STUDY PURPOSE: To evaluate the effects of nonpharmacologic interventions on patient-reported sleep, pain, and well-being in people with cancer and other conditions

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 11
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,066
• SAMPLE RANGE ACROSS STUDIES: 28–276
• KEY SAMPLE CHARACTERISTICS: Included cancer, arthritis, fibromyalgia, musculoskeletal pain, and headache as painful conditions; six studies were of patients with cancer

PHASE OF CARE: Not specified or not applicable

All treatments had at least one component of cognitive behavioral therapy for insomnia. Subgroup analysis showed that the interventions tested were significant for both cancer and noncancer cases. Another subgroup analysis showed that effectiveness was significant for face-to-face interventions but not for those conducted via the phone or Internet. Analysis showed effects for sleep (standard mean difference [SMD] = 0.78, p < 0.0001 with high heterogeneity), pain (SMD = 0.18, p = 0.05), and fatigue (SMD = 0.38, p = 0.01).

Nonpharmacologic interventions involving components of cognitive behavioral therapy for insomnia were shown to be effective in improving sleep, pain, and fatigue among patients with and without cancer.

High heterogeneity

Interventions like cognitive behavioral for insomnia are beneficial to improve sleep, reduce fatigue, and positively affect pain.

To test the theory that the local benefit of opioids is related to opioid binding sites in peripheral bronchus.

Patients were given 20 mg of morphine dissolved in 5 mL of normal saline administered through an ultranebulizer. If no subjective relief resulted, the dose was increased to 40 mg and was tried again after four hours.

• The sample was comprised of 15 patients with thoracic cancer without cognitive changes who had dyspnea that was difficult to control with standard treatment (e.g., pleural drainage, antibiotics, and diuretics). 
• Median age was 61 years. 
• Seven patients were on continuous oxygen by cannula.
• Ten patients were already on systemic opioids.

Inpatient hospital in Japan

This was a pilot, open-label, nonrandomized, uncontrolled study.

• Dyspnea visual analog scale (VAS) was measured at baseline and at 60 minutes after inhalation.
• Outcome criteria was an improvement greater than 10% decrease in VAS.
• Respiratory rate (RR), hemoglobin, and oxygen saturation were also measured.
• A questionnaire about adverse effects and preferences was administered.

Significant decrease occurred in VAS after nebulization (p = 0.005). Eight of 15 patients evaluated treatment effective and requested continuation. No significant change occurred in RR or oxygenation. A not statistically significance tendency was found for patients on systemic opioids to benefit more compared to nonopioid patients.

• The study had a small sample size and was uncontrolled.
• The intervention placebo effect cannot be ruled out.
• The dose increase without a washout period possibly contaminated the findings.

To compile evidence from randomized controlled trials, case series, and case reports to identify the effectiveness of various therapeutic agents for prevention and treatment of skin toxicities associated with epidermal growth factor receptor (EGFR) inhibitor therapy

DATABASES: PubMed (January 2002–May 2009) and SCOPUS (January 2002–March 2009), manual searching for retrieval of additional references from articles reviewed

KEYWORDS: EGFR inhibitor, cetuximab, erlotinib, gefitinib, panitumumab, management, skin toxicity, and cutaneous effects

INCLUSION CRITERIA: Clinical trial, case series, case report, or clinical management guideline that studied treatment options of EGFR inhibitor-induced skin toxicities; EGFR inhibitor dosing regimen and treatment outcomes included in the publication

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Authors do not state the total volume of literature reviewed or decision-making regarding article exclusion processes. Authors report that randomized controlled trials, case series, and case reports were retrieved.

• FINAL NUMBER STUDIES INCLUDED = Final reports included in the analysis were two randomized controlled trials, three case series, and 10 case reports.
• TOTAL PATIENTS INCLUDED IN REVIEW = 156

Interventions were categorized as preventive intent or treatment intent. Interventions included in the review were topical antibiotics, systemic antibiotics, antiseptics, topical corticosteroids, retinoids, and other products. The majority of interventions were reported regarding effectiveness with EGFR inhibitor rash. Pruritus associated with the EGFR inhibitor-induced rash was documented in 47 patients in seven case reports; however, only three reports addressed pruritus treatment. Management of xerosis was mentioned in three case reports and one case series, for a total of 20 patients.

Preventive intent findings:

• Interventions found included topical erythromycin solution, systemic tetracyclines, and topical retinoid (tazarotene cream in combination with systemic antibiotics).
• Erythromycin solution was provided to two patients. These patients experienced only slight erythema without pustules, suggesting a protective effect.
• Two randomized controlled trials investigated the use of systemic tetracyclines to prevent EGFR inhibitor rash. In the total 51 patients across these trials, systemic antibiotic treatment did not prevent rash. Findings did suggest that the use of systemic antibiotic treatment along with EGFR inhibitor can decrease the severity of the rash during the first month of EGFR inhibitor treatment.
• Tazarotene cream, in combination with minocycline, demonstrated no effect on rash severity in 39 patients. The retinoid also was associated with significant skin irritation, causing one-third of the patients to discontinue its use.

Treatment intent findings:

• Interventions found for treatment of EGFR inhibitor skin toxicity included topical antibiotics, systemic antibiotics, antiseptics, topical corticosteroids, retinoids, colloidal sulfur galenic cream, and cream containing urea and vitamin K.
• Topical antibiotics were the most common treatments and were most often used in combination with other topical agents or systemic antibiotics. This intervention was reported in 49 patients.
  • Topical antibiotics used included clindamycin, erythromycin, fusidic acid, and metronidazole.
  • The majority of cases had either partial or complete responses with treatment.
• Systemic antibiotics were used to treat more severe EGFR inhibitor-induced rash in a total of 16 patients in several case reports and case series. Systemic tetracyclines were used in 12 patients in combination with topical medications for treatment of rash. In seven patients, non-tetracycline compounds (e.g., penicillin, clindamycin, fusidic acid) were used in combination with various topical agents.
  • Mixed results were seen. Some patients had complete or partial response, but in 58% of cases, results were confounded by concomitant delay or dose reduction in EGFR inhibitor treatment.
  • Results with non-tetracycline compounds also were confounded by withdrawal of EGFR inhibitor treatment.
• Antiseptics, including povidone iodine, hexamidine, benzoyl peroxide, and boric acid were reported in seven cases. In all cases, these were used in combination with other topical or systemic drugs. Response to these interventions was confounded by concomitant EGFR inhibitor dosage reduction in two patients who had a “complete response” to intervention with antiseptics.
• Retinoid interventions for rash treatment included oral isotretinoin in four patients and topical adapalene in three patients.
• Other intervention reports were retrieved that involved use of topical sulfur galenic cream and a cream containing urea and vitamin K. Improvement in these three patients was reported.

Strong evidence supports the use of topical antibiotics to manage EGFR inhibitor skin toxicities. Antibiotics are the most common treatment option. Use of anti-acne medications such as benzoyl peroxide and retinoids is controversial. Steroids are not recommended until well-designed clinical trials can demonstrate efficacy because steroid use can aggravate and induce acne.

This review did not identify strong evidence for any of the interventions reported for the management of skin toxicities associated with EGFR inhibitors. Antibiotics are most frequently used to manage EGFR inhibitor-induced skin toxicities, and more reports are available on the use of antibiotics than on the use of other approaches. The authors concluded that the evidence in support of the use of antibiotics is questionable. In this review, the total number of cases involved in the use of topical antibiotics was 49, and the total number of cases involved in the use of systemic antibiotics was 68. In many of the cases for systemic antibiotic use, reported findings were confounded by the additional intervention of dose modification (i.e., EGFR inhibitor dosages were reduced, delayed, or stopped).

• Reports reviewed involved a variety of mixed interventions, so identifying the combinations of interventions that appear to have the greatest promise for successful management of EGFR inhibitor-induced skin toxicities is difficult.
• This review only focused on skin toxicities associated with EGFR inhibitors. Little information on toxicities other than skin rash was found.
• This review, as well as the current literature evaluating the interventions, had a number of limitations. The review was limited by a lack of information found on pruritus and xerosis, as well as a lack of substantive, well-controlled research in this area. Most reports gave information about the resolution of rash in terms of lesion count but did not evaluate patient symptoms or specific patient-centered outcomes.
• Most reports did not provide a determination or measurement of the severity of skin problems. Most studies did not conduct a follow-up to determine long-term resolution. Reports of complete resolution of skin rash often involved discontinuation or dose reduction of the EGFR inhibitor, so efficacy of the intervention is likely to have been overestimated.

This review emphasized the need for well-designed research in this area that includes appropriate follow-up strategies. This review also discusses the widespread use of antibiotics to treat EGFR-induced skin toxicities. It notes that topical antibiotics are recommended for treatment of milder skin reactions, and systemic antibiotics (e.g., minocycline or doxycycline) are recommended for treatment of more severe rash. The authors state that their recommendations are aligned with several proposed treatment algorithms that have been obtained from international and interdisciplinary EGFR inhibitor dermatologic toxicity forums. As evident in this review, these recommendations are not based on strong evidence.

• FINAL NUMBER STUDIES INCLUDED = 21
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,713
• KEY SAMPLE CHARACTERISTICS: Patients were aged 6–80 years and were recruited from inpatient settings and outpatient clinics. The average sample size was 81 patients. The studies focused on a variety of malignancies including breast cancer, lung cancer, leukemia, gastrointestinal cancer, and (in one study) pediatric cancer.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Pediatrics and elder care

• Effective rate of AT with acute CINV: 44.44%–93.33% intervention group; 15%–91.67% control group
• Effective rate of AT with delayed CINV: 62.96%–100% intervention group; 25%–100% control group
• Studies comparing antiemetics versus antiemetics plus AT found the intervention group more effective. Intervention group: 54.62%–100%; control group 34.38%–100%
• Four studies investigated the effect of auricular acupressure on either acute or delayed CINV. There was no concordance of results. Some studies showed more improvement in acute, some in delayed, and some showed no difference.
• Three studies that included information about the performance statuses of patients using the Karnofsky Performance Status (KPS) index demonstrated a favorable effect on KPS scores in the intervention group compared to the control group.
• Twenty studies did not monitor patient compliance with the intervention, and the length of pressing acupuncture points varied from 30 seconds to 5 minutes.

This review was a helpful starting point to spur more research on the use of AT for the management of CINV. There was significant heterogeneity among the trials, but there appeared to be encouraging results for the use of AT to justify additional research. To better answer the question about AT's benefit, well-designed, randomized, controlled trials will be needed. From the information presented, it appears that AT may have a role in the management of delayed CINV, which can be challenging to manage and very troublesome for patients.

The investigators were only able to evaluate English and Chinese studies, which may have prevented the review of other studies such as Korean trials.

Encouraging results were identified about the adjunct use of AT for CINV, but this review demonstrated the need for well-designed trials incorporating AT with antiemetic regimens for acute and delayed CINV. The trials need to incorporate standard AT points, standard pressing length at each point, and a standard CINV assessment scale. Patient compliance also should be assessed and documented.

STUDY PURPOSE: To evaluate the efficacy of anesthetic wound infusion for analgesia in women undergoing breast cancer surgery

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 13
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,150
• SAMPLE RANGE ACROSS STUDIES: 30–238 patients
• KEY SAMPLE CHARACTERISTICS: All had undergone breast cancer surgery

PHASE OF CARE: Active antitumor treatment

Meta-analysis was done to compare groups for pain severity at 1, 2, 12, and 24 hours. Meta-analysis showed no difference between groups. Analysis did not show any statistically significant difference in analgesic consumption. No adverse events were identified.

Findings did not show significant differences in pain outcomes between those given local anesthetic wound infiltration and those given standard care.

• High heterogeneity
• Low sample sizes

Findings suggest that infusion of ropivacaine or bupivacaine following breast cancer surgery did not provide significant clinical benefit in terms of pain severity or postoperative analgesic needs. Individual studies showed mixed results, and high heterogeneity existed across studies, a limitation of this analysis.

To assess the safety and efficacy of fentanyl buccal tablets (FBT) in breakthrough pain (BTP) management when given in combination with around-the-clock (ATC) opioids and to explore the influence of dose adjustments on breakthrough pain management

Before the maintenance phase, the FBT dose that was successful in providing sufficient pain relief without producing unacceptable adverse events was identified by titration. During the 12-week maintenance phase, the FBT dose was administered for BTP episodes. The successful dose ranged from 100–800 ug for patients who received an ATC opioid dose of 60–1,000 mg per day of oral morphine and from 50–800 ug for those who received from 30– < 60 mg per day of oral morphine equivalents. Patients were allowed to take additional supplemental medications including FBT when no pain relief was perceived by 30 minutes after FBT administration. FBT or ATC opioid doses could be changed if additional supplemental medications (including FBT) were frequently administered for BTP episodes or if there were five or more BTP episodes per day. FBT could be administered eight times per day for a maximum of six BTP episodes per day. Prestudy medications were given for the seventh or more BTP episode in a day of if the BTP episode occurred within four hours after a FBT administration.

• N = 82  
• AGE = 20 years and older
• MALES: 60%, FEMALES: 40%
• KEY DISEASE CHARACTERISTICS: Patients with cancer-related pain caused by solid or hematologic tumors and a life expectancy of three months or longer. Participants had to receive ATC opioid regiments to control their pain for at least one week prior to enrollment and had to experience one to four BTP episodes per day that had been controlled with supplemental medications.  
• OTHER KEY SAMPLE CHARACTERISTICS: Ability to evaluate pain in a self-recording diary; performance status grades 0–2 based on the Eastern Cooperative Oncology Group (ECOG) guidelines; exclusion included diseases or symptoms that could affect safety, oral conditions that could interfere with FBT application, clinical disorders that could compromise data collections (e.g., psychological), or concomitant medications including monoamine oxidase inhibitors, narcotic antagonist analgesics, narcotic antagonists and drugs administered for other clinical trials

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: 34 sites in Japan

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Open-label study

• Pain intensity, pain relief, a global medication performance assessment, and an overall impression of FBT treatment were evaluated with each FBT administration.
• Safety included vital signs, arterial oxygen saturation, and the frequency and severity of each adverse event.

Forty-one patients completed the 12-week maintenance phase. A major reason for discontinuation was adverse events. No patients discontinued because of a lack of treatment efficacy. Treatment-related adverse events were reported by 37% of patients during the maintenance phase. The most common adverse events were somnolence (16%) and nausea (10.7%). Five deaths occurred during the study, none of which were related to FBT. Both the FBT and ATC opioid doses gradually increased over time from the beginning of the maintenance phase. The breakthrough FBT dose was changed in 42 patients (56.8%). The ATC opioid dose was changed in 50 patients (67.5%).

FBT has sustained analgesic effect and was well tolerated. Quality of life was reported to improve with stable or improved pain intensity, which was not clearly measured in this study. FBT was noted to be safe for long periods of time even with needed increase in its dose.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Single-arm trial; quality of life not measured; limited duration of study

Pain management is an important aspect of improving a patient's quality of life. Nurses play a key role in assisting patients and providing pain management medications and in teaching patients how to manage their pain when they are outside an inpatient facility. Additional agents need to be available to assist in optimal pain control.

To evaluate the efficacy of the triple therapy of aprepitant, palonosetron, and dexamethasone in patients with gynecological cancer receiving highly emetogenic chemotherapy

Women with gynecological cancer who were receiving highly emetogenic chemotherapy received 125 mg PO aprepitant before chemotherapy on day 1 and 80 mg on days 2 and 3, 0.75 mg of IV palonosetron before chemotherapy on day 1, and 9.9 mg of PO/IV dexamethasone before chemotherapy on day 1 and at 6.6 mg on days 2–4. The primary aim was to evaluate the number of patients with a complete response (CR) overall, which was defined as no vomiting and no use of rescue medication during the entire study period (0–120 hours postchemotherapy). The secondary aims were (1) to evaluate CR in the acute (0–24 hours postchemotherapy) and delayed (24–120 hours postchemotherapy) phases of treatment and (2) to evaluate complete protection (CP) defined as no vomiting, no rescue therapy, and no significant nausea overall and during the acute and delayed phases of treatment.

• N = 96  
• MEDIAN AGE = 55 years (range = 32–75 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Gynecologic cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Patients receiving highly emetogenic chemotherapy that included cisplatin ≥ 50 mg/m².

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

• PHASE OF CARE: Active antitumor treatment

Prospective, multi-center study

No information was provided on the measurement of nausea and vomiting. A Visual Analog Scale (VAS) may have been used, although this was not expressly stated and the range and timing of administration of the VAS was undefined.

For the primary aim, overall CR rate was 54.2 %. For the secondary aim, evaluating the number of patients with CR in the acute and delayed phases of treatment, CR was 87.5% in the acute phase of treatment and 56.3% in the delayed phase of treatment. For the secondary aim evaluating CP overall and during the acute and delayed phases of treatment, CP overall was 44.8%, CP during the acute phase of treatment was 82.3%, and CP during the delayed phase of treatment was 45.8%.

• Small sample (< 100)
• Risk of bias (no control group)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Findings not generalizable
• Other limitations/explanation: No information was provided as to how the authors assessed nausea and vomiting, and as such we cannot know how valid or reliable the method of assessment was. The findings are only applicable to Japanese gynecological patients at this stage until further testing can take place in a more diverse sample.

CINV is often difficult to control and is especially prevalent in female patients. The combination of aprepitant, palonosetron, and dexamethasone has comparable rates of CR and CP when compared to other antiemetic regimens; however, the population used in this study has been shown to be at greater risk for severe CINV. This should be a recommended antiemetic regimen for gynecological patients receiving highly emetogenic chemotherapy.

To evaluate the use of oral alkalization (OA) with control of defecation (CD)

• Patients were given OA, consisting of 0.5 g NaHCO₃ (sodium bicarbonate) and 0.5 g magnesium oxide, after meals and at bedtime with basic water (pH > 7.2) continuously for a total of 1,500-2,000 mL/d and 100 mg oral ursodeoxycholic acid 100 mg po 1–4 times daily after meals.
• For CD (administering laxative treatment to avoid long contact time of irinotecan metabolite with bowel mucosa), patients were given up to 4 g per day of magnesium oxide and 2 L per day of excess basic water.
• If patients experienced watery diarrhea with OA and CD, magnesium oxide was discontinued until symptom resolution.

• The study evaluated Japanese patients with small cell lung cancer or nonsmall cell lung cancer.
• Group B consisted of 37 consecutive patients from three ongoing, prospective, phase I/II studies receiving irinotecan in combination with cisplatin in the presence of OA and CD.
• Group A consisted of 32 control subjects without OA and CD who were matched to the background characteristics of the case patients treated with irinotecan and cisplatin.

The study was conducted at a single institution.

This was a case-control study.

• Intraluminal pH, hematologic toxicity, and nonhemotologic toxicity were evaluated.
• Gastrointestinal (GI) evaluation included recording appetite loss, nausea and vomiting, constipation, delayed diarrhea, and amount of loperamide used.
• Dose intensity and response were recorded.
• Use of loperamide was recorded. Patients received 2 mg loperamide on demand after every diarrheal episode. When this approach did not succeed, patients were managed with 2 mg of loperamide every 4 hours routinely until free of diarrhea for 12 hours.

• European Cooperative Oncology Group (ECOG) Common Toxicity Criteria (CTC) were measured.
• The OA and CD group (group B) had the following results.
  • Higher stool pH (p < 0.0001)
  • Reduced incidence of delayed diarrhea at grade 2 or higher (group A = 32.3%, group B = 9.4%, p = 0.005)
  • Nausea (p = 0.0001)
  • Vomiting (p = 0.001)
  • Myelotoxicity (p = 0.03)
  • Lymphocytopenia (p = 0.034)
  • Dose intensification (from 34.6 to 39.9 mg/m² per week [p < 0.001])
  • Tumor response rate of 59.3% versus 38.5% in group A (p = 0.173).
• Duration of delayed diarrhea was 2.8 times longer in group A (p < 0.0001).
• Loperamide use was greater in group A (p = 0.003).

Patient response rates did not indicate that OA and CD compromised the clinical efficacy of irinotecan and cisplatin therapy. Although a reduced amount of irinotecan and SN-38 may be circulated enterohepatically, the increased dose intensity conferred by OA and CD resulted in maintenance of the same degree of clinical efficacy.

OA and CD appeared to be useful in preventing the dose-limiting side effects of irinotecan, primarily nausea, vomiting, granulocytopenia, and delayed diarrhea.

To evaluate the efficacy of palonosetron plus dexamethasone in controlling delayed chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer receiving paclitaxel and carboplatin (a moderately emetogenic protocol)

On day 1 of therapy, palonosetron at 0.75 mg/body IV and dexamethasone at 19.8 mg/body IV were administered. On days 2 and 3, dexamethasone at 6.6 mg/body in 100 ml of normal saline IV was given. Patients were administered the Multinational Association of Supportive Care in Cancer Antiemesis Tool to complete on days 1–8. Only the first cycle of this protocol was evaluated. The patients rated the intensity of nausea using a Visual Analog Scale scored as mild (1–2), moderate (3–4), or severe (≥ 5).

• N = 42
• MEDIAN AGE = 60.5 years (range = 32–83 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Gynecologic cancers including cervical, endometrial, and ovarian
• OTHER KEY SAMPLE CHARACTERISTICS: Naïve to chemotherapy; aged ≥ 20 years; receiving a regimen of paclitaxel and carboplatin every three weeks; Eastern Cooperative Oncology Group performance status of 0–2; laboratory results related to bone marrow and hepatic and renal functions met criteria for chemotherapy infusion

• SITE: Not stated 
• SETTING TYPE: Not specified  
• LOCATION: Japan

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

Phase 2, nonrandomized, prospective, nonblinded clinical trial

• Self-completion of the Multinational Association of Supportive Care in Cancer (MASCC) antiemesis tool
• Visual Analog Scale (VAS) to measure intensity of nausea
• Complete response (CR) was defined as no vomiting, no additional antiemetic use, and no rescue therapy.  
• Complete control (CC) was defined as complete control of vomiting with no antiemetic use, only mild nausea, and no rescue therapy.
• Subgroup analyses were performed to comparatively assess the delayed CR rates by age (≥ 55 years versus < 55 years), body surface area (≥ 1.47 m² versus < 1.47 m²), performance status (0 versus 1–2), and complications (present versus absent).

The CR rate for the acute period (0–24 hours) was 95.2%, or 40 out of 42 patients. In the delayed period (24–96 hours), a CR of 90.5%, or 38 out of 42 patients, was reported. Overall, the CR rate was 85.7%, or 36 out of 42 patients. The CC rate for the acute period was 90.5%, or 38 out of 42 patients. For the delayed period, it was 85.7%, or 36 out of 42 patients. The CC rate was 78.6%, or 33 out of 42, overall. Nausea was reported in the acute, delayed, and overall periods by four, seven, and nine patients respectively. The average overall nausea score for the nine patients who reported nausea was 3.69+ 2.77 on a five-point VAS scale. Rescue antiemetics were used by two patients in the acute phase, four patients in the delayed phase, and in six patients overall. Granisetron and dexamethasone were the most commonly used rescue antiemetics. Adverse events were minimal with 16 patients experiencing constipation, three headache, and two diarrhea.

This trial supported the use of palonosetron over other 5HT3 receptor antagonists for the prevention of CINV in the 24–96-hour period following therapy in female patients with gynecologic malignancies. These data also support evidence that it is difficult to achieve CR for nausea as nine (20%) of the patients in this study experienced nausea.

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

Palonosetron was especially helpful in the prevention of CINV during the delayed phase of moderately emetogenic chemotherapy. This study also measured nausea, which was helpful because many studies primarily address vomiting even though nausea often creates more patient distress.

To determine whether early induction of low-dose opioid for the treatment of mild pain improves dietary and caloric intake and reduces weight loss among patients with head and neck cancer

The low-dose opioid this study used was controlled-release oxycodone (CRO). The intial dose was 10 mg and the dose was titrated upward as needed. Because all patients agreed to use an opioid at some point, patients were classified into two groups, mild and moderate (referring to pain), according to when the opioid was introduced.

• The sample was composed of 43 patients, 23 in the mild-pain group and 20 in the moderate-pain group.
• In the mild group, mean patient age was 63.6 years. In the moderate group, mean patient age was 63.7 years.
• In the mild group, 2 patients were female and 21 patients were male. In the moderate group, 2 patients were female and 18 were male.
• All patients had head and ceck cancers and were receiving radiation therapy from 40 Gy to a high of 60 Gy. (Not all patients received the highest dose.)

• Single site
• Inpatient
• Department of Otorhinolaryngology, Fukuoka University Hospital, Fukuoka, Japan

Prospective descriptive study

• Visual analog scale (VAS) (0 = no pain, 100 = unbearable pain), to measure pain
• Caloric intake – caloric intake rate (Caloric intake rate was calculated by dividing the caloric intake by the basal energy expenditure [BEE]. Caloric intake was estimated from inpatient dietary forms and from what patients actually ate.)
• Weight loss
• Duration of time on a regular diet before the switch to a softer or liquid diet

• VAS pain scores were significantly lower in the mild group than in the moderate group, at 25–50 Gy.
• The amount of oxycodone used for pain was significantly lower in the mild group than in the moderate group.
• Patients in the mild group maintained a regular diet for a significantly longer period than did patients in the moderate group.
• Caloric intake was significantly higher in the mild group, at more than 20 Gy.
• Weight loss was significantly lower in the mild group, at more than 20 Gy.
• The incidence of side effects was equal in both groups. Constipation and nausea were the most frequent side effects, followed by sleepiness, diarrhea, vomiting, itching, and dysuria.

Results indicated that the introduction of opioids for mild pain during radiotherapy controls the level of pain and increases the food intake of head and neck cancer patients. For such patients, use of opioids, beginning when pain is mild, may help to ensure a better dietary intake during radiotherapy.

• The study had a small sample, with fewer than 100 patients.
• Researchers took almost four years to gather data.
• The validity of the caloric-intake measures, based on what patients may have eaten, is questionable.

For the population of patients with head and neck cancer, maintaining food intake is a challenge, so this study is relevant. The intervention uses a standard pain control agent; the point at issue is the advisability of early intervention (early in terms of the World Health Organization ladder). The patient population pertinent to the study is very specific; the study is not generalizable.