DOI Link: doi: 10.1188/02.ONF.1063-1080

Database searched was MEDLINE (1966–2001). Additional papers were found from reference lists.

Studies were included in the review if they were aimed at prevention, palliation, or reduction of radiation-induced oral mucositis in patients with head and neck cancer.

Studies were excluded if they were not in English.

More than 50 studies were included. Most were randomized, controlled trials; some were pilot or descriptive studies. 

Sample sizes ranged from 10 to more than 200.

Based on the findings of studies conducted to date, no conclusions regarding the agents and their ability to decrease the severity of radiation-induced oral mucositis were possible. Results were inconsistent. The most effective measure to treat radiation-induced mucositis was frequent oral rinsing with a bland mouthwash such as saline or sodium bicarbonate. Consistent oral care, dental care, oral assessment, and standardized oral hygiene were the suggested approaches to managing oral mucositis. Sodium bicarbonate reduces the acidity of the oral fluids immediately; it also dilutes accumulating mucus and discourages yeast colonization.

Findings related to benzydamine were inconsistent. In a trial of chlorhexidine versus benzydamine, patients reported more discomfort with benzydamine and were more likely to discontinue participation in the trial. Chlorhexidine was not effective in reducing the severity of mucositis in three double-blind, placebo-controlled trials. Two trials that examined antimicrobial activity failed to show any significant effects on the suppression of any type of oral flora using chlorhexidine.

Dose variations in granulocyte macrophage colony-stimulating factor (subcutaneous) trials make it impossible to determine whether this agent has a role in the radiation setting.

Four studies investigated the effectiveness of using topical antibiotics with a more specific spectrum for gram-negative bacteria and yeast. Two placebo-controlled, randomized clinical trials, both with fewer than 100 patients, and one case-controlled study investigated the efficacy of amphotericin B (polymyxis E, tobramycin, and amphotericin B [PTA] lozenge) to reduce the severity of radiation-induced mucositis. One study examined tetracaine and antibiotics. Additional work is warranted to determine the effects of the PTA lozenge on mucositis severity, pain severity, and dysphagia. Results for the trial were promising; however, conclusions cannot be drawn because only one study examined tetracaine.

Additional investigation of immunoglobulin and povidone-iodine are recommended.

To investigate how limited hydration in the first part of retropubic radical prostatectomy (RRP) affects the volume of intra-operative total blood loss to offer a definite hydration method during RRP

The experimental group underwent a RRP performed by the same surgeon. Eight anesthesiologists took part in the study, with each anesthesiologist completing a single case. During the first two hours of the procedure, the amount of IV fluids the patient received was limited to 1,500 ml. The control group also had RRP performed by the same surgeon; however, there was no definite methods of hydration. The two groups were matched in regard to age, serum prostate-specific antigen score, specimen weight, body mass index, performance of neoadjuvant hormonal therapy, and total IV infusion volume. No patients in either group received nerve-sparing surgery. Measurements included blood loss, IV infusion volume in the first two hours of surgery, total infusion volume, and pre- and postoperative hematocrit value.

• N = 37
• AGE = 51–79 years
• MEDIAN AGE = 66.5 years
• MALES: 100%          
• KEY DISEASE CHARACTERISTICS: Both the control and experimental groups were diagnosed with prostate cancer with elevated PSA scores. Gleason’s ranged from 6–9, with 40% of patients receiving neoadjuvant hormonal therapy prior to surgery. 
• OTHER KEY SAMPLE CHARACTERISTICS: None

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Akashi Municipal Hospital

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care 

• Controlled trial

• Blood loss 
• IV infusion volume in the first two hours of surgery
• Total infusion volume 
• Pre- and postoperative hematocrit value

The study demonstrated that patients receiving limited hydration remained normotensive during the first two hours of their RRP (p = 0.0343). The experiment group, those receiving limited hydration, as compared to those without IV infusion limits, also demonstrated a significant difference in overall blood loss (p = -0.0301). However, the authors further concluded that patients receiving limited hydration did not experience any adverse effects from the limited hydration (i.e., dehydration). There was no evidence in the article to support this conclusion other than one blood pressure writing during the first two hours of surgery.

Use of limited hydration in RRP during the first two hours of surgery is shown to significantly reduce blood loss (p = 0.0301). However, further studies are needed to determine if limiting hydration causes any adverse effects from the effects of dehydration.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Findings not generalizable
• Differences in physique and shape of pelvis between Japanese and American men limits generalizability to American population; different methodologies of hydration should be considered.

The fluid balance assessment was accurate. Nurses should educate patients on surgery and the amount of bleeding to expect with the role of hydration in reducing bleeding.

DOI Link: doi:10.1080/07347332.2010.516811

To compare a coaching intervention that uses a prompt sheet with usual care to improve cancer provider and survivor communication about survivor worries

The study involved a telephone coaching session using a prompt sheet and a nurse guiding a participant in prioritizing concerns to be addressed at an upcoming oncologist visit.

• The sample was comprised of 44 survivors with breast cancer (100% female).
• Mean survivor age was 44.1 years.
• Mean age at diagnosis was 38.5 years; 20% were diagnosed at stage I, 53% at stage II, and 27% at stage III.
• Mean time since diagnosis was 5.5 years.
• All were disease-free at the time of enrollment.
• All survivors had undergone chemotherapy.
• The sample was 95% white.

• Outpatient setting
• University cancer center in Indiana

• Long-term follow-up phase
• Late effects/survivorship

A randomized controlled trial design was used.

• Breast Cancer Self-Efficacy Scale: 14-item scale with a five-point Likert-type response developed for the study (Cronbach’s alpha = 0.84, content validity confirmed by 12 breast cancer survivors, 4 clinical experts, and 2 cancer research experts)
• Spielberger State-Trait Anxiety Inventory (STAI)–State subscale
• Center for Epidemiological Studies Depression Scale (CES-D)
• Concerns About Recurrence Scale (CARS)

Most concerns centered around current symptoms, long-term effects of treatment, and recurrence of cancer. The prompt sheet and coaching did not have a significant effect on depression, anxiety, or worries. Survivor questions communicated worry about symptoms and long-term side effects experienced by young breast cancer survivors.

Self-efficacy may be a significant predictor of survivors’ state of anxiety and depression.

• Study findings are limited by sample demographics (mostly white, highly educated women).
• The study had no blinding or attentional control.
• The study’s lack of direct observation of communication between the survivor and oncologist limits the understanding of how the prompt sheet changed and/or facilitated communication.

This type of intervention may help survivors to think about their concerns prior to an office visit and organize their thoughts for the visit so that priority issues can be addressed. Whether this has an impact on outcomes has not been supported. Findings suggest that self-efficacy is predictive of role concerns and emotional outcomes such as state anxiety and depression.

DOI Link: doi: 10.1097/CAD.0b013e3283610b5d

To compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens

Fifteen centers enrolled 337 chemotherapy-naïve patients with cancer with normal bone marrow function. All patients were randomized into AOB and BOA arms and received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 mg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 lg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). In the AOB arm, 173 patients were enrolled and 155 completed the two cycles. In the BOA arm, 164 patients were enrolled and 142 completed the two cycles. Efficacy and safety parameters were recorded. The primary endpoint was the rate of protection against grade 4 neutropenia after chemotherapy (defined as the rate at which the absolute neutrophil count [ANC] remained greater than 0.5 x 10⁹/L throughout the entire cycle).

• N = 337  
• AGE = 18–70 years
• MALES: 68 (AOB), 60 (BOA); FEMALES: 101 (AOB), 97(BOA)
• KEY DISEASE CHARACTERISTICS: Primarily breast, non-small cell lung cancer, and non-Hodgkin lymphoma; study arms essentially equal, except the BOA arm did enroll two patients with head and neck cancer; stage of disease was split equally throughout both arms
• OTHER KEY SAMPLE CHARACTERISTICS: The groups were well matched with respect to demographics, history of disease, disease severity, and ANC at baseline. The median age of patients in the study was 50 years, and almost 40% of the patients were men. Breast cancer was the most common histology. About 50% of the enrolled patients previously had undergone surgery.

• SITE: Multi-site   
• SETTING TYPE: Outpatient   
• LOCATION: Republic of China

• SITE: Multi-site   
• SETTING TYPE: Outpatient   
• LOCATION: Republic of China

• Multi-center, randomized, open-label, crossover, noninferiority study

Blood samples were collected for complete blood counts with differential on days 0, 3, 5, 7, 9, 11, 13, 17, and 21 of each cycle. The primary efficacy endpoint was the rate of protection from grade 4 neutropenia (ANC remains greater than 0.5 through the entire cycle) after chemotherapy. The secondary efficacy endpoints included the rate of grade 3/4 neutropenia, time to neutrophil recovery (defined as the time from chemotherapy administration until the ANC increased to 2.0 [after the expected nadir]), incidence of febrile neutropenia (ANC less than 0.5 and axillary temperature higher than 38.1°C), incidence of antibiotic administration, and ANC profile.

Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. In cycle 1, the rates of protection were 89.7% (pegylated filgrastim) and 89.5% (filgrastim). In cycle 2, no episodes of grade 4 neutropenia occurred. In subgroup analysis according to chemotherapy regimens, the protective rates of pegylated filgrastim did not differ significantly from the protective rates of filgrastim.

This trial provides direct evidence that pegylated filgrastim is comparable to filgrastim in efficacy and safety when administered in support for commonly used, standard-dose, mild-to-moderate myelosuppressive chemotherapy regimens. In addition, the single injection per cycle may lead to increased patient satisfaction and compliance.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Other limitations/explanation: Not clear that the sample was at risk for neutropenia

Increased use of pegylated filgrastim across solid tumor types with mild-to-moderate myelosuppressive chemotherapy regimens. The lower frequency of visits may lead to increased emergency department visits for toxicities that normally would be caught at the daily injection visits. Education will be key in this patient population. For some patients, avoidance of daily injections may be important.

DOI Link: doi: 10.18632/oncotarget.8255

STUDY PURPOSE: To identify the best triple drug antiemetic regimen for cisplatin-induced nausea and vomiting

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: Not stated

INCLUSION CRITERIA: All were double-blind randomized controlled trials.

EXCLUSION CRITERIA: Not cisplatin-based therapy, no triple-drug regimen used, non-English language

• FINAL NUMBER STUDIES INCLUDED = 10
• TOTAL PATIENTS INCLUDED IN REVIEW = 7,317
• SAMPLE RANGE ACROSS STUDIES: 174–2,322 patients
• KEY SAMPLE CHARACTERISTICS: All were receiving cisplatin-based chemotherapy.

PHASE OF CARE: Active antitumor treatment

Pairwise meta-analysis was done to rank treatments for effectiveness in terms of complete response (CR) rate. Ranking for best results was: (a) netupitant, palonosetron, and dexamethasone (NEPA); (b) fosaprepitant, ondansetron, and dexamethasone; (c) palonosetron and dexamethasone; (d) fosaprepitant, granisetron, and dexamethasone. However, comparisons did not reach statistical significance. NEPA also ranked highest in percentage of cases with no nausea. The regimen of aprepitant, granisetron, and dexamethasone ranked highest in the side effect of constipation. The regimen of rolapitant, ondansetron, and dexamethasone ranked highest for delayed nausea control and fewest side effects. No significant differences existed across regimens in side effects.

Findings suggest that triple drug regimens, including NEPA, may be most effective in chemotherapy-induced nausea and vomiting (CINV) prevention and the prevention of delayed nausea, though actual differences across all triple drug regimens were not statistically significant.

The authors noted that some evidence reveals that the efficacy of various triple drug regimens may depend upon the tumor type rather than the antiemetic regimen. In general, all triple drug antiemetic regimens are shown to be effective for CINV management, and variation across regimens exists regarding their efficacy for nausea and response in the delayed phase, in particular. Further research is needed to identify comparative effectiveness for various regimens with analysis by tumor type as well as type of chemotherapy. In practice, given potential differences in effect, regimens for individual patients should be planned according to individual patient responses and risks.

To compare the efficacy and safety of two different 5-HT₃ receptor antagonists

Patients were randomized to one of two groups. In the first group, patients received ramosetron for prevention of chemotherapy-induced nausea and vomiting (CINV) in cycle 1 of highly emetogenic chemotherapy (HEC) and then ondansetron in cycle 2. Patients in group 2 received ondansetron first, followed by ramosetron.

The study consisted of 50 patients.

The study was conducted in China.

This was a prospective, randomized, crossover trial.

Nausea, emesis, and loss of appetite were assessed, but the authors did not describe how this data was collected or by whom.

No significance was reported for any measure between groups at any time point.

No significant differences were reported between the two groups on any measure at any time point

• The sample size was small.
• The measures were not clear.

DOI Link: doi:10.1007/s00520-011-1295-5

To evaluate whether participation in a problem-solving intervention influences level of caregiver assistance with patient symptoms, caregivers’ depressive symptoms, burden mastery, and caregiver/patient communication at 10 and 16 weeks postparticipation

Caregivers in the dyads assigned to the intervention group received three telephone calls from a master’s-prepared nurse to assist them in assessing and managing patient symptoms. Both the intervention and control groups received written materials on these topics, and control group caregivers received calls from a non-nurse coach who reminded them of applicable content sections of the written materials. Measures were obtained at baseline, 10, and 16 weeks. Both groups received a symptom management toolkit containing written materials on symptom assessment, communication, and symptom management. Intervention group caregivers received three phone calls from a nurse to assist in identifying and managing symptoms; control group caregivers received calls from a non-nurse coach who reinforced the material in the toolkit.
 

• The sample was comprised of 225 caregiver/patient dyads.
• Mean caregiver age was 53.8 years (SD = 12.7) in the intervention arm and 56.1 years (SD = 13.1) in the control arm. Ranges were not reported.
• The intervention arm had 47 males (SD = 41.96) and 65 females (SD = 58.04); the control arm had 43 males (SD = 38.05) and 47 females (SD = 41.96).
• Patients were 40 years or older, without cognitive impairments; were English-language users; had touch-tone telephone service; had stage III or IV solid tumors; were not on hospice; and had a family caregiver.
• Patients had to be actively receiving chemotherapy during the study and report both pain and fatigue within seven days prior to recruitment.
• Patients under the care of a psychiatrist or psychologist were excluded.

• Multisite 
• Home setting
• Telephone intervention

Active antitumor treatment phase

A randomized controlled trial design was used.

• Cancer Symptom Inventory
• Caregiver Symptom Involvement (developed for study)
• Center for Epidemiologic Studies–Depression Scale (CES-D)
• Caregiver Reaction Scale (caregiver burden)
• ENRICH Marital Inventory–Family Communication Subscale
• Pearlin Mastery Scale

The statistically significant effect observed in the study related to a differential effect of depression in the intervention arm at the 10-week time point, where caregivers with lower levels (less than 16 on the CES-D) were twice as likely to provide an intervention for patient symptoms than those with a higher depression score (OR = 1.99, 95% CI = 1.45–2.76). Caregiver self-esteem was also statistically significantly different in the intervention arm (p = 0.04), but the authors noted that in the clinical context, this finding was likely due to chance.

Although no significant differences were noted overall between the nurse-led intervention and the control group, knowledge was gained regarding the impact of caregiver depressive symptoms on the degree of interventions offered to the patient with cancer experiencing symptoms. Future research may focus on tailoring interventions based on dynamic characteristics such as degree of caregiver distress concurrent to increasing patient symptom needs.

The study had risk of bias because the sample was described as primarily Caucasian: The authors cited literature noting variances in caregiver emotional responses by race, which might have implications given the findings associating depressive symptoms and caregiver responsiveness.

The authors speculated that caregivers with higher levels of depressive symptoms may be less able to act on behalf of their family members who are patients. In practice, nurses should assess whether caregiver distress may impact outcomes such as medication adherence and effective symptom reporting and management to avoid impending crises.

DOI Link: doi: 10.1002/(SICI)1097-0142(19970715)80:2<250::AID-CNCR13>3.0.CO;2-T

The study was conducted to determine

• Whether patients with brain tumors could benefit from rehabilitative interventions already shown to be effective for patients with traumatic brain injury (TBI)
• Whether the resources expended on the rehabilitation of patients with brain tumors compare favorably with those expended on patients with head trauma
• Whether the benefits gained would suggest that the availability of such services on a broader scale should be encouraged.

Interventions were individualized after initial evaluation of each participant’s cognitive, behavioral, affective, and social functioning. This initial evaluation included an interview with the participant and at least one significant other. In some cases, home visits or observations of the participant in a community setting (e.g., work site) were performed.

Interventions were provided by various professionals (e.g., psychologists, speech pathologists, occupational therapists, and vocational specialists). Therapy was conducted in both individual and group settings, with a typical therapy day lasting five hours. Participants and their significant others received concurrent education and counseling services.

Measures were taken upon admission to the program, at discharge, and at follow-up (an average of eight months after discharge).

• The number of participants was 13.
• All participants had a primary malignant brain tumor. 
• All participants underwent surgical resection and radiation therapy; 12 also received chemotherapy.
• There were 8 male and 5 female participants.
• The average participant age was 34.3 ± 10 years.
• The average years of education per participant was 15.1 ± 1.7 years.
• The average time from diagnosis to admission to program was 75.4 ± 87.9 months.
• Participants were selected retrospectively based on diagnosis and availability of adequate medical records to characterize their tumors and courses of therapy.

The study took place at the Institute for Rehabilitation and Research Challenge Program in Houston, TX. 

This was a retrospective study. 

A neuropsychological test battery was conducted, with tests for the following domains: intellectual, verbal memory, visual memory, executive functions, language, visual perception, motor, and mood. The measurement instruments were unnamed.

Independence and productivity status rating scales were completed on admission, discharge, and follow-up to the program. Rating scales were shown to be sensitive to patient improvement in previous studies of patients with TBI. Specifics include:

1. An independence rating scale ranging from maximal independence, selected monitoring, and frequent monitoring to attendant care
2. A productivity status rating scale ranging from competitive employment, a modified job, educational or vocational training, homemaker role, and avocational pursuits to non-productive status.

Improved independence for six patients and improved productivity status for eight patients was demonstrated from baseline measurements. The average cost of treatment was $5,471.19 ± $3,200.73. The average number of treatment days was 20 ± 12.85.

 

 

The study provides preliminary support for the use of treatment approaches originally designed for patients with TBI.

• The study had a small sample size, with substantial variability in participants' diseases and treatment.
• The sample may not be representative of other groups of patients with brain tumors.
• The sample was based on a referral method.
• There was a short average time from treatment to follow-up.
• Participants had varied days of treatment and treatment duration.
• Ratings of independence and productivity status were potentially subject to bias.
• The study did not evaluate the means by which the rehabilitation program improved patient functioning.

DOI Link: doi: 10.1016/j.jpainsymman.2006.05.018

The intervention was cognitive behavioral therapy (CBT) offered as telepsychology. A clinical psychologist provided one-hour brief CBT to rural patients with cancer in Australia via videoconferencing. These brief CBT sessions were held weekly or biweekly for one to six sessions, depending on the patient’s Distress Thermometer rating and clinical judgment of oncology staff caring for the patient. After formal assessment, a treatment plan was individualized to include cognitive behavioral techniques, such as problem solving, activity scheduling, and controlled breathing. Each patient came to the rural clinic for the intervention. A staff member was in attendance with the patient throughout the videoconference session. Questionnaires were offered at pretreatment, post-treatment, and one month follow-up. The pretreatment questionnaire included demographic information, previous treatment by a psychologist, current use of psychotropic medications, time of initial diagnosis, and current cancer treatment prescribed.

• The sample included 25 patients with cancer living in rural Australia who scored 7+/10 on a Distress Thermometer tool or who were clinically identified by staff.
• All patients in the study received the intervention.

Rural Australia

A longitudinal pilot study design was used.

• Hospital Anxiety and Depression Scale (HADS): To assess anxiety and depression
• Functional Assessment of Cancer Therapy–General (FACT-G): To assess quality of life
• Patient satisfaction: 17 questions to assess patients’ attitudes toward their telepsychology experience postintervention

• The study needed 165 participants to make power levels: analyses of effect size was done with reported p values (p = 0.01).
• Patient anxiety levels over the intervention period decreased significantly, with large effect size sustained over one month.
• Anxiety scores (part of HADS) were F = 5.55, p = 0.01, and eta² = partial squared (magnitude of association) = 0.33.

The traditional “standard“ dose” of CBT is six to eight weeks (9–12 hrs) of therapy in a group setting. Even with this study’s “inadequate” dose of therapy, the individual, brief CBT made a significant decrease in patients’ anxiety levels.

• Lack of control group and limited sample size were significant flaws of the study.
• The study was a small pilot with numerous confounding variables (e.g., type of psychotropic medication taken, type and stage of cancer, time since diagnosis of cancer).
• Presence of a staff member during videoconference, which may have inhibited patient responses to therapy, was a minor flaw.

The intervention was CBT offered as telepsychology. A clinical psychologist provided one-hour brief CBT to rural oncology patients in Australia via videoconferencing. These brief CBT sessions were held weekly or bi-weekly for one to six sessions, depending on the patient’s ―Distress Thermometer‖ rating and clinical judgment of oncology staff caring for the patient.

After formal assessment, a treatment plan was individualized to include cognitive-behavioral techniques, such as problem solving, activity scheduling, and controlled breathing. Each patient came to the rural clinic for the intervention. A staff member was in attendance with patient throughout the videoconference session.

Longitudinal pilot study. 24 Australian rural oncology patients scoring 7+/10 on distress thermometer tool or clinical identification by staff caring for the patient received the intervention.

All patients in this study received intervention. Questionnaires offered at: pretreatment, post-treatment, and one month follow up.

Pre-treatment questionnaire included: demographic information, previous treatment by a psychologist, current use of psychotropic medications, time of initial diagnosis, and current cancer treatment prescribed.

HADS FACT-G (QOL)

Pt satisfaction asking about pt attitude toward telepsychology experience

Needed 165 participants to make power levels: analyses of effect size done with reported p values p=0.01. Patient anxiety levels over intervention period decreased significantly with large effect size sustained over 1 month. Anxiety scores (part of HADS) F=5.55, p+0.01 and n2=partial squared (magnitude of association) = 0.33.

The traditional ―standard ―dose‖ of CBT is group therapy setting of 6- 8 weeks (9-12 hrs) of therapy. Even with this study’s ―inadequate‖ dose of therapy, the individual, brief CBT made a significant decrease in anxiety levels.

A significant flaw of this study is lack of control group and limited sample size. This is a small pilot study with numerous confounding variables (type of psychotropic medication taken, type and stage of cancer, time since diagnosis of cancer).

A minor flaw was the presence of staff member during videoconference as this may have inhibited patient responses to therapy.