PHASE OF CARE: Active antitumor treatment

The authors provide tables summarizing the emetogenic potential of common chemotherapy agents, the National Cancer Institute's classification of emesis by intensity and severity, and an algorithm of chemotherapy-induced nausea and vomiting (CINV) prophylaxis. Recommended schedules for the administration of palonosetron and dexamethasone are also provided.

No succinct list of recommendations was provided by the authors. The definition of nausea is also inconsistent with the National Comprehensive Cancer Network's definition. The article describes the different types of CINV, describes the emetogenic potential of agents, and supports an algorithm to select appropriate interventions. The authors do not state their intention outright; however, this document appears to present treatment guidelines for the Spanish Society of Medical Oncology. This guide is written in a clear style and offers straightforward recommendations for the prevention and treatment of CINV. The recommendations are grounded in the evidence, although no explanation of how the evidence was retrieved is provided. It is not possible to tell if research is drawn from a suitable representation of sources to be deemed comprehensive. Forty-three references were cited ranging from 1993 to 2013. It is assumed that the recommendations are applicable towards adults and not pediatrics but this was not stated. Recommendations for refractory and salvage antiemetic therapy are provided, but it is unclear how consensus was reached for these recommendations.

• Limitations were not explicated by the authors.
• Explanation of article retrieval is not provided.
• Procedure for reaching recommendation is not provided.
• To what degree was a consensus reached and how members resolved issues when consensus could not be reached are examples of this report’s limitations.

CINV continues to be a serious and debilitating side effect of chemotherapy for patients with cancer. Nurses should be well informed of current recommendations and guidelines for the use of 5HT3s in the prevention and treatment of CINV.

To evaluate the use of colchicine solution in the treatment of mucositis in patients with hematologic malignancies undergoing chemotherapy

Group A (control) used a 9% sodium chloride (NaCl) and water solution. Group B used a colchicine solution of 2 mg dissolved in 500 cc of sterile water starting the first day of symptoms of oral mucositis until the fifth day of the disease (inflammatory phase). Following the fifth day, patients in group B received same as group A. The solution for both groups was prepared fresh every morning. Both groups gargled for two minutes, four times a day while being supervised by a researcher. Twice a day, patients brushed with a soft toothbrush, if possible. During the study, patients were allowed concomitant interventions for oral mucositis (OM), such as systemic antibiotics, antimycotics, antivirials, antiemetics, analgesics, and granulocyte colony-stimulating factor (G-CSF) support. Cryotherapy and other oral mouthwashes were not permitted.

• The study reported on 82 patients, with a median age of 42 years in group A and 50 years in group B.
• The sample had 37 females and 45 males.
• Patients had OM and had been diagnosed with lymphoma or acute leukemia treated with high-risk chemotherapy.

The study was conducted in an inpatient cancer center in Bogota, Columbia.

This study used a single arm, nonrandomized, sequentially enrolled, historical control group.

• Oral assessments were done once a day until resolution using the World Health Organization (WHO) Oral Toxicity Scale.
• Oral pain was evaluated twice a day using a visual analog scale (VAS).
• Tolerability of mouthwash was evaluated by the patient once daily using a VAS.
• Maximum daily body temperature was recorded until OM was resolved.
• The characteristics, severity, and duration of OM, length of inpatient hospitalization, severity of OM-related pain, days of opioid consumption, tolerability of mouthwashes, change in oral pH (using pH meter), and occurrence of infection were evaluated using the Mann-Whitney test and Fisher’s exact test.
• Statistical analyses were performed using the SPSS 12.0 Statistical package.

• Patients in the treatment group experienced significantly lower median duration of OM (6 days versus 9 days) (p = 0.028).
• Patients in the treatment group experienced significantly fewer median days to healing of mucosal lesions (4 days versus 7 days) (p = 0.047).
• No differences were found in the number of days of hospitalizations, variations in weight, voice characteristics, salivation production, mucosal pH, and frequency and volume of oral mucosal bleeding.
• Oral pain assessment was similar, and no significant differences were found in opioid consumption.
• No differences were found in tolerability of mouthwashes.
• No serious side effects were reported with colchicine mouthwash.
• No differences were found in incidence of febrile neutropenia.

Colchicine mouthwash may be helpful in reducing the severity and duration of chemotherapy-induced OM.

• The sample size was small.
• The study was not randomized or blinded.
• Patients were able to use multiple other interventions for mucositis. Use of these interventions was not reported or discussed, so one cannot tell which interventions actually had an effect.

Further studies are needed to confirm results. This was done in an inpatient setting under direct supervision; these findings may not be applicable in other situations.

To evaluate two different dose escalation approaches for the combination of oxycodone and pregabalin

Patients were randomized to receive either 20 mg per day sustained-release oxycodone and escalating doses of pregabalin starting at 50 mg per day, or to pregabalin at 50 mg per day and escalating doses of oxycodone. Patients were observed for 14 days. The primary endpoint of the study was overall analgesia, defined as pain intensity reduction by at least one-third on a numeric rating scale.

• N = 67
• MEAN AGE = 67.5 years
• AGE RANGE = 39–85 years
• MALES: 56.7%, FEMALES: 43.3%
• KEY DISEASE CHARACTERISTICS: Lung, breast, and colon cancer were most prevalent.
• OTHER KEY SAMPLE CHARACTERISTICS: 72% had baseline pain scores of 6 or lower.

• SITE: Multi-site 
• SETTING TYPE: Outpatient 
• LOCATION: Italy

• APPLICATIONS: Palliative care

• Randomized, parallel group

• Pain numeric rating scale
• Allodynia recorded as present or absent by physical exam
• Patient diary for daily recording of pain severity, use of other medications, and episodes of breakthrough pain

Analgesia as defined was achieved in the pregabalin escalation group with a mean dose of 100 mg and in the other group with a mean dose of 60 mg oxycodone. No differences were seen between groups in use of rescue medication, other analgesics, or side effects.

Strategies for managing neuropathic pain with either dose escalation of pregabalin or escalation of sustained-release oxycodone when given in combination produced similar results.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Other limitations/explanation: Short duration of the study

Findings suggest that similar pain management effects can be achieved with either escalation of pregabalin or escalation of oxycodone when given in combination for neuropathic pain. These findings suggest that either approach may provide similar effects and that the approach used can be determined according to relevant patient characteristics and preferences.

To evaluate the efficacy and safety of aprepitant in combination with palonsetron and dexamethasone in patients receiving three-day cisplatin-based chemotherapy

• Patients received three-day cisplatin-based chemotherapy and had never been treated with aprepitant. 
• All patients received the same antiemetic regimen of aprepitant 125 mg orally before chemotherapy on day 1 and 80 mg orally once daily on the following two days. 
• Palonosetron was given on days 1 and 3, and dexamethasone was given on days 1, 2, and 3. 
• The study physician evaluated efficacy and safety daily for seven days.  
• Patients were evaluated over multiple cycles of chemotherapy if applicable.

• The study consisted of 41 patients receiving a total of 89 cycles of chemotherapy.
• The median age of participants was 52.8 years (range = 21-74 years).
• Twenty-four patients (59%) were male, and 17 (41%) were female.
• Diagnoses were lung (32), nasopharyngeal (3), testicular (2), esophagus (2), stomach (1), and oropharyngeal (1).
• Eight of the patients were chemotherapy-naïve; 27 patients had a history of smoking, 16 had a history of drinking, 11 had a history of motion sickness, and 12 had a history of morning sickness.

This was a single-site study conducted in Guangzhou, China.

All patients were in active treatment.

This was a prospective, nonrandomized study.

Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute, version 3.0, was used to assess nausea and safety.

• Findings indicated that 17% of patients had no nausea, 54% had grade 1 nausea, and 29% had grade 2 nausea. 
• With regard to vomiting, 63% had no vomiting in the acute phase, 78% had no vomiting in the delayed phase, and 58.5% had no vomiting overall. The number of patients reporting no vomiting decreased from 85% on day 1 of chemotherapy to 65% on day 3. 
• The most common side effects were hiccups (37%), fatigue (17%), headache (15%), and constipation (12%).  No adverse events were grade 2 or more. No cumulative toxicities from multiple chemotherapy cycles were reported.

Triple antiemetic medications of aprepitant, palonosetron, and dexamethasone are safe and effective for multiple-day chemotherapy to prevent vomiting.  The antiemetic efficacy is maintained during multiple chemotherapy cycles. The regimen was not as effective in preventing nausea.

• This study had a small sample of fewer than 100 participants.
• No control group was included. 
• The study was conducted at a single institution. 
• This was a nonrandomized study. 
• Descriptions of how the variables were measured were poor. For example, no information was provided on how vomiting was monitored and recorded.

Using the combination of aprepitant, palonosetron, and dexamethasone is effective in decreasing the incidence of chemotherapy-induced nausea and vomiting (CINV) in multiple-day chemotherapy regimens with low incidence of toxicity. Control of the symptom of nausea remains problematic.

To determine the effectiveness of nerve blocks to control pain in patients with end-stage pancreatic cancer pain

Patients were randomized to two groups, the sham and nerve block groups. Visual Analog Scale (VAS) pain scores, pain duration, reduction of other analgesics, and quality of life scores (measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30]) were obtained before and three months after intervention.

• N = 100  
• MEAN AGE = 65.5 years
• MALES: Unknown, FEMALES: Unknown 
• KEY DISEASE CHARACTERISTICS: Unresectable or inoperable carcinoma of the pancreas by CT or EUS; stage determined by the 2010 American Joint Committee on Cancer (AJCC) manual; presence of midabdominal pain at a minimum of two days per week for at least one hour per day; INR 1.5; platelets greater than 50,000; life expectancy greater than three months
• OTHER KEY SAMPLE CHARACTERISTICS: Age had to be greater than 18; excluded if unable to sign consent; excluded if patient had previous blocks; excluded if patient had chronic pancreatitis

• SITE: Not stated/unknown    
• SETTING TYPE: Not specified    
• LOCATION: Not specified; approved by Soochow University Ethical Committee in China

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Elder care, palliative care 

Sham-controlled, randomized, controlled trial

• Visual Analog Scale (VAS)
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

This study presents a potential additional intervention in combination with pain medication in patients with end-stage pancreatic cancer-associated pain. Additional potential benefits could be the improvement of physical and emotional function, fatigue, insomnia, and loss of appetite. This study would have to be replicated with a larger sample size to prove efficacy.

• Findings not generalizable
• Other limitations/explanation: Follow-up period was limited to three months; location of tumor was not identified; prior therapies not identified; less generalizable sample size 100

This type of therapy presents a potential intervention in combination with pain medication for pain control in end-stage pancreatic cancer based on this randomized, controlled trial. After-care of a patient with a nerve block would require training. An assessment of the adjustment of other medicinal treatments would be required at baseline in this intervention.

This study intended to test the effectiveness of a comprehensive menopausal assessment (CMA) on symptom relief, quality of life, and sexual functioning.

Participants were randomized by age (≤55 and >55) and tamoxifen use (current vs. not used). The CMA was delivered by a trained nurse practitioner with a specialty in family and women’s health over a 4-month period and focused on structured symptom assessment of hot flashes, vaginal dryness, and stress urinary incontinence. After assessment, patients were provided with individualized education and counseling, psychosocial support, referrals, and individualized follow-up. Specific pharmacologic and behavioral interventions for the target symptoms were implemented to control symptoms based on treatment protocols developed by the NP and the study physician. The intervention group returned for a 2-month follow-up visit. The usual care group received a telephone call 2 months after baseline to ask about therapies used to manage their symptoms. Data was collected at baseline and 4 months. The usual care group was then able to take part in the CMA but no further data was collected.

• The study enrolled 42 women with breast cancer.

• SITE:  Single site    
• SETTING TYPE : Outpatient    
• LOCATION: California/community recruitment

PHASE OF CARE: Late effects and survivorship

This was a randomized, controlled trial.

• Menopausal Symptom Scale Score (adapted from the Breast Cancer Prevention Trial Symptom Checklist)
• Vitality Scale from the RAND 36-item Health Survey (aka Medical Outcomes Study SF-36)
• Sexual Summary Scale from the Cancer Rehabilitation Evaluation (CARES)

97% of women in the study reported hot flashes at baseline, with no difference between groups. There was a significant difference in the menopause symptom scale (p=.0004), with women in the intervention group showing the most improvement in symptoms. There was no difference between groups in QOL (p=.77). The CMA group had significantly better sexual functioning at follow-up compared to the usual care group (p=.02). No specific data on improvement in hot flashes was provided. Only the overall symptom scale was reported.

CMA is an effective intervention to improve/reduce the number of menopausal symptoms in breast cancer survivors and to improve sexual function for these women.

Limitations of the study included:

• Small sample (< 100)
• Risk of bias (no blinding)
• Intervention expensive, impractical, or training needs
• Requires a specially trained nurse practitioner for the intervention

A nurse-led intervention to target menopausal symptoms is an effective way to reduce these symptoms in women who are survivors of breast cancer. However, the intervention may be too expensive or impractical given the training requirements of the intervention nurse and institutional guidelines on billable appointments.

To evaluate the effects of prophylaxis with levofloxacin in relapsed/refractory acute myeloid leukemia (AML)

Data were obtained from medical records of patients with relapsed or refractory AML admitted from 2006–2015. Standard levofloxacin prophylaxis was begun in 2013 with 500 mg once daily on day 1 of chemotherapy and continued until neutrophil recovery. Cohorts who received levofloxacin were compared to a cohort that did not receive prophylaxis.

• N = 145   
• MEDIAN AGE = 58–59 years
• AGE RANGE = 18–84 years
• MALES: 67%, FEMALES: 33%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had relapsed AML and were undergoing re-induction chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients on broad spectrum antibiotics or who were receiving other prophylaxis were excluded. Eighteen percent had previously undergone hematopoietic cell transplantation.

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

PHASE OF CARE: Active antitumor treatment

Retrospective cohort comparison

Febrile neutropenia (FN) was defined as an oral temperature of 38.3 C or greater with and absolute neutrophil count less than 500 cells/mm³

A lower rate of bacteremia existed in the prophylaxis group, but the difference was not significant. The time to onset of bacteremia from onset of neutropenia was delayed in the prophylaxis group compared to others (p = 0.012). No differences in drug-resistant organisms existed between cohorts, or in the incidence of FN. In the prophylaxis group, the frequency of gram-negative organism–related infections was lower.

Levofloxacin prophylaxis reduced the number of overall infections and the prevalence of gram-negative infections in patients being treated for relapsed or refractory AML.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)

The findings suggest that antibiotic prophylaxis is beneficial for patients undergoing re-induction chemotherapy for relapsed or refractory AML.

Patients chewed five to six pieces of fluoride-containing, sugar-free gum, sweetened with xylitol per day for 20 minutes per piece from the first day of chemotherapy to three days after course of treatment. Both groups practiced standard oral care, consisting of brushing teeth with a soft toothbrush and rinsing with sodium bicarbonate rinse.

• The study reported on 145 children ages 5–18 years. The gum group had 73 patients, and the control group had 72 patients.
• All patients were scheduled to receive chemotherapy associated with at least a 30% rate of grade 3–4 oral mucositis according to the World Health Organization (WHO) oral mucositis grading scale.

The study was conducted between March 1999 and December 2002.

This was a randomized, controlled trial.

Researchers recorded the WHO grade of mucositis within first 21 days, time to development of grade 3–4 mucositis, incidence of any grade of mucositis, incidence of pain using a 70-point visual analogue scale, number of days of total parenteral nutrition, incidence of abdominal symptoms, and incidence of septicemia.

No significant differences were found between arms for severe mucositis endpoints.

Patients receiving less toxic regimens had a decrease in WHO grade 1–4 oral mucositis of 49% in the gum group and 72% in the control group (p = 0.03).
 

• This study did not achieve adequate sample size according to power analysis.
• Eight children discontinued using the gum because of nausea.
• Chlorhexidine and fungizone were widely used in both arms.

Participants in the treatment group received infusions of calcium gluconate and magnesium sulfate (1 g) before and after oxaliplatin. The chemotherapy protocol consisted of combination oxaliplatin, 5-fluourouracil (5-FU), and leucovorin. Three regimens of oxaliplatin were used: 85 mg/m² every two weeks, 100 mg/m² every two weeks, or 130 mg/m² every three weeks.

A total of 161 patients were enrolled in the study, with 96 placed in the treatment group and 65 in the control group.

The study had a retrospective design.

Toxicity was graded every one to two weeks by staff according to the National Cancer Institute's Common Terminology Criteria for Adverse Events and an oxaliplatin-specific neurotoxicity scale that assessed paresthesias.

Paresthesias, trismus, cramps, limb pain, and diarrhea were significantly less frequent in the treatment group. Pharyngolaryngeal dysesthesia were never reported in the treatment group versus 9% in the control group. In addition, less grade 3 toxicity was reported in the treatment group compared to the control group. At the end of oxaliplatin therapy, 65% of participants in the treatment group had no evidence of chemotherapy-induced peripheral neuropathy (CIPN) compared to 37% in the control group. By the end of treatment, 20% of patients in the treatment group showed evidence of CIPN versus 45% in the control group. Patients with grade 2 or 3 neurotoxicity at the end of treatment with oxaliplatin (85 mg/m²) recovered more rapidly from CIPN than those in the control group.

• The study was retrospective and not randomized or blinded.
• Staff who performed the assessments may have been biased in reporting.
• More patients who received either FOLFOX 4 or FOLFOX 6 regimens were included in the treatment group, making results more open to bias and placebo effect.

To compare the effectiveness of orally administered red morphine drops (RMD) and subcutaneous morphine (SCM) in patients with advanced lung cancer

Patients were randomized to two groups. Group 1 received oral RMD and a subcutaneous injection of isotonic saline. Group 2 received a placebo oral RMD and a subcutaneous injection of morphine. All injections were given in the leg in a location without edema. Patients were instructed to hold the RMD or placebo RMD solution in their mouths as long as possible before swallowing. The study preparations included a) morphine hydrochloride at 2 g, ethanol 96% at 5 g, cochenille tincture PhD.48 10 g, purified water up to 100 g (one drop corresponded to 0.6 mg morphine), b) ethanol 96% at 5 g, cochenille tincture PhD.48 10 g and purified water up to 100 g, c) injectable morphine 20 mg/ml, and d) isotonic saline. Measurements were taken at baseline and five, 10, 15, 20, 30, and 60 minutes after medication administration. Patients were not allowed to take any opioid within four hours prior to the experiment.

• N = 20  
• MEAN AGE = 69 years (range = 42–84 years)
• MALES: 10%, FEMALES: 90%
• KEY DISEASE CHARACTERISTICS: Lung cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Terminally ill patients receiving opioids for pain; resting dyspnea of at least 3 on 0–10 Visual Analog Scale at rest

• SITE: Single site    
• SETTING TYPE: Not specified  
• LOCATION: Denmark

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

Double-dummy randomized, controlled trial

• Visual Analog Scale (VAS) 0–10 to assess the severity of dyspnea
• Respiratory rate
• Oxygen saturation
• Pulse rate

There was no significant difference in dyspnea between the two groups. Both RMD and SCM showed a significant decrease in dyspnea (time p = 0.0451, and treatment p < 0.0001). In addition, RMD and SCM were associated with significant decreases in pulse rate (p = 0.0410). Although it was not statistically significant, patients receiving SCM showed a more rapid decline in dyspnea. Patients in the RMD group received 3.3%–8.6% of their total 24-hour opioid dose. Patients in the SCM group received 1.5%–5.5% of their total 24-hour opioid dose.

Both RMD and SCM improved dyspnea in terminally ill patients.

• Small sample (< 30)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Other limitations/explanation: Primarily women in the sample; baseline dyspnea was 1 higher in the RMD group

RMD is a reasonable alternative to SCM and should be considered as part of patient preference at the end of life. Subcutaneous administration may provide more rapid relief. It is noteworthy that opioid use relieves dyspnea for patients receiving regular opioids for pain management. The most effective dosage of RMD is not yet known. Additional research to understand the pharmacokinetics of RMD is needed.