complete response rate compared to 90.3% who received the second regimen (95% CI: 0.78, 96, p = 0.37). Of the children who received regimen 1, 15.5% had a partial response, and 9.6% of those who received regimen 2 had a partial response. In the delayed phase, 64.4% of patients who received regimen 1 had a complete response compared to 51.6% who received regimen 2. Partial response rates were observed in 31.1% of patients in regimen 1 and 41.9% in regimen 2. Failure rates were 4.4% in regimen 1 and 6.45% in regimen 2. Children receiving regimen 2 had more adverse events including hypotension (two patients) and marked sedation (four patients).

The addition of midazolam and diphenhydramine does not improve CINV in children receiving HEC.

• Small sample (< 30)
• Risk of bias (no blinding) 
• Measurement/methods not well described

The addition of midazolam and diphenhydramine does not improve CINV associated with HEC in pediatric patients, and the addition increased the number of adverse side effects children experienced. Nurses should consider different interventions to help control CINV in pediatric patients who are receiving HEC.

To examine 18- and 24-month outcomes for patients who participated in the Alleviating Depression Among Patients with Cancer (ADAPt-C) clinical trial, whose aim was to improve access to culturally adapted depression care among low-income, predominantly Hispanic women with cancer

The usual-care group received standard oncology care for patients with depression. Oncologists were free to prescribe antidepressants or mental health care to both groups, and patients were free to use community mental health services. The intervention is adapted from the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) intervention, which provided collaborative intervention focused on problem solving, health navigation, personalized treatment and monitoring, assessment, and follow-up and education by a specialist. Follow-up occurred by telephone monthly.

• N = 210 (patients who completed 24-month assessment, 44% of initial study).
• Mean patient age was 48.7 years (SD = 12.9 years).
• Males, 11%; females, 89%.
• Of all patients in the study, 93% were Hispanic; 75% had been in the United States for more than 10 years.
• Baseline data: 64% of cancers were gynecologic or breast cancers; 28%, stage III or IV recurrent cancer.
• Mean depression score at baseline was 12.52 (SD = 3.36).
• Included patients had received a cancer diagnosis at least 90 days prior to baseline and met criteria for having symptoms of depression as stated in eligibility.
• Patients were excluded if they had suicidal ideation, had a life expectancy of fewer than six months, reported scores greater than or equal to 8 on the Alcohol Use Disorders Identification Test, had recently used lithium or antipsychotic medication, had a score of equal to or less than 2 on the Karnofsky Performance Status Score, or were unable to speak English or Spanish. 

• Multisite
• Outpatient
• California and southern Florida

• Phase of care: long-term follow-up
• Applications: late effects and survivorship
   

Randomized control trial, longitudinal 

• Patient Health Questionnaire-9 (PHQ-9)
• Functional Assessment of Cancer Therapy Scale
   

• The number of reports of receiving treatment for depression declined over time; however, reports of treatment were more numerous in the intervention group. At 12 months, researchers found significant differences (p < 0.001) between groups in regard to use of antidepressant medication, with the intervention group reporting greater use of antidepressant medications.
• The intervention group reported greater use of counseling at 12 months (p < 0.001) and 18 months (p = 0.001), than did the other group.
• The number of reports of having had any depression treatment was significantly different in the intervention group at 12 months (p < 0.001) and 18 months (p = 0.001).
• The intervention group had a 46% decrease in PHQ-9 scores; the usual-care group had a 32% decrease, which was a significant decrease (p = 0.02). The intervention group was significantly more likely to have decreased its PHQ-9 score by 5 points since baseline at 12, 18, and 24 months (p = 0.01, p =0.03, p = 0.02, respectively).

The effectiveness of the psychoeducational components of the intervention is unclear because patients in the experimental group also used antidepressants to a greater degree and received more counseling than did patients in the other group. Evidence does support the conclusion that, in the intervention group, management of depression improved.

• The study had no appropriate attentional control condition.
• The control group had no attention control, a fact that limits interpretation of between-group differences. 
• This was a complex and multifaceted intervention; therefore, knowing which component of the intervention had the greatest influence is difficult.
   

Collaborative supportive care with symptom monitoring, support, and follow-up can help patients with depression improve their outcomes. Ongoing monitoring and involvement to address depression in patients appears to result in more treatment of depression. Future work is needed to understand which component of this intervention is most effective.

To perform intent-to-treat meta-analyses on pooled data, to compare the effect of collaborative multidisciplinary care on depression in older adults to that received by younger adults

• This study did not involve database searches; authors analyzed three randomized trials. Search keywords were not provided.
• Authors selected trials with similar designs (i.e., similar intervention and measurements).
• The study provided no information about trial exclusion. One can note, however, that each of the three trials excluded participants for these factors: acute suicidality, high alcohol use scores, recent use of lithium or antipsychotic medications, life expectancy of fewer than six months, and significant cognitive impairment.
   

• Evaluation involved a no-scoring system applied to three clinical trials. Authors examined reanalyzed pooled data from the trials. The outcome measures were
  • Treatment responses (where a 50% reduction in the Patient Health Questionnaire-9 (PHQ-9) score from baseline was considered a clinically meaningful improvement in symptoms of depression).
  • Major depression (PHQ-9 ≥ 10).
  • Composite scores of quality-of-life subscales (the Short-Form Health Survey).
  • Health care utilization.
• The three studies employed similar collaborative care as an intervention. The intervention included antidepressant medication, problem-solving therapy, and by-telephone symptom monitoring and relapse prevention by telephone over 12 months. The intervention incorporated personalized multidiscipline collaborative care based on the structured algorithm for stepped care. For example, a clinical specialist in depression communicated with an antidepressant prescriber in regard to a patient’s medication.
• The control group in all three studies received enhanced usual care. The usual care included standard health system care, patient- and family-focused educational pamphlets on depression, and community resources. However, usual care in the studies differed slightly as the result of differences in setting.
• In all three studies, data were collected at baseline, 6 or 8 months, and 12 months.
   

• Samples from the three randomized controlled trials consisted of 1,081 patients with major depressive symptoms and comorbid illness. When combining data, authors excluded patients with dysthymia alone or patients with no depression.
• Sample range across studies:
  • Study 1: cancer trial, n = 472, age 18 and older
  • Study 2: diabetes trial, n = 387, age 18 and older
  • Study 3: homecare trial, n = 311, age 65 and older.
• Key sample characteristics:
  • Total sample: age 60 and older, n = 440; age 18–59, n = 641.       
  • Patients had diverse multiple diseases (cancer, diabetes, hypertension, heart disease, kidney disease, etc.).
  • Sites were oncology and primary care safety-net clinics and diverse home healthcare programs.

• Phase of care: long-term follow-up
• Clinical applications: late effects and survivorship, eldercare

• Comparing patients ≥ 60 years to patients 18–59 years revealed no significant differences with respect to reducing depression symptoms (p = 0.18–0.58) or improving quality of life (t = 1.86, df = 669, p = 0.07 for physical functioning at 12 months, and p = 0.23–0.99 for all others).
• At six months in both age groups, intervention patients had significantly higher rates of a 50% reduction of the PHQ-9 score (older patients: Wald chi [df = 1] = 4.82, p = 0.03; younger patients: Wald chi [df = 1] = 6.47, p = 0.02) and  a greater reduction in major depression rates (older patients: Wald chi [df = 1] = 7.72, p = 0.01; younger patients: Wald chi [df = 1] = 4.0, p = 0.05) than did patients receiving enhanced usual care.
• There was no significant age-group differences in treatment type or intensity.

Study findings indicate that collaborative depression care in individuals with diverse comorbid illness is as effective in reducing depression in older patients as it is in younger patients, including those in low-income, minority classifications.

This phase 3 trial was designed to compare an emulsion containing trolamine against usual supportive care within each participating institution.

Patients were randomly assigned to one of three treatment arms:  (a) prophylactic trolamine emulsion, (b) interventional trolamine emulsion, and (c) declared institutional preference.

In both trolamine arms, trolamine was applied at four-hour intervals. Patients were instructed to maintain at least four hours between trolamine and radiation therapy (RT).

Trolamine use was discontinued immediately if an allergic reaction occurred or if grade 3 dermatitis was reported in any area larger than 1.5 cm of confluent desquamation or bleeding in the treatment area.

• The sample was comprised of 547 patients (79% male).
• Mean age was 59 years.
• Patients had head and neck cancer.
• Approximately 80% of the patients received an RT dose greater than 60 Gy.
• Of the patients, 53% on study received combined-modality treatment.

Fifty-one institutions in various states in the United States

The study was a randomized, controlled trial.

• The primary outcome was the reduction in grade 2 or higher skin toxicity, per National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2 and the ONS toxicity scoring tool.
• Secondary outcomes included patient-reported quality of life (QOL).
• Skin assessments and QOL forms were completed before RT, weekly during RT, and weekly for four weeks after RT.
• The Spitzer QOL Index (SQOLI) and the Head and Neck Radiotherapy Questionnaire (HNRQ) were used to measure QOL. A higher score indicated greater toxicity and poorer QOL.

• The rates of grade 2 or higher radiodermatitis were 79%, 77%, and 79% in the prophylactic, interventional, and institutional preference arms, respectively.
• Rates of grade 3 or 4 dermatitis did not differ, with rates of 25%, 25%, and 23% in the three arms, respectively.
• Confluent moist desquamation was observed in 7%, 10%, and 8% of patients in the prophylactic, interventional, and institutional preference arms, respectively.
• Ulceration, hemorrhage, and necrosis were experienced in 2%, 3%, and 1% of the patients in the three arms, respectively.
• The ONS toxicity score reported a small to moderate amount of moist desquamation in 31%, 28%, and 34% of patients in the prophylactic, interventional, and institutional preference arms, respectively.
• No significant differences were found in QOL.
• Fourteen products were reported as standard of care. The most commonly used product was Aquaphor, which was the institutional preference for 39% of the patients.
• A slightly higher rate of treatment breaks was reported in the institutional arm than in both trolamine arms for current and former smokers, but the breaks on average were shorter.

The results demonstrate no advantage for the use of trolamine in reducing the incidence of grade 2 or higher radiodermatitis or improving patient-reported QOL.

• Absence of patient diaries to record compliance with application directions, the timing and number of applications, and the full amount of product used was a limitation. The product log for this trial was a record of the number of tubes supplied to each participant.
• The study was not blinded or placebo-controlled, which introduced the possibility that the skin grading and QOL assessments were subject to reviewer and patient bias.

To determine the effectiveness of Alleviating Depression Among Patients with Cancer (ADAPt-C) collaborative care management for major depression or dysthymia

ADAPt-C is collaborative care management developed for low-income and minority patients. The control group received enhanced usual care (EUC). Data collection occurred at baseline, 6 months, and 12 months. The intervention involved semistructured assessment and patient and family education, navigation assistance, behavioral therapy components in weekly sessions, and patient homework. After treatment initiation, patients received monthly telephone contact for up to 12 months, for maintenance and relapse prevention. Medication was used as clinically indicated for psychiatric symptoms. Overall management was based on guidelines, from the National Comprehensive Cancer Care Network, for treatment of depression in cancer patients. 

• N = 472 participants (242 in the intervention group  and 230 in the control group).
• Of participants, 49.4% was age 50 or older.
• Female: 84.5%; male: 15.5%.
• Participants had diverse cancer types at a variety of stages. Most participants (42.6%) had gynecologic cancer.
• Adult patients showed evidence of depression or dysthymia after cancer diagnosis.
• Of all participants, 87.9% were Hispanic.
• Intervention and control groups differed at baseline in regard to emotional well-being and quality of life. Researchers noted lower well-being in the intervention group.
• The two groups differed in regard to percentage of foreign-born participants. The greater percentage was in the intervention group (p = 0.04).

• Single site
• Outpatient
• Southern California

Active treatment and transition

Prospective, randomized, controlled trial with simple blinding

• Patient Health Questionnaire-9 (PHQ-9) for the diagnosis of major depression and depression severity level
• Functional Assessment of Cancer Therapy-General (FACT-G)
• Medical Outcome Study 12-item Short-Form Health Survey (SF-12) for quality of life
• Brief Pain Inventory (Short Form)

• From baseline to the 12-month follow-up, 63.2% of intervention patients had a 50% or greater reduction in depression symptoms as assessed by the PHQ-9 depression scale. In comparison, 50% of patients in the EUC group had a 50% or greater reduction (p = 0.01).
• Researchers noted five-point reduction in the PHQ-9 score: 72.2% of intervention patients versus 59.7% of EUC (p = 0.02).
• Intervention patients had significantly better quality-of-life outcomes (p < 0.05).
• At the six-month follow-up, researchers found no difference between groups in regard to depression severity.
• Intervention patients experienced greater rates of depression treatment (p < 0.0001).

ADAPt-C collaborative care may be a feasible and effective means of reducing symptoms of depression in some cancer patients.

• The study may have had risks of bias due to large attrition (214 participants, or 45% of participants), lack of control over the type of cancer treatments, and the range of time lapses since treatment.
• The baseline differences in the emotional well-being subscale scores of the FACT-G and SF-12 mental component summary were not adjusted for the main analyses.
• Cost will be involved in training the team members (e.g., a clinical specialist) and in hiring these personnel.

ADAPt-C is a time- and personnel-intensive intervention that requires significant commitment on the part of the patient.

Researchers compared a hypnosis intervention (five weekly sessions) or no treatment.

Sixty female breast cancer survivors with hot flashes were enrolled.  Eligible patients had to have a history of primary breast cancer without evidence of detectable disease and 14 or more weekly hot flashes for at least one month.

Participants were randomly assigned to treatment with hypnosis or no treatment.

The instrument was the Hot Flash Related Daily Interference Scale.

Fifty-one randomly assigned women completed the study. By the end of the treatment period, hot flash scores (frequency and average severity) decreased 68% from baseline to end point in the hypnosis arm (p ≤ 001). Significant improvements in self-reported anxiety, depression, interference of hot flashes on daily activities, and sleep were observed for patients who received the hypnosis intervention (p ≤ .005) in comparison to the no treatment control group.

Study limitations included:

• Five weeks duration
• No physiologic monitoring of hot flashes
• No long-term follow-up

The study looked at the effectiveness of hypnosis in treating hot flashes in breast cancer survivors.

Each participant received four weekly sessions of hypnosis using a standardized transcript and was instructed in self-hypnosis.

Sixteen breast cancer survivors were enrolled.

This was a pilot study.

Participants kept daily diaries of the frequency and severity of their hot flashes. They also completed baseline and post-treatment ratings of the degree to which hot flashes interfered with daily activities and QOL using the Hot Flash-Related Daily Interference Scale.

Results indicated a 59% decrease in total daily hot flashes and a 70% decrease in weekly hot flash scores from the baselines. Participants experienced a significant decrease in the degree to which hot flashes interfered with daily activities for all measures including work, social activities, leisure activities, sleep, mood, concentration, relations with others, sexuality, enjoyment of life, and overall QOL.

This study was limited by its small sample size and the limitations inherent in single group study design. All of the participants expressed interest in hypnosis, which may indicate some selection bias. Because no comparable control group was used, identifying the exact efficacy of hypnosis as a treatment for hot flashes is not possible.